Synthesis of Functionalized Indolines and Dihydrobenzofurans by Iron and Copper Catalyzed Aryl C−N and C−O Bond Formation

Martyn C. Henry, Hans Martin Senn, and Andrew Sutherland*
WestCHEM, School of Chemistry, The Joseph Black Building, University of Glasgow, Glasgow G12 8QQ, United Kingdom

INTRODUCTION
Indoline and dihydrobenzofuran scaffolds are privileged structures, represented in a wide range of natural products and pharmaceutically important agents.1 For this reason, considerable efforts have focused on the discovery of efficient methods for the preparation of these heterocycles.2 A commonly used approach for the synthesis of indolines and dihydrobenzofurans is the Buchwald−Hartwig or Ullmanntype C−N and C−O bond forming process of prefunctionalized, halogenated phenylethylamines and phenylethylalcohols (Figure 1a).3−6 As well as five-membered rings, this strategy is highly effective for the preparation of six-membered benzofused heterocyclic systems and has been used for the preparation of a wide range of natural products such as (+)-isatisine A,4g corsifuran A,5b and a number of quinolinecontaining alkaloids.

 

An alternative approach for preparing these ring systems has been developed more recently involving transition-metalcatalyzed aryl C−H activation and intramolecular crosscoupling with N−H or O−H bonds.7,8 Pioneering work by the Yu group showed that triflimide-protected 2-phenylethylamines and Pd(II)/Cu(I) catalysis could be used for the onepot preparation of indolines via a tandem C−H bond
iodination−amination sequence.8a The palladium-catalyzed intramolecular aryl C(sp2)−H amination process was improved using N-chelating groups and oxidizing agents such as hypervalent iodonium salts.8−10 Among the range of Nprotected amides used to direct the palladium-catalyzed functionalization of aryl C−H bonds, the Zhao group demonstrated the highly effective use of a N,O-bidentate
oxalyl amide (Figure 1b).8g

 

Although this strategy has also been used to prepare dihydrobenzofurans from phenylethylalcohols, the oxidizing conditions can be problematic for substrates bearing primary and secondary alcohols.11 More recently, Zakarian and coworkers reported a mechanistically distinct approach for the preparation of dihydrobenzofurans (Figure 1c).12 A one-pot intramolecular aryl C−O bond forming process was achieved by formation of nonsymmetrical diaryliodonium salts by oxidation of electron-rich 2-phenylethylalcohols, followed by a copper-catalyzed C−O bond forming process. A key feature of this method was the room temperature conditions for copper-catalyzed cyclization.

 

While these methods provide an attractive entry to these ring systems, many of the approaches have been specifically developed for either C−N or C−O bond formation or for the preparation of a particular ring size. We were interested in developing a new approach for intramolecular C−N or C−O bond formation that would avoid a prefunctionalization step, precious transition metals, strong oxidizing conditions and could be used for the general preparation of both five- and sixmembered heterocyclic systems. Herein, we describe a one-pot intramolecular C−N and C−O bond forming process that utilizes a highly regioselective iron-catalyzed iodination for initial arene activation, followed by a copper-catalyzed C−N and C−O cyclization (Figure 1d). As well as providing an electronic rationale for the high regioselectivity of the ironcatalyzed halogenation reaction, we show the general application of this process for the preparation of a wide range of ring systems and as the key step for the total synthesis
of the natural product, (+)-obtusafuran.

 

RESULTS AND DISCUSSION
Previously, we have shown that the combination of iron(III) chloride and the inexpensive ionic liquid [BMIM]NTf2 results in the formation of iron triflimide, which can be used as a super Lewis acid catalyst13 to activate N-halosuccinimides for the fast and efficient regioselective halogenation of aromatic compounds.14 In this current study, this transformation was investigated for the regioselective iodination of a new class of substrate, N-protected 2-phenylethylamines (Scheme 1). The initial aim was to evaluate the 3-methoxy substituent as a directing group for selective para-iodination and assess if the resulting activated aryl intermediate could undergo a copper-(I)-catalyzed N-arylation reaction for the one-pot synthesis of indolines. Using standard conditions for halogenation with iron(III) chloride (2.5 mol %) and [BMIM]NTf2 (7.5 mol %), the iodination of N-benzoyl protected 1a by N-iodosuccinimide (NIS) was complete in 5 h at 40 °C.14a,15 Analysis of the crude reaction mixture by 1H NMR spectroscopy showed the formation of the para-iodinated regioisomer as the sole product. The aryl ring of 1a can undergo iodination with NIS, without the iron(III) triflimide catalyst; however, under the same conditions, full conversion was only achieved after 22h giving a 10:1 mixture of para- and ortho-regioisomers. The regioselective iron(III) triflimide catalyzed activation of 1a was then performed in combination with a Cu(I)-catalyzed Narylation for the one-pot synthesis of indoline 2a. Using copper iodide (10 mol %) and DMEDA (20 mol %) during the C−N bond forming step gave N-benzoyl-protected indoline 2a in 79% overall yield. It should be noted that when the synthesis of 2a was done by performing each step separately, the overall yield (59%) was significantly lower than that for the one-pot process. With the success of the one-pot synthesis of 2a, a range of N-protecting groups were explored to evaluate the most suitable nucleophile for the Cu(I)-catalyzed N-arylation.

