original_index int64 2 1.77M | extracted_from_file stringclasses 489 values | date_of_experiment timestamp[ns]date | grant_date timestamp[ns]date 1976-01-01 00:01:00 2016-01-01 00:09:00 | is_mapped bool 1 class | rxn_str stringlengths 87 6.12k | reactant_000 stringlengths 1 902 | reactant_001 stringlengths 1 902 ⌀ | reactant_002 null | agent_000 stringlengths 1 540 ⌀ | agent_001 stringlengths 1 852 ⌀ | agent_002 stringlengths 1 247 ⌀ | agent_003 null | agent_004 null | agent_005 null | agent_006 null | agent_007 null | agent_008 null | agent_009 null | agent_010 null | agent_011 null | agent_012 null | agent_013 null | agent_014 null | agent_015 null | agent_016 null | solvent_000 stringclasses 446 values | solvent_001 stringclasses 405 values | solvent_002 null | solvent_003 null | solvent_004 null | solvent_005 null | solvent_006 null | solvent_007 null | solvent_008 null | solvent_009 null | solvent_010 null | temperature float64 -230 30.1k ⌀ | rxn_time float64 0 2.16k ⌀ | procedure_details stringlengths 8 24.5k | product_000 stringlengths 1 484 | product_001 null | yield_000 float64 0 90,205,156,600B ⌀ | yield_001 float64 0 100M ⌀ |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1,754,318 | ord_dataset-97eb2ab57fec4160922caae33b54d956 | null | 2016-01-01T00:08:00 | true | [OH:1][C:2]1[CH:6]=[C:5]([CH2:7][CH2:8][C:9]([OH:11])=O)[O:4][N:3]=1.CCN(C(C)C)C(C)C.[C:21]([N:28]1[CH2:33][CH2:32][CH:31]([CH2:34][NH2:35])[CH2:30][CH2:29]1)([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22]>CN(C=O)C>[OH:1][C:2]1[CH:6]=[C:5]([CH2:7][CH2:8][C:9]([NH:35][CH2:34][CH:31]2[CH2:32][CH2:33][N:28]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:29][CH2:30]2)=[O:11])[O:4][N:3]=1 | CC(C)(C)OC(=O)N1CCC(CN)CC1 | O=C(O)CCc1cc(O)no1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(C(C)C)C(C)C | CN(C)C=O | null | null | null | null | null | null | null | null | null | 25 | 0.08 | To 3-(3-hydroxyisoxazol-5-yl)propanoic acid (300 mg, 1.909 mmol) in DMF (7 mL) was added DIPEA (0.667 mL, 3.82 mmol) followed by 1-[(1-(cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylaminomorpholino)]uronium hexafluorophosphate (COMU) (981 mg, 2.291 mmol). The resulting brown solution was stirred at RT for 5 mins and then treated with 1-BOC-4-(aminomethyl)piperidine (409 mg, 1.909 mmol). After stirring at RT for 2 hrs, the solution was concentrated under reduced pressure and the residue suspended in 0.2M aqueous HCl (200 ml). The mixture was extracted with EtOAc (2×100 ml) and the combined extracts were dried (MgSO4) and concentrated under reduced pressure. The crude residue was dissolved in DCM (100 ml) and treated with 2M NaOH (50 ml). The mixture was stirred vigorously at ambient temperature for 16 hrs. The mixture was then acidified with citric acid and the organics removed, dried (MgSO4) and concentrated under reduced pressure. The residue was applied to a 24 g silica cartridge and eluted with 0-100% EtOAc/iso-hexane. The product fractions were combined and concentrated to give a tert-butyl 4-((3-(3-hydroxyisoxazol-5-yl)propanamido)methyl)piperidine-1-carboxylate as a gum. | CC(C)(C)OC(=O)N1CCC(CNC(=O)CCc2cc(O)no2)CC1 | null | null | null |
1,751,943 | ord_dataset-97eb2ab57fec4160922caae33b54d956 | null | 2016-01-01T00:08:00 | true | [CH:1]1([CH2:4][N:5]2[CH:9]=[C:8]([N+:10]([O-])=O)[CH:7]=[N:6]2)[CH2:3][CH2:2]1>CO.[Pd]>[CH:1]1([CH2:4][N:5]2[CH:9]=[C:8]([NH2:10])[CH:7]=[N:6]2)[CH2:3][CH2:2]1 | O=[N+]([O-])c1cnn(CC2CC2)c1 | null | null | [Pd] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | 25 | 2 | To a solution of 1-(cyclopropylmethyl)-4-nitro-1H-pyrazole (8.37 g, 50.1 mmol) in methanol (150 mL) was added 10% Pd/C (840.0 mg, 0.7893 mmol). The suspension was stirred at room temperature under a H2 atmosphere for 2 h. Filtered and the filter cake was washed with MeOH (50 mL×3). The filtrate was concentrated in vacuo and the residue was purified by silica gel column chromatography (MeOH/DCM (v/v)=1/100 to 1/50) to give the title compound as purple oil (5.5 g, 80%). | Nc1cnn(CC2CC2)c1 | null | 80 | null |
382,178 | ord_dataset-f367d8d2baac490b9204609a79420961 | null | 1997-01-01T00:11:00 | true | [OH-].[Na+].[CH3:3][O:4][C:5]1[CH:30]=[CH:29][C:8]([CH2:9][N:10]2[C:14]([C:15]([O-:17])=[O:16])=[C:13]([C:18](=[O:28])[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[N+:25]([O-:27])=[O:26])[N:12]=[N:11]2)=[CH:7][CH:6]=1.Cl>O1CCCC1>[CH3:3][O:4][C:5]1[CH:6]=[CH:7][C:8]([CH2:9][N:10]2[C:14]([C:15]([OH:17])=[O:16])=[C:13]([C:18](=[O:28])[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[N+:25]([O-:27])=[O:26])[N:12]=[N:11]2)=[CH:29][CH:30]=1 | COc1ccc(Cn2nnc(C(=O)c3ccccc3[N+](=O)[O-])c2C(=O)[O-])cc1 | null | null | Cl | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | 25 | 2 | A 1N aqueous sodium hydroxide solution (50 ml) was added to a solution of 1-(4-methoxybenzyl)-4-(2-nitrobenzoyl)-1,2,3-triazole-5-carboxylate (b-1) (10.17 g, 24.8 mmole) in tetrahydrofuran (100 ml), which was stirred at room temperature for 2 hours. The aqueous layer was acidified with hydrochloric acid, extracted with ethyl acetate and washed with saturated aqueous saline. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure to give 1-(4-methoxybenzyl)-4-(2-nitrobenzoyl)-1,2,3-triazole-5-carboxylic acid (c-1': LP) as a colorless crystalline powder. The product was dissolved in methanol (80 ml), 10% palladium on carbon (800 mg) was added, and the mixture was stirred in the hydrogen atmosphere at room temperature for 10 hours. The reaction mixture was filtered through celite, and the filtrate was concentrated under reduced pressure. Precipitates were collected by filtration to give 4-(2-aminobenzoyl)-1-(4-methoxybenzyl)-1,2,3-triazole-5-carboxylic acid (c-1: LP) (6.62 g, 75.8% over two steps) as a yellow crystalline powder. | COc1ccc(Cn2nnc(C(=O)c3ccccc3[N+](=O)[O-])c2C(=O)O)cc1 | null | null | null |