 

While N-Cbz and N-Boc carbamate protected indolines 2c and 2d were prepared in good yields, the most efficient one-pot processes involved N-acetamide or N-sulfonamide protected compounds. In particular, one-pot activation and cyclization of N-tosyl phenylethylamine 1f gave indoline 2f in 93% yield. Having identified optimized conditions and the most efficient N-nucleophile, the scope of the one-pot activation and cyclization process was explored for the preparation of indolines (Scheme 2). Using a range of N-tosyl ethylamine substituted anisoles, anilines, and acetanilides gave the corresponding indolines 2f−2o as single regioisomers, in 43−93% yields.16 As expected, substrates with multiple activating groups were converted to the indolines in shorter overall reaction times. Interestingly, phenylethylamine 1o containing N-acetyl and chlorine substituents failed to undergo the iron(III)-catalyzed iodination even at 70 °C. Instead, activation was achieved by bromination using N bromosuccinimide (NBS) at 40 °C. Completion of the one-pot process gave indoline 2o in 43% yield. Access to other benzannulated heterocycles was also achieved using the one-pot process.

 

Iron(III)-catalyzed iodination and copper(I)-catalyzed cyclization of 3-methoxyphenylacetamide (1p) gave 2-oxindole 2p in 65% yield, while an N-tosyl propylamine substituted anisole led to the corresponding tetrahydroquinoline 2q in 85% yield. The use of palladium-catalyzed C−H activation in the presence of phenyliodonium diacetate, followed by C−O cyclization for the synthesis of dihydrobenzofurans, can be done using tertiary11a or secondary benzylic alcohol nucleophiles.11b However, the general use of substrates bearing primary or secondary hydroxy groups for this process are
problematic due to competitive oxidation.12 Mild oxidative conditions such as those reported by the Zakarian group are required for general access to dihydrobenzofurans (Figure 1c).12 Following the successful application of the one-pot iron(III)-catalyzed activation and copper(I)-catalyzed cyclization for the synthesis of N-heterocycles, we were interested to discover whether the mild oxidative conditions for this twostep process could also be applied for the preparation of dihydrobenzofurans. The transformation was initially attempted using 3-methoxyphenylethan-2′-ol (3a) for the synthesis of
2,3-dihydro-5-methoxybenzofuran (4a) (Scheme 3). While the standard iodination conditions could be used, a slightly higher temperature (150 °C) was required for complete conversion to the cyclized dihydrobenzofuran. This gave 4a in 65% yield.

 

The scope of this process was then explored using a range of substrates with various aryl activating groups and primary, secondary, or tertiary alcohol nucleophiles (3a−3i). In general, the one-pot processes were performed under the standard conditions developed for the N-heterocycles, giving the corresponding dihydrobenzofurans as single regioisomers in 56−72% yields. It should be noted that while other one-pot methods have had problems with overoxidation and the generation of benzofuran byproducts, especially with electronrich substrates,11b analogous dihydrobenzofurans produced in this study (e.g., 4b−4d) were formed cleanly as single products. The only limitation was found during the synthesis of natural product corsifuran A (4g).18 Substrate 3g, which contains two activated aryl rings, gave a mixture of products during the iodination step, resulting in the isolation of corsifuran A (4g) in only 29% yield.19 However, using secondary benzylic alcohols with less electron-rich aryl rings (e.g., 3h and 3i) allowed selective iodination of the 3-methoxyphenyl moiety resulting in the synthesis of dihydrobenzofurans 4h and 4i in 64% and 63% yields, respectively.

 

This approach was also effective for the one-pot synthesis of dihydrobenzopyrans. Application of (3-methoxyphenyl)-propan-3′-ol (3j) to the one-pot iron(III)-catalyzed activation and copper(I)-catalyzed cyclization gave dihydrobenzopyran 4j as the sole product in 57% yield. Similar results were also obtained for dihydrobenzopyrans 4k and 4l.

 

To further explore the functional group tolerance of the onepot process and illustrate its application for natural product synthesis, the method was investigated as a key step for the total synthesis of (+)-obtusafuran (10). The neolignan (+)-obtusafuran was first isolated from the heartwood of Dalbergia retusa20 and more recently from several other Dalbergia species.21−23 As well as possessing antiplasmodial activity,21 (+)-obtusafuran has been shown to have anticarcinogenic activity as a potent inducer of the carcinogendetoxifying enzyme, quinone reductase.24 Racemic obtusafuran has been prepared by a thermal rearrangement of the neoflavanoid, obtusaquinol,25 while the only asymmetric synthesis of (+)-obtusafuran was reported by Chen and Weisel, who used an enantioselective hydrogenation to produce a chiral alcohol that was then subjected to an SNAr reaction to form the furan ring.26 Our strategy involved the synthesis of α-methyl phenyl ketone 7 (Scheme 4) and the application of this to a Merck-type enantioselective hydrogenation involving a base-mediated dynamic kinetic resolution process.27,28 The resulting secondary benzylic alcohol 8 would then be used in the one-pot iron(III)-catalyzed iodination and copper(I)-catalyzed cyclization to complete the synthesis of the dihydrobenzofuran skeleton. Initially, Weinreb amide 6 was prepared in two steps from phenylacetic acid 5, by coupling with N,O-dimethylhydroxylamine using EDCI and HOBt, followed by TBDMS protection of the phenol under standard conditions. Reaction of 6 with phenylmagnesium bromide and then α-alkylation with LiHMDS and methyl iodide gave key intermediate 7 in good overall yield. This was then subjected to the Merck enantioselective hydrogenation using the commercially available Noyori-type chiral catalyst, RuCl2[(S)-DM-Segphos][(S)-DAIPEN].27−29 On screening various conditions and catalyst loadings, the best results were achieved by hydrogenation at 10 bar of pressure, using 2 mol % of the Ru(II)-catalyst. This gave secondary alcohol 8 as a single diastereomer, in 95% enantiomeric excess and 64% yield.30 Our one-pot process was then investigated for the final key step. Activation of the aryl ring using the iron(III)-catalyzed iodination required a slightly higher temperature (50 °C) and longer reaction time (7 h) than the more simple substrates.

 

Following this step, the standard conditions of the copper(I)-catalyzed cyclization were then used to complete the one-pot process, which gave dihydrobenzofuran 9 in 63% yield. Despite using a substrate with a highly activated aryl ring and a secondary alcohol, no byproducts from overiodination or oxidation were observed at either stage of the one-pot process.

 

 

Finally, TBAF mediated removal of the silyl protecting group completed the eight-step synthesis of (+)-obtusafuran (10) in 16% overall yield. The spectroscopic data and optical rotation of 10 were entirely consistent with literature data.20b,26 Iron(III)-catalyzed activation of the N-protected 2-phenylethylamines and phenylethan-2′-ols gave the para-iodinated isomers as the sole product. As no reaction was observed at the other activated positions, including the most sterically accessible ortho-position, DFT calculations were used to explore electronic reasons for this reactivity.31 The reactivities of different sites toward electrophilic or nucleophilic attack may be assessed using a computed descriptor such as partial (atomic) charge. In this study, the Hirshfeld partitioning scheme was used.32 The Hirshfeld charges calculated for the (unsubstituted) aromatic carbons of N-mesyl protected 2-phenylethylamine 1e single out C-5 as the least preferred site for electrophilic attack, but cannot distinguish which of C-2, C-4, or C-6 would be the most preferred site (Table 1, entry 1).

 

A more refined and powerful reactivity descriptor is provided by the Fukui functions.33,34 The electrophilic Fukui function f −(r) has more positive values at points in space where it is energetically favorable to remove electrons (see Supporting Information for background and derivations); that is, f −(r) identifies sites favored for electrophilic attack. If the reactivity is entirely controlled by the frontier orbitals, f −(r) is well approximated by the density of the HOMO. From Figure 2, it is evident that the most positive region of f −(r), and hence the most favorable site for electrophilic attack of 1e, is located around C-6.

 

More specifically, the pz atomic orbital on C-6 makes the largest contribution to the HOMO. By contracting the continuous Fukui functions to distinct sites (e.g., atoms),“condensed” Fukui reactivity indices are obtained; a large (positive) electrophilicity index f − indicates a favored site for electrophilic attack. Using frontier-orbital terminology, f − for a particular atom can be identified with the contribution of that atom to the HOMO. f − values for the aromatic carbons in 1e are presented in Table 1 (entries 2 and 3). The quantitative reactivity analysis using atomic Fukui indices thus clearly identifies C-6 as the most preferred site for electrophilic attack in this case, in agreement with experiment. C-2 and C-4 have significantly diminished, nearly equal reactivity; C-5 is predicted to be least reactive. Further analysis can be performed using a “dual descriptor” Δf, which combines the separate electrophilic and nucleophilic Fukui functions into one descriptor.35 More positive values of Δf indicate sites for nucleophilic attack; more negative values indicate sites for electrophilic attack. As can be seen from Table 1 (entries 4 and 5), the analysis based on Δf values fully confirms the regioselectivity observed for activation of the substrates in this study.

 

CONCLUSIONS
In summary, a one-pot, two-step method involving iron(III)-catalyzed aryl ring activation and copper(I)-catalyzed C−N or C−O bond forming cyclization has been developed for the general synthesis of valuable N- and O-heterocyclic scaffolds.