1,041,676 | ord_dataset-3af92aec23dc4810b92eb0d8c60023ee | null | 2011-01-01T00:03:00 | true | [C:1]([O:5][C:6](=[O:32])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([S:14][C:15]2[CH:20]=[CH:19][C:18]([C:21](=[O:30])[NH:22][C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([Br:29])[CH:24]=3)=[CH:17][C:16]=2[NH2:31])=[CH:10][CH:9]=1)([CH3:4])([CH3:3])[CH3:2].C([C:35]1[C:36]([N:42]=[CH:43][N:44]([CH3:46])C)=[N:37][C:38]([CH3:41])=[CH:39][CH:40]=1)#N>>[C:1]([O:5][C:6](=[O:32])[NH:7][C:8]1[CH:9]=[CH:10][C:11]([S:14][C:15]2[CH:20]=[CH:19][C:18]([C:21](=[O:30])[NH:22][C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([Br:29])[CH:24]=3)=[CH:17][C:16]=2[NH:31][C:46]2[C:35]3[CH:40]=[CH:39][C:38]([CH3:41])=[N:37][C:36]=3[N:42]=[CH:43][N:44]=2)=[CH:12][CH:13]=1)([CH3:4])([CH3:2])[CH3:3] | CC(C)(C)OC(=O)Nc1ccc(Sc2ccc(C(=O)Nc3cccc(Br)c3)cc2N)cc1 | Cc1ccc(C#N)c(N=CN(C)C)n1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The product of Example 64A was reacted with the product of Example 9B using the procedure of Example 13D substituting the product of Example 64A for the product of Example 13C and substituting the product of Example 9B for the product of Example 8E to provide the crude title compound which was purified by column chromatography on silica gel using methanol/dichloromethane as eluent to provide the title compound (27 mg, 21%). 1H NMR (300 MHz, DMSO-D6) δ ppm: 1.48 (s, 9 H) 2.69 (s, 3 H) 7.00 (d, J=8.09 Hz, 1 H) 7.34 (m, 4 H) 7.54 (m, 3 H) 7.72 (m, 1 H) 7.81 (d, J=8.09 Hz, 1 H) 8.01 (s, 1 H) 8.07 (s, 1 H) 8.60 (s, 1 H) 8.82 (d, J=8.46 Hz, 1 H) 9.60 (s, 1 H) 10.22 (s, 1 H) 10.34 (s, 1 H); MS (ESI+) m/z 657, 659 (M+H)+. | Cc1ccc2c(Nc3cc(C(=O)Nc4cccc(Br)c4)ccc3Sc3ccc(NC(=O)OC(C)(C)C)cc3)ncnc2n1 | null | 21 | null |
117,849 | ord_dataset-3708161f4ba04e959b9a7a8d59fd86e1 | null | 1984-01-01T00:05:00 | true | [CH2:1]([O:8][C:9]1[CH:18]=[CH:17][C:16]2[CH2:15][CH:14]([N:19]=[N+]=[N-])[CH2:13][CH2:12][C:11]=2[C:10]=1[C:22]([NH2:24])=[O:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(C)C.[BH4-].[Na+].Cl>O>[CH2:1]([O:8][C:9]1[CH:18]=[CH:17][C:16]2[CH2:15][CH:14]([NH2:19])[CH2:13][CH2:12][C:11]=2[C:10]=1[C:22]([NH2:24])=[O:23])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1 | [N-]=[N+]=NC1CCc2c(ccc(OCc3ccccc3)c2C(N)=O)C1 | null | null | Cl | [BH4-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(C)O | O | null | null | null | null | null | null | null | null | null | null | null | A solution was prepared from 3.4 g. of dl-2-benzyloxy-6-azido-5,6,7,8-tetrahydro-1-naphthalenecarboxamide (from Example 4) and 100 ml. of isopropanol. The solution was cooled and 0.5 g. sodium borohydride added thereto in small portions. After the addition had been completed, the reaction mixture was heated to reflux temperature under a nitrogen blanket for about 18 hours. The reaction mixture was then cooled and the cooled mixture diluted with water. The aqueous mixture was made acidic by the addition of 1 N aqueous hydrochloric acid. The aqueous acidic layer was extracted with ether and the ether extract discarded. The aqueous acidic layer was made basic by the addition of 10% aqueous sodium hydroxide. The alkaline layer was extracted several times with equal volumes of a 3:1 chloroform/methanol solvent mixture. The organic extracts were combined and the combined extracts washed with saturated aqueous sodium chloride and then dried. Evaporation of the solvent therefrom yielded a residue comprising dl-2-benzyloxy-6-amino-5,6,7,8-tetrahydro-1-naphthalenecarboxamide. TLC indicated a single spot at the origin. An infrared spectrum of the solid indicated no absorption attributable to an azide group. The residue was dissolved in chloroform and the chloroform solution saturated with gaseous hydrogen chloride. The solvent was removed in vacuo and the residue dissolved in methanol. Ether was added to the point of incipient precipitation and the solution was cooled overnight. Forty-eight hundredths grams of tan crystals melting above 235° C. consisting of dl-2-benzyloxy-6-amino-5,6,7,8-tetrahydro-1-naphthalenecarboxamide hydrochloride were recovered. | NC(=O)c1c(OCc2ccccc2)ccc2c1CCC(N)C2 | null | null | null |
1,745,103 | ord_dataset-60a3e71da3174666a50a61dcfa611a9f | null | 2016-01-01T00:07:00 | true | Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[Cl:12])[CH:5]=[C:4]([C@@H:13]([NH:15][C:16]2[N:24]=[CH:23][N:22]=[C:21]3[C:17]=2[N:18]=[CH:19][N:20]3[CH2:25][C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=2)[CH3:14])[N:3]=1.O.[CH3:35][N:36](C=O)C>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:12][C:10]1[CH:9]=[CH:8][CH:7]=[C:6]2[C:11]=1[C:2]([C:35]#[N:36])=[N:3][C:4]([C@@H:13]([NH:15][C:16]1[N:24]=[CH:23][N:22]=[C:21]3[C:17]=1[N:18]=[CH:19][N:20]3[CH2:25][C:26]1[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=1)[CH3:14])=[CH:5]2 | CN(C)C=O | COc1ccc(Cn2cnc3c(N[C@@H](C)c4cc5cccc(Cl)c5c(Cl)n4)ncnc32)cc1 | null | c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | null | null | null | null | null | null | null | null | null | null | 100 | 8 | To a stirred solution of ((S)—N-(1-(1,8-dichloroisoquinolin-3-yl)ethyl)-9-(4-methoxybenzyl)-9H-purin-6-amine 1 (1.5 g, 3.1 mmol, 1.0 eq) and tetrakis(triphenylphosphine)palladium (181 mg, 0.16 mmol, 0.05 eq) in DMF (50 mL) at RT, dicyanozine (476 mg, 4.06 mmol, 1.3 eq) was added and the resulting mixture was stirred at 100° C. overnight. The reaction mixture was poured into water (100 mL) and extracted with DCM (3×100 mL). The combined organic layers were washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by flash column chromatography on silica gel (1-10% MeOH-DCM) to afford the product (S)-8-chloro-3-(1-((9-(4-methoxybenzyl)-9H-purin-6-yl)amino)ethyl)isoquinoline-1-carbonitrile 29. | COc1ccc(Cn2cnc3c(N[C@@H](C)c4cc5cccc(Cl)c5c(C#N)n4)ncnc32)cc1 | null | null | null |