Following DFT calculations, which showed the molecular orbital basis for the highly regioselective halogenation step, the novel, one-pot method was applied to the efficient synthesis of indolines and dihydrobenzofurans, as well as six-membered analogues. This one-pot approach does not require prefunctionalization of the substrate as with the traditional Buchwald−Hartwig and Ullmann-type intramolecular couplings, and unlike the established palladium-catalyzed dehydrogenative processes, this method has no issues with overiodination or oxidation and could be applied to substrates with highly activated aryl ring systems and with primary and secondary alcohols. This was exemplified by the use of this one-pot process as the key step for the total synthesis of the neolignan natural product, (+)-obtusafuran. We expect this simple and effective approach to find utilization in the preparation of other heterocyclic scaffolds and for application in the synthesis of natural products and medicinal chemistry targets. Investigation of further applications of the one-pot process is currently underway.

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4-(2,3-dichlorophenoxy)benzoic acid Catalog No.:AA01AKNR CAS No.:1040084-01-2 MDL No.:MFCD11522266 MF:C13H8Cl2O3 MW:283.1068	3-{[(4-fluorophenyl)sulfanyl]methyl}-1-benzofuran-2-carboxylic acid Catalog No.:AA019Y10 CAS No.:1040084-06-7 MDL No.:MFCD13378778 MF:C16H11FO3S MW:302.3201
2-[5-(METHYLSULFAMOYL)THIOPHEN-2-YL]ACETIC ACID Catalog No.:AA01EMRH CAS No.:1040084-18-1 MDL No.:MFCD11124780 MF:C7H9NO4S2 MW:235.2807	2-chloro-1-N-(1-phenylethyl)benzene-1,4-diamine Catalog No.:AA019WNM CAS No.:1040084-84-1 MDL No.:MFCD11187007 MF:C14H15ClN2 MW:246.7353
Di-Norbudesonide (Mixture of DiastereoMers) Catalog No.:AA00962R CAS No.:1040085-98-0 MDL No.:MFCD24386588 MF:C23H30O6 MW:402.4807	16a,17-[(1RS)-Butylidenebis(oxy)]-11b-hydroxy-17-(hydroxymethyl)-D-homoandrosta-1,4-diene-3,17a-dione Catalog No.:AA008WXI CAS No.:1040085-99-1 MDL No.:MFCD29920082 MF:C25H34O6 MW:430.5339
3-Hydroxyphenylacetylene Catalog No.:AA003JC3 CAS No.:10401-11-3 MDL No.:MFCD00078347 MF:C8H6O MW:118.1326	2-Bromo-3-methoxybenzaldehyde Catalog No.:AA007F4U CAS No.:10401-18-0 MDL No.:MFCD09834663 MF:C8H7BrO2 MW:215.0440
sodium (6R,7R)-7-[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetamido]-3-{[(furan-2-yl)carbonylsulfanyl]methyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Catalog No.:AA008531 CAS No.:104010-37-9 MDL No.:MFCD01766184 MF:C19H16N5NaO7S3 MW:545.5444	(+)-(3As,6as)-3a,6a-dihydro-2,2-dimethyl-4h-cyclopenta-1,3-dioxol-4-one Catalog No.:AA008UMC CAS No.:104010-72-2 MDL No.:MFCD08166478 MF:C8H10O3 MW:154.1632
3-Bromo-1h-indazole-7-carboxylic acid Catalog No.:AA00389S CAS No.:1040101-01-6 MDL No.:MFCD11977526 MF:C8H5BrN2O2 MW:241.0415	O-(D-Glucopyranosylidene)amino N-Phenylcarbamate Catalog No.:AA00852Z CAS No.:104012-84-2 MDL No.:MFCD00145030 MF:C13H16N2O7 MW:312.2753
1,2,4,6-Tetra-O-acetyl-3-chloro-3-deoxy-D-glucopyranose Catalog No.:AA008SKV CAS No.:104013-04-9 MDL No.:MFCD03425532 MF:C14H19ClO9 MW:366.7483	(1S)-1-(4-iodophenyl)ethan-1-ol Catalog No.:AA01AGMP CAS No.:104013-25-4 MDL No.:MFCD09863731 MF:C8H9IO MW:248.0609
1-[4-(methylsulfanyl)phenyl]imidazolidin-2-one Catalog No.:AA00IZDX CAS No.:1040130-00-4 MDL No.:MFCD11501856 MF:C10H12N2OS MW:208.2801	1-benzylpyrrolidin-3-yl methanesulfonate Catalog No.:AA01ACC4 CAS No.:104016-82-2 MDL No.:MFCD20487884 MF:C12H17NO3S MW:255.3333
1-(1H-Indol-7-yl)-ethanone Catalog No.:AA009NKV CAS No.:104019-20-7 MDL No.:MFCD12924119 MF:C10H9NO MW:159.1846	3-[4-(2-ethoxy-2-phenylethyl)piperazin-1-yl]-2-methyl-1-phenylpropan-1-one dihydrochloride Catalog No.:AA007F1N CAS No.:10402-53-6 MDL No.:MFCD01695215 MF:C24H34Cl2N2O2 MW:453.4450
2,2-Dichloro-1-(4-ethoxyphenyl)cyclopropanecarboxylic acid Catalog No.:AA007F1Q CAS No.:104023-75-8 MDL No.:MFCD13185936 MF:C12H12Cl2O3 MW:275.1279	[(3S)-4'-[(4S)-4-benzyl-4,5-dihydro-1,3-oxazol-2-yl]-3,3'-spirobi[1,2-dihydroindene]-4-yl]-bis(3,5-ditert-butylphenyl)phosphane Catalog No.:AA008V82 CAS No.:1040274-10-9 MDL No.:MFCD17018765 MF:C55H66NOP MW:788.0924
(Sa,S)-DTB-Ph-SIPHOX Catalog No.:AA01DH57 CAS No.:1040274-12-1 MDL No.:MFCD31807293 MF:C54H64NOP MW:774.0658	2-[(1S)-7'-[Bis[3,5-bis(1,1-dimethylethyl)phenyl]phosphino]-2,2',3,3'-tetrahydro-1,1'-spirobi[1H-inden]-7-yl]-4,5-dihydrooxazole Catalog No.:AA00392O CAS No.:1040274-18-7 MDL No.:MFCD21362521 MF:C48H60NOP MW:697.9699
(2S)-3-(4-bromophenyl)-2-methylpropanoic acid Catalog No.:AA00J064 CAS No.:1040274-42-7 MDL No.:MFCD29126453 MF:C10H11BrO2 MW:243.0971	1-BOC-4-bromo-3,5-dimethylpyrazole Catalog No.:AA007F1M CAS No.:1040276-87-6 MDL No.:MFCD12756451 MF:C10H15BrN2O2 MW:275.1423
5-Formyl-2-thiopheneboronic acid pinacol ester Catalog No.:AA003A1W CAS No.:1040281-83-1 MDL No.:MFCD09266186 MF:C11H15BO3S MW:238.1110	4-Chlorothiophen-2-boronic acid, pinacol ester Catalog No.:AA007WQ6 CAS No.:1040281-84-2 MDL No.:MFCD18383081 MF:C10H14BClO2S MW:244.5460
4-Acetylthiophene-2-boronic acid, pinacol ester Catalog No.:AA007F1L CAS No.:1040281-85-3 MDL No.:MFCD12405476 MF:C12H17BO3S MW:252.1376	4-(Methoxycarbonyl)thiophene-2-boronic acid pinacol ester Catalog No.:AA008XI8 CAS No.:1040281-86-4 MDL No.:MFCD12407258 MF:C12H17BO4S MW:268.1370
2-Bromo-5-nitroaniline Catalog No.:AA008RJI CAS No.:10403-47-1 MDL No.:MFCD00051578 MF:C6H5BrN2O2 MW:217.0201	(2E)-2-(1H-1,3-benzodiazol-2-yl)-3-(thiophen-2-yl)prop-2-enenitrile Catalog No.:AA01EM1J CAS No.:104030-31-1 MDL No.:MFCD00238786 MF:C14H9N3S MW:251.3064
CARPROPAMID Catalog No.:AA008RIC CAS No.:104030-54-8 MDL No.:MFCD03095718 MF:C15H18Cl3NO MW:334.6685	N-(2-Acetylphenyl)octanamide Catalog No.:AA0099UY CAS No.:1040310-65-3 MDL No.:MFCD12558265 MF:C16H23NO2 MW:261.3593
Methyl 2-[(3-nitropyridin-4-yl)amino]acetate Catalog No.:AA01A5Q7 CAS No.:1040313-67-4 MDL No.:MFCD11184501 MF:C8H9N3O4 MW:211.1748	4-(2-Bromophenoxymethyl)-1,2-dichlorobenzene Catalog No.:AA007F1F CAS No.:1040313-76-5 MDL No.:MFCD07782657 MF:C13H9BrCl2O MW:332.0200
4-(2-methyl-1H-imidazol-1-yl)pyridin-3-amine Catalog No.:AA01AI90 CAS No.:1040314-53-1 MDL No.:MFCD11184550 MF:C9H10N4 MW:174.2025	3-aMino-4-benzyloxypyridine Catalog No.:AA00988Q CAS No.:1040314-69-9 MDL No.:MFCD11184559 MF:C12H12N2O MW:200.2365
N-methyl-2,3-dihydro-1H-indene-5-sulfonamide Catalog No.:AA01EI8D CAS No.:1040316-70-8 MDL No.:MFCD11174504 MF:C10H13NO2S MW:211.2807	4-(5,6,7,8-Tetrahydro-[1,2,4]triazolo[4,3-a]pyridin-3-yl)aniline Catalog No.:AA00JFV7 CAS No.:1040326-79-1 MDL No.:MFCD11184217 MF:C12H14N4 MW:214.2664