852,804 | ord_dataset-faa0236be76c4501841c954527cd1b6c | null | 2008-01-01T00:12:00 | true | [C:1]([C:3]1[CH:15]=[CH:14][C:6]2[O:7][CH2:8][C:9]([CH3:13])([CH3:12])[CH2:10][O:11][C:5]=2[CH:4]=1)#[CH:2].I[C:17]1[CH:22]=[CH:21][C:20]([C:23](=[O:25])[CH3:24])=[CH:19][CH:18]=1>>[CH3:13][C:9]1([CH3:12])[CH2:8][O:7][C:6]2[CH:14]=[CH:15][C:3]([C:1]#[C:2][C:17]3[CH:22]=[CH:21][C:20]([C:23](=[O:25])[CH3:24])=[CH:19][CH:18]=3)=[CH:4][C:5]=2[O:11][CH2:10]1 | CC(=O)c1ccc(I)cc1 | C#Cc1ccc2c(c1)OCC(C)(C)CO2 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The title compound is prepared in analogy to example 1 from 7-ethynyl-3,3-dimethyl-3,4-dihydro-2H-benzo[b][1,4]dioxepine (6) (example 1d) and 1-(4-iodo-phenyl)-ethanone. MS (ESI) 320.2 (M•)+. | CC(=O)c1ccc(C#Cc2ccc3c(c2)OCC(C)(C)CO3)cc1 | null | null | null |
1,155,534 | ord_dataset-b195433d5c354ddfb6cde0d53c41910f | null | 2012-01-01T00:04:00 | true | [C:1]([CH:3]1[C:12]2[CH2:11][CH2:10][C:9]3=[N:13][N:14]([CH2:16][C:17]4[C:22]([CH3:23])=[C:21]([O:24][CH3:25])[C:20]([CH3:26])=[CH:19][N:18]=4)[N:15]=[C:7]([C:8]=23)[C:6]([N:27](C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)=[N:5][S:4]1)#[N:2].Cl.C(N(CC)CC)C.[N-:50]=[N+:51]=[N-:52].[Na+]>CN(C)C=O>[CH3:25][O:24][C:21]1[C:20]([CH3:26])=[CH:19][N:18]=[C:17]([CH2:16][N:14]2[N:13]=[C:9]3[CH2:10][CH2:11][C:12]4[CH:3]([C:1]5[NH:2][N:52]=[N:51][N:50]=5)[S:4][N:5]=[C:6]([NH2:27])[C:7]([C:8]=43)=[N:15]2)[C:22]=1[CH3:23] | COc1c(C)cnc(CN2N=C3CCC4=C3C(=N2)C(N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)=NSC4C#N)c1C | [N-]=[N+]=[N-] | null | Cl | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | CCN(CC)CC | null | null | null | null | null | null | null | null | null | 105 | 15 | A mixture composed of di-tert-butyl {7-cyano-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-2,7,8,9-tetrahydro-6-thia-1,2,3,5-tetraazabenzo[cd]azulen-4-yl}imidodicarbonate of Step 4) of Example 23 (53 mg), N,N-dimethylformamide (1 mL), triethylamine hydrochloride (14.5 m) and sodium azide (6.8 mg) was sealed in a tube and heated with stirring at a bath temperature of 105° C. for 15 hours. After cooling to room temperature, the reaction solution was separated with ethyl acetate and a 0.1 N sodium hydroxide solution. The aqueous layer was made acidic with a 0.1 N hydrochloric acid solution, followed by extraction with ethyl acetate. The organic layer was washed with water and then dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. Dichloromethane (2 mL) and trifluoroacetic acid (0.5 mL) were added to the resulting residue, and the mixture was stirred at room temperature for two hours. The reaction solution was concentrated under reduced pressure, and the resulting residue was purified by silica gel thin-layer chromatography (chloroform-methanol-lower layer of water) to obtain the title compound (5.6 mg, 19%) as a solid. | COc1c(C)cnc(CN2N=C3CCC4=C3C(=N2)C(N)=NSC4c2nnn[nH]2)c1C | null | 19 | null |
428,592 | ord_dataset-8cce6f317d644b348a7978a2dce3ea01 | null | 1999-01-01T00:03:00 | true | I[CH2:2][C:3]([O:5][CH:6]([C:9]1[CH:25]=[C:24]2[N:12]([CH2:13][C:14]3[C:15]2=[N:16][C:17]2[C:22]([CH:23]=3)=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:11](=[O:26])[C:10]=1[CH3:27])[CH2:7][CH3:8])=[O:4].[NH:28]1[CH:32]=[CH:31][N:30]=[CH:29]1.[ClH:33]>O>[ClH:33].[N:28]1([CH2:2][C:3]([O:5][CH:6]([C:9]2[CH:25]=[C:24]3[N:12]([CH2:13][C:14]4[C:15]3=[N:16][C:17]3[C:22]([CH:23]=4)=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:11](=[O:26])[C:10]=2[CH3:27])[CH2:7][CH3:8])=[O:4])[CH:32]=[CH:31][N:30]=[CH:29]1 | CCC(OC(=O)CI)c1cc2n(c(=O)c1C)Cc1cc3ccccc3nc1-2 | c1c[nH]cn1 | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | null | null | null | null | null | null | null | null | null | null | null | null | The title compound was prepared according to the procedure in Example 13 except using (±)-7-[1-[(iodoacetyl)oxy]propyl]-8-methylindolizino[1,2-b]quinolin-9(11H)-one and imidazole. 1H NMR (CDCl3 /MeOH-d4) d 9.17 (s, 1H), 8.60 (s, 1H), 8.34 (d, 1H), 8.04 (d, 1H), 7.95 (m, 1H), 7.75 (m, 1H), 7.61 (s, 1H), 7.51 (br s, 1H), 7.41 (br s, 1H), 5.95 (m, 1H), 5.65 (d, 1H), 5.42 (d, 1H), 5.33 (s, 2H), 2.36 (s, 3H), 2.1-1.9 (m, 2H), 1.07 (t, 3H). Anal. Calcd for C24H22N4O3.2 HCl.11/4 H2O: C, 53.68; H, 5.35; N, 10.43. Found: C, 53.52; H, 5.58; N, 10.29. | CCC(OC(=O)Cn1ccnc1)c1cc2n(c(=O)c1C)Cc1cc3ccccc3nc1-2 | null | null | null |
1,671,505 | ord_dataset-9cc455db05a444779921f786a45b21a6 | null | 2015-01-01T00:12:00 | true | [C:1]([O:5][C:6]([NH:8][CH:9]1[CH2:14][CH2:13][CH:12]([O:15][C:16]2[C:17]3[C:18]4[C@H:19]([CH2:29][C:30](OCC)=[O:31])[CH2:20][CH2:21][CH2:22][C:23]=4[S:24][C:25]=3[N:26]=[CH:27][N:28]=2)[CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[OH:31][CH2:30][CH2:29][C@H:19]1[C:18]2[C:17]3[C:16]([O:15][CH:12]4[CH2:13][CH2:14][CH:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:2])[CH3:4])[CH2:10][CH2:11]4)=[N:28][CH:27]=[N:26][C:25]=3[S:24][C:23]=2[CH2:22][CH2:21][CH2:20]1 | CCOC(=O)C[C@@H]1CCCc2sc3ncnc(OC4CCC(NC(=O)OC(C)(C)C)CC4)c3c21 | null | null | [Al+3] | [H-] | [Li+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | 25 | 2 | To a solution of ethyl 2-[(13S)-3-[(4-[[(tert-butoxy)carbonyl]amino]cyclohexyl)oxy]-8-thia-4,6-diazatricyclo[7.4.0.0[2,7]]trideca-1(9),2(7),3,5-tetraen-13-yl]acetate (800 mg, 1.63 mmol, 1.00 equiv) in THF (30 mL) in an ice/water bath under nitrogen was added LiAlH4 (121.2 mg, 3.20 mmol, 2.00 equiv). The resulting solution was stirred for 2 h at room temperature and quenched with water, extracted with ethyl acetate (80 mL), dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:1) to give 490 mg (67%) of tert-butyl N-(4-[[(13S)-13-(2-hydroxyethyl)-8-thia-4,6-diazatricyclo[7.4.0.0[2,7]]trideca-1(9),2(7),3,5-tetraen-3-yl]oxy]cyclohexyl)carbamate as a colorless oil. | CC(C)(C)OC(=O)NC1CCC(Oc2ncnc3sc4c(c23)[C@H](CCO)CCC4)CC1 | null | 67.2 | null |