4-{5H,6H,7H,8H-[1,2,4]triazolo[4,3-a]pyridin-3-yl}phenol Catalog No.:AA01BD46 CAS No.:1040326-87-1 MDL No.:MFCD11184221 MF:C12H13N3O MW:215.2511	{3-[(5-bromopyridin-2-yl)amino]-2,2-dimethylpropyl}dimethylamine Catalog No.:AA01BHKA CAS No.:1040328-99-1 MDL No.:MFCD11125301 MF:C12H20BrN3 MW:286.2113
4-chloro-2-[3-(2-methylpropyl)-1,2,4-oxadiazol-5-yl]aniline Catalog No.:AA019YSR CAS No.:1040329-41-6 MDL No.:MFCD11125528 MF:C12H14ClN3O MW:251.7121	N-(3-ethoxypropyl)-2-nitroaniline Catalog No.:AA019EWI CAS No.:1040329-50-7 MDL No.:MFCD11123708 MF:C11H16N2O3 MW:224.2563
5-(1-chloroethyl)-3-cyclopropyl-1,2,4-oxadiazole Catalog No.:AA018RTK CAS No.:1040329-60-9 MDL No.:MFCD12912724 MF:C7H9ClN2O MW:172.6122	(4-Isopropoxyphenyl)hydrazine hydrochloride Catalog No.:AA00852I CAS No.:104033-62-7 MDL No.:MFCD06738787 MF:C9H15ClN2O MW:202.6812
2-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-4-fluoroaniline Catalog No.:AA019TDX CAS No.:1040333-74-1 MDL No.:MFCD11120780 MF:C11H10FN3O MW:219.2150	2-amino-N-(2,3-dihydro-1,4-benzodioxin-6-yl)benzene-1-sulfonamide Catalog No.:AA01B1IO CAS No.:1040334-54-0 MDL No.:MFCD13367348 MF:C14H14N2O4S MW:306.3370
5-[(carbamoylmethyl)sulfamoyl]-2-chlorobenzoic acid Catalog No.:AA01BV00 CAS No.:1040335-21-4 MDL No.:MFCD11521947 MF:C9H9ClN2O5S MW:292.6962	2-Methyl-5-(3-methyl-1,2,4-oxadiazol-5-yl)aniline Catalog No.:AA00HA6X CAS No.:1040336-24-0 MDL No.:MFCD11121026 MF:C10H11N3O MW:189.2138
4-chloro-2-(3-ethyl-1,2,4-oxadiazol-5-yl)aniline Catalog No.:AA019YSW CAS No.:1040345-45-6 MDL No.:MFCD11119587 MF:C10H10ClN3O MW:223.6589	4-[(4-hydroxypiperidin-1-yl)methyl]benzoic acid Catalog No.:AA019VWX CAS No.:1040346-47-1 MDL No.:MFCD11123540 MF:C13H17NO3 MW:235.2790
5-[(4-fluorophenyl)methoxy]-4-oxo-4H-pyran-2-carboxylic acid Catalog No.:AA01ARBD CAS No.:1040348-99-9 MDL No.:MFCD16171006 MF:C13H9FO5 MW:264.2060	Acetamidine Hydrobromide Catalog No.:AA01FN8Y CAS No.:1040352-82-6 MDL No.:MFCD32062852 MF:C2H7BrN2 MW:138.9944
methyl 2-cyclohexyl-2-methoxyacetate Catalog No.:AA01B5EQ CAS No.:104036-61-5 MDL No.:MFCD30342590 MF:C10H18O3 MW:186.2481	2-(Quinolin-2-yl)ethanamine Catalog No.:AA007F1C CAS No.:104037-38-9 MDL No.:MFCD08448930 MF:C11H12N2 MW:172.2264
4-Bromo-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole Catalog No.:AA008S00 CAS No.:1040377-02-3 MDL No.:MFCD11505042 MF:C8H11BrN2O MW:231.0897	1-(Tetrahydro-pyran-4-yl)-1H-pyrazole-4-boronic acid pinacol ester Catalog No.:AA00389R CAS No.:1040377-03-4 MDL No.:MFCD12033229 MF:C14H23BN2O3 MW:278.1550
1-(2-Hydroxyethyl)-1h-pyrazole-4-boronic acid pinacol ester Catalog No.:AA007WPM CAS No.:1040377-08-9 MDL No.:MFCD12033564 MF:C11H19BN2O3 MW:238.0912	4-Bromo-2-morpholinopyridine Catalog No.:AA00852F CAS No.:1040377-12-5 MDL No.:MFCD13195616 MF:C9H11BrN2O MW:243.1004
2-Methyl-2-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1h-pyrazol-1-yl]propan-1-ol Catalog No.:AA003A3I CAS No.:1040377-18-1 MDL No.:MFCD22571853 MF:C13H23BN2O3 MW:266.1443	2-Naphthalenecarboxamide, 3-hydroxy-N-(phenylmethyl)- Catalog No.:AA00HA72 CAS No.:104040-43-9 MDL No.:MFCD00578855 MF:C18H15NO2 MW:277.3172