295,903 | ord_dataset-ec7cb3d5a8704f64b01d401ea555974f | null | 1994-01-01T00:09:00 | true | C[O:2][C:3](=[O:23])[C:4](=[O:22])[C:5]1[CH:10]=[CH:9][C:8]([O:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)=[CH:7][CH:6]=1.[OH-].[Na+]>CO.O>[O:22]=[C:4]([C:5]1[CH:6]=[CH:7][C:8]([O:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)=[CH:9][CH:10]=1)[C:3]([OH:23])=[O:2] | COC(=O)C(=O)c1ccc(OCCCCc2cccnc2)cc1 | null | null | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CO | null | null | null | null | null | null | null | null | null | null | null | A mixture of alpha-oxo-4-[4-(3-pyridinyl)butoxy]benzeneacetic acid methyl ester (4:1) molar hydrate (1.1 g) in hot methanol (10 mL) was treated with 1N sodium hydroxide (5 mL) and diluted with water. The organic solvent was removed under vacuum and the residue in water was washed with diethyl ether. The aqueous layer was concentrated to about 25 mL and chilled in ice. Cold 2N hydrochloric acid (2.5 mL) was added dropwise and the product was allowed to crystallize and was filtered and air dried. Recrystallization from acetone provided 0.64 g of alpha-oxo-4-[4-(3-pyridinyl)butoxy]benzeneacetic acid as a colorless solid, mp 163°-165° C. | O=C(O)C(=O)c1ccc(OCCCCc2cccnc2)cc1 | null | null | null |
1,480,759 | ord_dataset-c3c1091f873b4f40827973a6f1f9b685 | null | 2014-01-01T00:09:00 | true | [C:1]1(=O)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]2([CH2:12][CH2:11]2)[C:3](=O)[NH:2]1.B.CO>C1COCC1>[CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]2([CH2:12][CH2:11]2)[CH2:3][NH:2]1 | O=C1NC(=O)C2(CC2)c2ccccc21 | null | null | B | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | CO | null | null | null | null | null | null | null | null | null | 0 | null | 0.5 g (2.7 mmol) 1′H-spiro[cyclopropane-1,4′-isoquinoline]-1′,3′(2′H)-dione in 50 mL THF were heated to the reflux temperature of the solvent. 11 mL (11 mmol) of a 1M borane in THF solution were added dropwise and the mixture was refluxed for 3 h. The reaction mixture was cooled to 0° C. and mixed with 50 mL methanol. The reaction mixture was evaporated down, the residue was combined with 15 mL of a 4M hydrochloric acid solution and refluxed for 30 min. After neutralisation with 15 mL of an aqueous 4M sodium hydroxide solution the mixture was extracted twice with ethyl acetate. The combined organic phases were dried and evaporated down. The product was purified by HPLC. The product-containing fractions were combined and evaporated down. | c1ccc2c(c1)CNCC21CC1 | null | null | null |
127,767 | ord_dataset-e61c1950b2fc468dbf0701c65768f73f | null | 1985-01-01T00:03:00 | true | [C:1]1([S:7][C:8]2[CH2:14][CH:13]3[CH:10]([C:11](=[O:18])[CH:12]3[CH:15]([OH:17])[CH3:16])[C:9]=2[C:19]([O:21][CH:22]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:20])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.ClC1C=CC=C(C(OO)=[O:43])C=1>C(Cl)Cl>[C:1]1([S:7]([C:8]2[CH2:14][CH:13]3[CH:10]([C:11](=[O:18])[CH:12]3[CH:15]([OH:17])[CH3:16])[C:9]=2[C:19]([O:21][CH:22]([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:20])=[O:43])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1 | O=C(OO)c1cccc(Cl)c1 | CC(O)C1C(=O)C2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(Sc3ccccc3)CC21 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | 25 | 0.75 | To a solution of 200 mg of 3-phenylthio-6-(1-hydroxyethyl)-7-oxobicyclo[3.2.0]hept-2-en-2-carboxylic acid, diphenylmethyl ester, in 15 mL of methylene chloride at -50° under nitrogen was added 90 mg of m-chloroperbenzoic acid in 3 mL of methylene chloride. The solution was stirred at -40° for 45 min and then warmed to room temperature over a 45 min period. The mixture was partitioned between methylene chloride and aqueous sodium sulfite. The organic layer was washed twice with bicarbonate, then brine, then dried over sodium sulfate and evaporated to dryness. The crude reaction product was purified by preparative thin layer chromatography two 20×20×0.2 cm silica gel plates, eluting with 5% methanol in methylene chloride, to afford 144 mg (69.6%) of 3-phenylsulfinyl-6-(1-hydroxyethyl)-7-oxobicyclo[3.2.0]-hept-2-en-2-carboxylic acid, diphenylmethyl ester, a diastereomeric mixture, as a colorless glass. IR (Nujol mull): 1780, 1710, 1600, 3400 cm-1 ; NMR (220 MHz; CDCl3 indicative of a 3:1 mixture of diastereoisomers at sulfur): δ 1.15 (3H, d, J=6.5, major isomer), 1.30 (3H, d, J=6.5, minor isomer), 2.3-3.0 (3H, m), 3.3-3.6(1H, m), 3.93 (1H, m, major isomer), 4.02 (1H, m, minor isomer), 4.52 (1H, m, minor isomer), 4.68 (1H, m, major isomer), 6.95 (1H, s), and 7.2-7.7 (15H, m). ##STR25## | CC(O)C1C(=O)C2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(S(=O)c3ccccc3)CC21 | null | 69.6 | null |
900,148 | ord_dataset-de6bce51790e4004a27e1a8f2bcc7ded | null | 2009-01-01T00:08:00 | true | [NH2:1][C:2]1[CH:10]=[CH:9][C:5]([CH2:6][C:7]#[N:8])=[CH:4][CH:3]=1>O>[CH3:5][C:4]1[N:1]([C:2]2[CH:10]=[CH:9][C:5]([CH2:6][C:7]#[N:8])=[CH:4][CH:3]=2)[C:10]([CH3:9])=[CH:2][CH:3]=1 | N#CCc1ccc(N)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | null | null | null | null | null | null | null | null | null | null | null | null | 20 g (0.15 mol) of p-aminobenzyl cyanide, 19 ml (0.17 mol) of 2,5-dicetohexane and 2.88 g (0.015 mol) of hydrated p-toluene sulphonic acid are dissolved in a 500 ml flask. This mixture is heated to reflux, the water formed is trapped using a Dean Stark apparatus. At the end of the reaction, the solvent is evaporated off under vacuum and the residue is taken up in 300 ml of AcOEt. The organic solution is washed successively with twice 200 ml of water, 200 ml of a saturated solution of Na2CO3, 200 ml of water, 200 ml of a saturated solution of KHSO4 and finally 200 ml of water and 200 ml of brine. After drying over sodium sulphate, filtration and concentration under vacuum, the residue is purified rapidly on a silica column. A light beige solid is obtained with a yield of 34%. Melting point: 112-113° C. | Cc1ccc(C)n1-c1ccc(CC#N)cc1 | null | 34 | null |
237,027 | ord_dataset-56e7a343b17a4d6da818127ceb19589d | null | 1991-01-01T00:11:00 | true | ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl.[CH:15]([C:18]1[NH:19][C:20]([CH:41]([CH3:43])[CH3:42])=[C:21]([C:36]([O:38][CH2:39][CH3:40])=[O:37])[CH:22]([C:29]2[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=2)[C:23]=1[C:24]([O:26][CH2:27][CH3:28])=[O:25])([CH3:17])[CH3:16]>C(Cl)Cl>[CH:41]([C:20]1[C:21]([C:36]([O:38][CH2:39][CH3:40])=[O:37])=[C:22]([C:29]2[CH:30]=[CH:31][C:32]([F:35])=[CH:33][CH:34]=2)[C:23]([C:24]([O:26][CH2:27][CH3:28])=[O:25])=[C:18]([CH:15]([CH3:17])[CH3:16])[N:19]=1)([CH3:43])[CH3:42] | CCOC(=O)C1=C(C(C)C)NC(C(C)C)=C(C(=O)OCC)C1c1ccc(F)cc1 | null | null | N#CC1=C(C#N)C(=O)C(Cl)=C(Cl)C1=O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | 25 | 1 | 3.8 g (16.4 mmol) of 2,3-dichloro-5,6-dicyano-p-benzoquinone are added to a solution of 6.6 g (16.4 mmol) of the compound from Example II in 200 ml of methylene chloride p.A. and the mixture is stirred at room temperature for 1 hour. It is then filtered through kieselguhr with suction, and the methylene chloride phase is extracted 3 times with 100 ml of water each time and dried over magnesium sulphate. After concentrating in vacuo, the residue is chromatographed on a column (100 g of silica gel 70-230 mesh, φ 3.5 cm, using ethyl acetate/ petroleum ether 1:9) | CCOC(=O)c1c(C(C)C)nc(C(C)C)c(C(=O)OCC)c1-c1ccc(F)cc1 | null | null | null |
576,343 | ord_dataset-f4512fe8cd804ac79da66cbc0c2b9d42 | null | 2002-01-01T00:12:00 | true | C1(CN2CCC(C[CH2:15][C:16]3[C:20]4[CH:21]=[CH:22][C:23]5[NH:27][C:26](=[O:28])[CH2:25][C:24]=5[C:19]=4[O:18][N:17]=3)CC2)C=CC=CC=1.N1C=CC=CC=1>CN(C=O)C>[CH3:15][C:16]1[C:20]2[CH:21]=[CH:22][C:23]3[NH:27][C:26](=[O:28])[CH2:25][C:24]=3[C:19]=2[O:18][N:17]=1 | O=C1Cc2c(ccc3c(CCC4CCN(Cc5ccccc5)CC4)noc23)N1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | c1ccncc1 | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | null | The procedure described in Example 33d was followed with the oxime acetate obtained in step c (0.334 g, 1.35 mmol) and pyridine (0.55 mL, 6.75 mmol) in DMF (25 mL). After work-up, the residue was purified by silica gel flash chromatography (50→75% EtOAc-hexanes) to give the title compound (0.086 g, 34%) as a white solid. | Cc1noc2c3c(ccc12)NC(=O)C3 | null | 33.9 | null |
1,515,890 | ord_dataset-8c74302143c04eb9983e4b3a7ead2d72 | null | 2014-01-01T00:12:00 | true | Br[C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:18]([F:21])([CH3:20])[CH3:19])=[N:7][N:8]2[C:11]2[CH:16]=[CH:15][N:14]=[C:13]([NH2:17])[N:12]=2)=[CH:4][CH:3]=1.[CH3:22][C:23]1[O:27][N:26]=[C:25]([C@:28]([OH:32])([C:30]#[CH:31])[CH3:29])[N:24]=1>N1CCCCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[NH2:17][C:13]1[N:12]=[C:11]([N:8]2[C:9]3[C:5](=[CH:4][CH:3]=[C:2]([C:31]#[C:30][C@:28]([C:25]4[N:24]=[C:23]([CH3:22])[O:27][N:26]=4)([OH:32])[CH3:29])[CH:10]=3)[C:6]([C:18]([F:21])([CH3:20])[CH3:19])=[N:7]2)[CH:16]=[CH:15][N:14]=1 | C#C[C@@](C)(O)c1noc(C)n1 | CC(C)(F)c1nn(-c2ccnc(N)n2)c2cc(Br)ccc12 | null | [Cu]I | c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCNCC1 | null | null | null | null | null | null | null | null | null | null | 66 | null | To a solution of 4-[6-bromo-3-(2-fluoropropan-2-yl)-1H-indazol-1-yl]pyrimidin-2-amine (95 mg, 0.26 mmol) in piperidine (1 mL) was introduced tetrakis(triphenylphosphine)palladium (0) (24 mg, 0.02 mmol), copper(I) iodide (4 mg, 0.02 mmol) and (2R)-2-(5-methyl-1,2,4-oxadiazol-3-yl)but-3-yn-2-ol (79 mg, 0.52 mmol). The reaction mixture was warmed to 66° C. for 2 hr. After cooling to RT, the reaction mixture was concentrated in vacuo and the residue purified by flash chromatography (Biotage, eluent:DCM containing a 1-10% MeOH gradient). Further purification by reverse phase preparative HPLC furnished the title compound as an orange solid: 1H NMR (500 MHz, DMSO) delta 1.76-2.00 (9H, m), 2.62 (3H, s), 6.82 (1H, s), 6.95-7.15 (3H, m), 7.39 (1H, d, J=9.93 Hz), 7.95 (1H, d, J=9.93 Hz), 8.33 (1H, br. s.), 8.94 (1H, s); LC-MS: m/z=+422.05 (M+H)+. | Cc1nc([C@](C)(O)C#Cc2ccc3c(C(C)(C)F)nn(-c4ccnc(N)n4)c3c2)no1 | null | null | null |