3-(Trifluoromethyl)pyridine-2-thiol Catalog No.:AA003I7T CAS No.:104040-74-6 MDL No.:MFCD00178749 MF:C6H4F3NS MW:179.1629	3-(Trifluoromethyl)pyridine-2-sulfonyl chloride Catalog No.:AA0095JX CAS No.:104040-75-7 MDL No.:MFCD16093662 MF:C6H3ClF3NO2S MW:245.6067
Flazasulfuron Catalog No.:AA007F1A CAS No.:104040-78-0 MDL No.:MFCD00274594 MF:C13H12F3N5O5S MW:407.3251	2-Amino-5-fluorophenylboronic acid Catalog No.:AA007WPK CAS No.:1040400-87-0 MDL No.:MFCD03095362 MF:C6H7BFNO2 MW:154.9347
4-Mercaptomethyl Dipicolinic Acid Catalog No.:AA008W4Z CAS No.:1040401-18-0 MDL No.:MFCD16293855 MF:C8H7NO4S MW:213.2105	4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]benzaldehyde Catalog No.:AA00990L CAS No.:1040424-52-9 MDL No.:MFCD18447531 MF:C19H21BO3 MW:308.1792
4-(4-Ethoxyphenyl)-1H-pyrazol-5-amine Catalog No.:AA00J3T2 CAS No.:1040454-88-3 MDL No.:MFCD04220310 MF:C11H13N3O MW:203.2404	4-(Trifluoromethyl)pyrimidin-2(1h)-one Catalog No.:AA003HBG CAS No.:104048-92-2 MDL No.:MFCD00192529 MF:C5H3F3N2O MW:164.0853
Trospium chloride Catalog No.:AA007EZN CAS No.:10405-02-4 MDL No.:MFCD00865254 MF:C25H30ClNO3 MW:427.9636	2-Aminobutane-1,4-diol Catalog No.:AA007WPG CAS No.:10405-07-9 MDL No.:MFCD09863824 MF:C4H11NO2 MW:105.1356
LP-533401 HCl Catalog No.:AA0095XI CAS No.:1040526-12-2 MDL No.:MFCD18803629 MF:C27H23ClF4N4O3 MW:562.9431	Atipamezole Catalog No.:AA008R9F CAS No.:104054-27-5 MDL No.:MFCD00864502 MF:C14H16N2 MW:212.2902
Boc-aib-osu Catalog No.:AA00912E CAS No.:104055-39-2 MDL No.:MFCD00672711 MF:C9H17NO7S MW:283.2988	H-D-Ser-OEt HCl Catalog No.:AA008ULJ CAS No.:104055-46-1 MDL No.:MFCD00191020 MF:C5H12ClNO3 MW:169.6067
5-Chloroindole-3-carboxylic acid Catalog No.:AA007EZG CAS No.:10406-05-0 MDL No.:MFCD03410308 MF:C9H6ClNO2 MW:195.6024	5-Bromo-1H-indole-3-carboxylic acid Catalog No.:AA003MCU CAS No.:10406-06-1 MDL No.:MFCD05664007 MF:C9H6BrNO2 MW:240.0534
3-Cyanobenzylamine Catalog No.:AA003J9H CAS No.:10406-24-3 MDL No.:MFCD06797832 MF:C8H8N2 MW:132.1625	4-Cyanobenzylamine Catalog No.:AA00HA75 CAS No.:10406-25-4 MDL No.:MFCD00025578 MF:C8H8N2 MW:132.1625
5-((3aS,4S,5S,6aR)-5-Oxido-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanoic acid Catalog No.:AA007WP6 CAS No.:10406-89-0 MDL No.:MFCD00005541 MF:C10H16N2O4S MW:260.3100	N-Boc-2-(4-aminophenyl)ethanol Catalog No.:AA008527 CAS No.:104060-23-3 MDL No.:MFCD04974330 MF:C13H19NO3 MW:237.2949
Carbamic acid, [(1S)-1-formylpentyl]-, 1,1-dimethylethyl ester Catalog No.:AA007EZE CAS No.:104062-70-6 MDL No.:MFCD09802282 MF:C11H21NO3 MW:215.2893	(2-[(PYRIDIN-4-YLMETHYL)THIO]-1,3-THIAZOL-4-YL)ACETIC ACID Catalog No.:AA01AREU CAS No.:1040631-48-8 MDL No.:MFCD11007753 MF:C11H10N2O2S2 MW:266.3393
2-Amino-N-methyl-5,6-dihydro-4H-cyclopenta[d][1,3]thiazole-4-carboxamide Catalog No.:AA01AREW CAS No.:1040631-51-3 MDL No.:MFCD11007756 MF:C8H11N3OS MW:197.2574	3-[6-(4-Methoxyphenyl)imidazo[2,1-b][1,3]thiazol-3-yl]propanoic acid Catalog No.:AA01ARF0 CAS No.:1040631-69-3 MDL No.:MFCD11007774 MF:C15H14N2O3S MW:302.3483
2-(2-Methylpropoxy)aniline Catalog No.:AA007WP9 CAS No.:104065-95-4 MDL No.:MFCD06800804 MF:C10H15NO MW:165.2322	6-Chloro-N-(3-chloro-4-methoxyphenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine Catalog No.:AA01FMNP CAS No.:1040662-49-4 MDL No.:MFCD11518857 MF:C13H11Cl2N5O MW:324.1653