1,001,517 | ord_dataset-70899a0178cc441482746c093624afa0 | null | 2010-01-01T00:10:00 | true | [H-].[Na+].C1COCC1.[N:8]1([CH2:14][CH2:15][CH2:16][OH:17])[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1.[CH2:18]([C:20]1[N:21]=[N+:22]([O-:31])[C:23]2[CH:29]=[CH:28][C:27](F)=[CH:26][C:24]=2[N:25]=1)[CH3:19]>O>[CH2:18]([C:20]1[N:21]=[N+:22]([O-:31])[C:23]2[CH:29]=[CH:28][C:27]([O:17][CH2:16][CH2:15][CH2:14][N:8]3[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)=[CH:26][C:24]=2[N:25]=1)[CH3:19] | CCc1nc2cc(F)ccc2[n+]([O-])n1 | OCCCN1CCOCC1 | null | [H-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | C1CCOC1 | null | null | null | null | null | null | null | null | null | 20 | 0.33 | NaH (60% dispersion in oil, 310 mg, 7.75 mmol) was added to dry THF (10 mL) and stirred at 20° C. for 20 min prior to the addition of 3-(4-morpholinyl)propanol (676 mg, 4.66 mmol). The mixture was stirred for 30 min, fluoride 28 (300 mg, 1.55 mmol) added and the resulting solution stirred at 20° C. for 2.5 h under N2. Water was added and the solution extracted with DCM (4×30 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by column chromatography, eluting with a gradient (0-5%) MeOH/DCM to give 1-oxide 31 (257 mg, 52%) as a pale yellow solid, mp 108-111° C.; 1H NMR δ 8.33 (d, J=9.3 Hz, 1 H, H-8), 7.21-7.26 (m, 2 H, H-7 and H-5), 4.22 (t, J=6.4 Hz, 2 H, CH2), 3.73 (t, J=4.6 Hz, 4 H, 2×CH2O), 3.00 (q, J=7.6 Hz, 2 H, CH2), 2.55 (t, J=7.0 Hz, 2 H, CH2), 2.48 (t, J=4.6 Hz, 4 H, 2×CH2N), 2.06 (m, 2 H, CH2), 1.43 (t, J=7.6 Hz, 3 H, CH3); 13C NMR δ 168.7, 164.6, 150.3, 128.4, 123.1, 121.6, 106.3, 67.3 (2), 66.9, 55.1, 53.7 (2), 30.7, 26.0, 12.2. Anal. Calcd for C16H22N4O3: C, 60.4; H, 7.0; N, 17.6. Found: C, 60.4; H, 7.0; N, 17.4%. | CCc1nc2cc(OCCCN3CCOCC3)ccc2[n+]([O-])n1 | null | 52.1 | null |
645,841 | ord_dataset-c975a50a7600448fabd558f4a94a3e29 | null | 2004-01-01T00:08:00 | true | [CH3:1][C:2]1[CH:13]=[C:12]2[C:5]([NH:6][CH:7]=[C:8]2[CH2:9][CH2:10][NH2:11])=[CH:4][CH:3]=1.C(=O)(O)[O-].[Na+].[N+:19]([C:22]1[CH:27]=[C:26]([N+:28]([O-:30])=[O:29])[CH:25]=[CH:24][C:23]=1F)([O-:21])=[O:20]>O.C(O)C>[N+:19]([C:22]1[CH:27]=[C:26]([N+:28]([O-:30])=[O:29])[CH:25]=[CH:24][C:23]=1[NH:11][CH2:10][CH2:9][C:8]1[C:12]2[C:5](=[CH:4][CH:3]=[C:2]([CH3:1])[CH:13]=2)[NH:6][CH:7]=1)([O-:21])=[O:20] | Cc1ccc2[nH]cc(CCN)c2c1 | O=[N+]([O-])c1ccc(F)c([N+](=O)[O-])c1 | null | O=C([O-])O | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CCO | null | null | null | null | null | null | null | null | null | 25 | 2 | 1 mMole of 5-metyltryptamine was dissolved in 100 ml of water and the pH was adjusted to pH 8.3 with 2.5 moles of sodium bicarbonate (NaHCO3), A 1.5% solution of 2,4-dinitrofluorobenzene in 200 ml ethanol was added and the mixture was stirred during 2 hours at room temperature. The desired product precipitates out, it is washed and dried. The product is obtained in 85% yield, and TLC (chloroform, silica-gel plates, reveals one yellow spot (Rf=0.8) which is well resolved from the starting materials under the same conditions. | Cc1ccc2[nH]cc(CCNc3ccc([N+](=O)[O-])cc3[N+](=O)[O-])c2c1 | null | 85 | null |
285,405 | ord_dataset-d63ab258f4634f87bdebbaff0a341c28 | null | 1994-01-01T00:02:00 | true | [C:1]1([C:7]2[NH:8][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:10]1([C:16](=[O:22])[CH2:17][C:18](=O)[CH2:19][CH3:20])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>C(O)C>[CH2:19]([C:18]1[NH:8][CH:9]=[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[C:17]=1[C:16](=[O:22])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[CH3:20] | C1=C(c2ccccc2)N1 | CCC(=O)CC(=O)c1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | null | null | null | null | null | null | null | null | null | null | null | 8 | The preparation is carried out in accordance with the general procedure in Example 1. The reactants are 2-phenylazirine and 1-phenylpentane-1,3-dione. The reaction product is dissolved in 150 ml of hot ethanol and the solution is allowed to stand overnight at room temperature. The precipitated crystals are filtered with suction. | CCc1[nH]cc(-c2ccccc2)c1C(=O)c1ccccc1 | null | null | null |
1,708,018 | ord_dataset-54347fcace774f89850681d6dec8009f | null | 2016-01-01T00:03:00 | true | [Br:1][C:2]1[CH:15]=[CH:14][C:13]2[O:12][C:11]3[C:6](=[CH:7][C:8]([I:16])=[CH:9][CH:10]=3)[C@@:5]3([N:21]=[C:20]([NH:22]C(=O)OC(C)(C)C)[CH2:19][O:18][CH2:17]3)[C:4]=2[CH:3]=1.FC(F)(F)C(O)=O>>[Br:1][C:2]1[CH:15]=[CH:14][C:13]2[O:12][C:11]3[C:6](=[CH:7][C:8]([I:16])=[CH:9][CH:10]=3)[C@@:5]3([N:21]=[C:20]([NH2:22])[CH2:19][O:18][CH2:17]3)[C:4]=2[CH:3]=1 | CC(C)(C)OC(=O)NC1=N[C@@]2(COC1)c1cc(Br)ccc1Oc1ccc(I)cc12 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O=C(O)C(F)(F)F | null | null | null | null | null | null | null | null | null | null | null | 2 | In a 150-mL resealable vessel, the (S)-tert-butyl 2′-bromo-7′-iodo-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthene]-5-ylcarbamate (1.475 g, 2.58 mmol) was dissolved in dcm (10 mL), and 2,2,2-trifluoroacetic acid (1.989 mL, 25.8 mmol) was added. The vessel was sealed and placed in a 50° C. oil bath. After 2 h, the reaction was concentrated and the mixture was neutralized with 0.5 M aqueous Na2CO3 (15 mL) and the aqueous phase was extracted with 5% MeOH-dcm (3×33 mL). The organics were combined, washed with dilute brine (10 mL), dried over sodium sulfate and concentrated. The residue was purified by chromatography (5.5% MeOH/DCM) to afford (S)-2′-bromo-7′-iodo-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (151 mg, 0.321 mmol). MS (m/z) 471/473 (M+H)+. | NC1=N[C@@]2(COC1)c1cc(Br)ccc1Oc1ccc(I)cc12 | null | 12.4 | null |
1,264,726 | ord_dataset-d3580a12b15e46cc91aa73f4f1a4a8cc | null | 2013-01-01T00:03:00 | true | [OH:1][C:2]([C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=1)([CH3:7])[C:3]([O:5]C)=O.F[C:19]1[C:28]([N+:29]([O-])=O)=[CH:27][C:22]([C:23]([O:25][CH3:26])=[O:24])=[C:21]([C:32](F)(F)F)[CH:20]=1>>[CH3:7][C:2]1([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=2)[C:3](=[O:5])[NH:29][C:28]2[CH:27]=[C:22]([C:23]([O:25][CH3:26])=[O:24])[C:21]([CH3:32])=[CH:20][C:19]=2[O:1]1 | COC(=O)C(C)(O)c1cccc(C(F)(F)F)c1 | COC(=O)c1cc([N+](=O)[O-])c(F)cc1C(F)(F)F | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Using methyl 2-hydroxy-2-[3-(trifluoromethyl)phenyl]propanoate and methyl 4-fluoro-5-nitro-2-(trifluoromethyl)benzoate, the title compound was obtained in a similar manner to Reference Example 22 and Reference Example 2. | COC(=O)c1cc2c(cc1C)OC(C)(c1cccc(C(F)(F)F)c1)C(=O)N2 | null | null | null |