6-CHLORO-N-(4-CHLORO-2-METHYLPHENYL)-1-METHYL-1H-PYRAZOLO[3,4-D]PYRIMIDIN+ Catalog No.:AA01ARI2 CAS No.:1040662-56-3 MDL No.:MFCD11518858 MF:C13H11Cl2N5 MW:308.1659	6-Chloro-1-methyl-4-piperidin-1-yl-1H-pyrazolo[3,4-d]pyrimidine Catalog No.:AA01FMLL CAS No.:1040662-63-2 MDL No.:MFCD11518860 MF:C11H14ClN5 MW:251.7154
6-Chloro-N-(3-chloro-4-methylphenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine Catalog No.:AA01FMPP CAS No.:1040662-70-1 MDL No.:MFCD11518863 MF:C13H11Cl2N5 MW:308.1659	6-Chloro-n-(3,4-dimethylphenyl)-1-methyl-1h-pyrazolo[3,4-d]pyrimidin-4-amine Catalog No.:AA01FMOH CAS No.:1040662-77-8 MDL No.:MFCD11518865 MF:C14H14ClN5 MW:287.7475
6-Chloro-N-(3-chlorophenyl)-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine Catalog No.:AA01ARHJ CAS No.:1040662-85-8 MDL No.:MFCD11518867 MF:C17H11Cl2N5 MW:356.2087	2-aminoethyl 2,6-diaminohexanoate trihydrochloride Catalog No.:AA0039HF CAS No.:104068-74-8 MDL No.:MFCD26137698 MF:C8H22Cl3N3O2 MW:298.6382
2-Fluoro-4-(trifluoromethyl)nicotinic acid Catalog No.:AA003H6I CAS No.:1040681-74-0 MDL No.:MFCD10687403 MF:C7H3F4NO2 MW:209.0978	1H-Pyrrolo[3,2-c]pyridine-4-carbonitrile Catalog No.:AA008SAH CAS No.:1040682-68-5 MDL No.:MFCD09965899 MF:C8H5N3 MW:143.1454
Methyl 1h-pyrrolo[3,2-c]pyridine-4-carboxylate Catalog No.:AA008SAK CAS No.:1040682-92-5 MDL No.:MFCD09965907 MF:C9H8N2O2 MW:176.1720	5-Chloro-1h-pyrrolo[2,3-b]pyridin-4-amine Catalog No.:AA008UUS CAS No.:1040683-00-8 MDL No.:MFCD10574984 MF:C7H6ClN3 MW:167.5956
3-Fluoro-5-(trifluoromethyl)pyridin-2-ol Catalog No.:AA008TOF CAS No.:1040683-15-5 MDL No.:MFCD10699119 MF:C6H3F4NO MW:181.0877	3-(sec-Butoxy)-N-methylaniline Catalog No.:AA009A38 CAS No.:1040686-77-8 MDL No.:MFCD10687536 MF:C11H17NO MW:179.2588
4-fluoro-2-(trifluoromethyl)benzene-1-sulfonamide Catalog No.:AA01AB52 CAS No.:1040687-55-5 MDL No.:MFCD10687237 MF:C7H5F4NO2S MW:243.1787	ethyl 3-{[(pyridin-3-yl)methyl]amino}propanoate Catalog No.:AA00JT2V CAS No.:1040688-05-8 MDL No.:MFCD10687258 MF:C11H16N2O2 MW:208.2569
N-{2-[2 Catalog No.:AA01FOAG CAS No.:1040688-35-4 MDL No.: MF:C26H39NO2 MW:397.5934	Methyl 3-[(tetrahydro-2-furanylmethyl)amino]-propanoate Catalog No.:AA0090EQ CAS No.:1040688-74-1 MDL No.:MFCD10687283 MF:C9H17NO3 MW:187.2362
3-[(2-METHOXYETHYL)AMINO]PROPANAMIDE Catalog No.:AA0090O3 CAS No.:1040689-66-4 MDL No.:MFCD10687306 MF:C6H14N2O2 MW:146.1876	3-(4-Benzhydryl-1-piperazinyl)-N-methyl-1-propanamine Catalog No.:AA01FOA6 CAS No.:1040692-41-8 MDL No.: MF:C21H29N3 MW:323.4751
5,14-dioxo-9,10-dithia-2,6,13,17-tetraazaoctadecanedioicacid,1,18-bis(phenylmethyl)ester Catalog No.:AA01EPN0 CAS No.:104071-84-3 MDL No.: MF:C26H34N4O6S2 MW:562.7014	3-(1H-INDOL-3-YL)-1H-PYRAZOL-5-AMINE Catalog No.:AA01AR8K CAS No.:1040724-73-9 MDL No.:MFCD09743154 MF:C11H10N4 MW:198.2239
tert-Butyl 5-amino-3-(4-chlorophenyl)-1h-pyrazole-1-carboxylate Catalog No.:AA00IWJH CAS No.:1040724-83-1 MDL No.:MFCD28962694 MF:C14H16ClN3O2 MW:293.7487	1-(2-iodoethenyl)pyrrolidin-2-one Catalog No.:AA01B223 CAS No.:1040743-30-3 MDL No.:MFCD30342739 MF:C6H8INO MW:237.0383