1,330,932 | ord_dataset-cfad8b3f00044bcda60a96b019f09872 | null | 2013-01-01T00:08:00 | true | [S:1]([Cl:5])(Cl)(=[O:3])=[O:2].[CH3:6][C@H:7]1[O:12][C@@H:11]([CH3:13])[CH2:10][NH:9][CH2:8]1>CN(C)C1C=CN=CC=1.C(Cl)Cl>[CH3:13][C@H:11]1[O:12][C@@H:7]([CH3:6])[CH2:8][N:9]([S:1]([Cl:5])(=[O:3])=[O:2])[CH2:10]1 | O=S(=O)(Cl)Cl | C[C@@H]1CNC[C@H](C)O1 | null | CN(C)c1ccncc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | 25 | 24 | Sulfuryl dichloride (0.363 ml, 4.47 mmol) was added at room temperature to a solution of cis-2,6-dimethylmorpholine (0.500 ml, 4.06 mmol) and 4-dimethylaminopyridine (496 mg, 4.06 mmol) in CH2Cl2 (5 ml) and the whole was stirred at room temperature for 24 hours. The reaction mixture was quenched with H2O (10 ml) and extracted with ethyl acetate (20 ml×3). The combined organic layer was washed with brine (10 ml), dried over Na2SO4, filtered and concentrated in vacuo to give cis-2,6-dimethylmorpholine-4-sulfonyl chloride. | C[C@@H]1CN(S(=O)(=O)Cl)C[C@H](C)O1 | null | null | null |
413,620 | ord_dataset-275344fd078b4340b89ca0b6e92beb95 | null | 1998-01-01T00:10:00 | true | [C:1]1([CH3:15])[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1OS(C(F)(F)F)(=O)=O.[CH2:16]([NH2:20])[CH2:17][CH2:18][CH3:19]>>[CH2:16]([NH:20][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=1[CH3:15])[CH2:17][CH2:18][CH3:19] | Cc1ccccc1OS(=O)(=O)C(F)(F)F | CCCCN | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | General procedure B using 55.1 mg (0.229 mmol) of o-tolyltriflate and 34.0 μl (0.344 mmol) of n-butylamine gave 67% yield of N-butyl-2-methylaniline after silica gel chromatograph using 5% ethyl acetate in hexanes. | CCCCNc1ccccc1C | null | 67 | null |
210,520 | ord_dataset-e0a818f9350b46cdb184d2ac404ede9f | null | 1990-01-01T00:06:00 | true | [N:1]1([C:7]2[S:8][CH:9]=[C:10]([C:12](OCC)=[O:13])[N:11]=2)[CH2:6][CH2:5][S:4][CH2:3][CH2:2]1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[N:1]1([C:7]2[S:8][CH:9]=[C:10]([CH2:12][OH:13])[N:11]=2)[CH2:6][CH2:5][S:4][CH2:3][CH2:2]1 | CCOC(=O)c1csc(N2CCSCC2)n1 | null | null | [Al+3] | [H-] | [Li+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | null | null | The reaction described in Preparation 15 was repeated, but using 1.5 g of ethyl 2-(thiomorpholin-4-yl)thiazole -4-carboxylate, 0.26 g of lithium aluminum hydride and 15 ml of tetrahydrofuran, giving the title compound as a colorless powder. | OCc1csc(N2CCSCC2)n1 | null | null | null |
726,870 | ord_dataset-eb4226b4f7644a01a737e7547b70014a | null | 2006-01-01T00:09:00 | true | [CH2:1]([N:8]1[CH2:13][CH:12]2[CH2:14][CH:9]1[CH2:10][N:11]2[CH2:15][C:16]#[N:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>[Ni].N>[CH2:1]([N:8]1[CH2:13][CH:12]2[CH2:14][CH:9]1[CH2:10][N:11]2[CH2:15][CH2:16][NH2:17])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1 | N#CCN1CC2CC1CN2Cc1ccccc1 | null | null | [Ni] | N | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | A solution of 5.74 g (25.3 mmoles) of 140 and 50 mL of NH3 were hydrogenated with 2 g of Raney nickel in a steel autoclave at 100 bar H2 and 100° C. for 2 hours. The catalyst was filtered off with suction and the solution was evaporated and distilled using a bulb tube (boiling point: 135°–145° C. at 0.01 mbar): 5.02 g of 141 as a colorless oil (87% of the theoretical yield). | NCCN1CC2CC1CN2Cc1ccccc1 | null | 85.8 | null |
315,037 | ord_dataset-bd998d3fe946475e835418aaf647c00d | null | 1995-01-01T00:08:00 | true | Cl[C:2](Cl)([C:12]([CH3:14])=[O:13])[C:3]([NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:4].[H][H]>O.C1(C)C=CC=CC=1.[H][H]>[C:3]([NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)(=[O:4])[CH2:2][C:12]([CH3:14])=[O:13] | [H][H] | CC(=O)C(Cl)(Cl)C(=O)Nc1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Cc1ccccc1 | O | null | null | null | null | null | null | null | null | null | null | null | 2.46 g (0.01 mole) of α,α-dichloroacetoacetanilide was dissolved in 20 ml of water and 30 ml of toluene, and dehalogenated with hydrogen using 5% Pd/C as catalyst. Hydrogen was allowed to react until no more would be absorbed. The first equivalent (251 ml at 739 mm pressure and 25° C.) was absorbed in 50 minutes (a rate of about 5 ml/min) whereas the 274 ml (second equivalent) was absorbed at the much slower rate of about 0.9 ml/min. On the basis of the hydrogen absorbed, it was concluded that the dehalogenation had proceeded to remove both chlorines and hence to give acetoacetanilide. This was confirmed by filtering off the catalyst, separating off the water phase and finally isolating the product from the toluene. Obtained were 1.57 g or 89% of acetoacetanilide, mp 79°-84° C. | CC(=O)CC(=O)Nc1ccccc1 | null | null | null |
1,442,867 | ord_dataset-275a3da8f45f4536ad29727f0ef9ba66 | null | 2014-01-01T00:06:00 | true | [Cl:1][C:2]1[S:14][C:5]2=[N:6][C:7]([Cl:13])=[C:8]([C:10](=[O:12])[CH3:11])[CH:9]=[C:4]2[CH:3]=1>C1COCC1>[Cl:1][C:2]1[S:14][C:5]2=[N:6][C:7]([Cl:13])=[C:8]([C@H:10]([OH:12])[CH3:11])[CH:9]=[C:4]2[CH:3]=1 | CC(=O)c1cc2cc(Cl)sc2nc1Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | 25 | 1 | 1-(2,6-Dichlorothieno[2,3-b]pyridin-5-yl)ethanone (3.6 g, 14.63 mmol) was dissolved in THF (100 mL) and ccoled to −55° C. in a dry ice/MeCN bath. To this solution was added a solution of (+)-dip-chloride(tm) (10.32 g, 32.2 mmol) in THF dropwise. The reaction was allowed to warm slowly to rt overnight and quenched by addition of 10 mL of acetone and 50 mL of 50% sat. Na2CO3. The reaction was stirred for 1 h and diluted with 400 mL of ethyl acetate. The organic layer was washed with 2×100 mL of 50% sat Na2CO3, 2×100 mL of water, and 2×100 mL of brine. The reaction was dried over MgSO4, filtered and concentrated. The residue was slurried in 100 mL water/200 mL hexanes for 3 h to form white ppt that was filtered and dried to afford (R)-1-(2,6-dichlorothieno[2,3-b]pyridin-5-yl)ethanol. Enantiomeric excess as determined by chiral HPLC was found to be =99%. 1H NMR (400 MHz, CDCl3) δ 8.19 (d, J=0.8 Hz, 1H), 7.14 (s, 1H), 5.32 (qdd, J=6.3, 3.5, 0.8 Hz, 1H), 2.07 (J=3.5 Hz, 1H), 1.56 (d, J=6.6 Hz, 3H) ppm. | C[C@@H](O)c1cc2cc(Cl)sc2nc1Cl | null | null | null |
1,036,309 | ord_dataset-3af92aec23dc4810b92eb0d8c60023ee | null | 2011-01-01T00:03:00 | true | [O:1]=[C:2]1[N:8]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C@@H:18]([C:29](O)=[O:30])[CH2:19][C:20]3[CH:25]=[C:24]([CH3:26])[C:23]([OH:27])=[C:22]([CH3:28])[CH:21]=3)=[O:16])[CH2:11][CH2:10]2)[CH2:7][CH2:6][C:5]2[CH:32]=[CH:33][CH:34]=[CH:35][C:4]=2[NH:3]1.[CH3:36][N:37]1[CH2:42][CH2:41][CH:40]([CH:43]2[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]2)[CH2:39][CH2:38]1>>[O:1]=[C:2]1[N:8]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C@H:18]([CH2:19][C:20]3[CH:25]=[C:24]([CH3:26])[C:23]([OH:27])=[C:22]([CH3:28])[CH:21]=3)[C:29]([N:46]3[CH2:47][CH2:48][CH:43]([CH:40]4[CH2:39][CH2:38][N:37]([CH3:36])[CH2:42][CH2:41]4)[CH2:44][CH2:45]3)=[O:30])=[O:16])[CH2:11][CH2:10]2)[CH2:7][CH2:6][C:5]2[CH:32]=[CH:33][CH:34]=[CH:35][C:4]=2[NH:3]1 | CN1CCC(C2CCNCC2)CC1 | Cc1cc(C[C@@H](OC(=O)N2CCC(N3CCc4ccccc4NC3=O)CC2)C(=O)O)cc(C)c1O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Prepared analogously to Example 1i from 150 mg (0.31 mmol) (R)-2-(4-hydroxy-3,5-dimethyl-phenyl)-1-carboxy-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate and 62 mg (0.34 mmol) 1-methyl-[4,4′]bipiperidinyl. | Cc1cc(C[C@@H](OC(=O)N2CCC(N3CCc4ccccc4NC3=O)CC2)C(=O)N2CCC(C3CCN(C)CC3)CC2)cc(C)c1O | null | null | null |
903,637 | ord_dataset-46d216f2c4374ef5b9df90427e2a4cd4 | null | 2009-01-01T00:09:00 | true | [C:1](=[O:12])([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])OC(C)(C)C.[CH2:13]([O:15][CH:16]([CH2:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([CH2:34][NH:35][CH3:36])[CH:29]=2)=[CH:24][CH:23]=1)[C:17]([O:19][CH3:20])=[O:18])[CH3:14].C(N(CC)CC)C>ClCCl>[C:8]([O:7][C:1]([CH2:36][NH:35][CH2:34][C:30]1[CH:29]=[C:28]([C:25]2[CH:26]=[CH:27][C:22]([CH2:21][CH:16]([O:15][CH2:13][CH3:14])[C:17]([O:19][CH3:20])=[O:18])=[CH:23][CH:24]=2)[CH:33]=[CH:32][CH:31]=1)=[O:12])([CH3:9])([CH3:10])[CH3:11] | CCOC(Cc1ccc(-c2cccc(CNC)c2)cc1)C(=O)OC | CC(C)(C)OC(=O)OC(C)(C)C | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(CC)CC | ClCCl | null | null | null | null | null | null | null | null | null | 25 | 48 | A solution of 0.4 g (1.9 mmol) of di-tert-butyl carbonate in 5 ml of dichloromethane is added dropwise to a solution of 0.6 g (1.9 mmol) of methyl 2-ethoxy-3-(3′-methylaminomethylbiphenyl-4-yl)propionate and 0.25 ml (1.9 mmol) of triethylamine in 10 ml of dichloromethane. After stirring at room temperature for 48 hours, the medium is washed with water, extracted with dichloromethane, dried over magnesium sulfate, filtered and evaporated to dryness. The residue obtained is purified by chromatography on a column of silica eluted with a 9/1 heptane/ethyl acetate mixture. 0.78 g of methyl 3-{3′-[(tert-butoxycarbonylmethylamino)-methyl]biphenyl-4-yl}-2-ethoxypropionate is obtained in a yield of 85%. | CCOC(Cc1ccc(-c2cccc(CNCC(=O)OC(C)(C)C)c2)cc1)C(=O)OC | null | 96 | null |
76,082 | ord_dataset-8868acadaee548d5802e504148fc3b63 | null | 1981-01-01T00:01:00 | true | [Br:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][NH:18][C:19]1[CH:36]=[CH:35][C:22]([C:23]([N:25]2[CH:29]([C:30]([O:32]CC)=[O:31])[CH2:28][S:27][CH2:26]2)=[O:24])=[CH:21][CH:20]=1>C(=O)(O)[O-].[Na+].CC(C)=O>[Br:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][NH:18][C:19]1[CH:20]=[CH:21][C:22]([C:23]([N:25]2[CH:29]([C:30]([OH:32])=[O:31])[CH2:28][S:27][CH2:26]2)=[O:24])=[CH:35][CH:36]=1 | CCOC(=O)C1CSCN1C(=O)c1ccc(NCCCCCCCCCCCCCCCCBr)cc1 | null | null | O=C([O-])O | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(C)=O | null | null | null | null | null | null | null | null | null | null | null | null | One-tenth mole of 4-(16-bromohexadecylamino)benzoyl chloride hydrochloride in methylene chloride is added to a solution of 0.1 mole of ethyl thiazolidine-4-carboxylate in chloroform containing two equivalents of triethylamine. After 5 hours at 20° C. the solution is filtered and evaporated to a white solid which is recrystallized from acetonitrile to yield 3-[4-(16-bromohexadecylamino)benzoyl]-4-carbethoxythiazolidine. By means of the alkaline hydrolysis method of Example 10, the ethyl ester is converted to the subject carboxylic acid. This acid is also prepared using the procedure of this Example except that the acylation of the thiazolidine-4-carboxylic acid is carried out in aqueous acetone sodium bicarbonate solution. | O=C(O)C1CSCN1C(=O)c1ccc(NCCCCCCCCCCCCCCCCBr)cc1 | null | null | null |
1,063,192 | ord_dataset-ffbef48837674f39816de887b5dc8bae | null | 2011-01-01T00:06:00 | true | [OH:1][C:2]1[CH:36]=[CH:35][C:5]([C:6]([CH2:8][NH:9][C:10]2[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:11]=2[CH:18]2[CH2:27][CH2:26][C:25]3[CH:24]=[C:23]([O:28]C(=O)C(C)(C)C)[CH:22]=[CH:21][C:20]=3[CH2:19]2)=O)=[CH:4][CH:3]=1.Cl[CH2:38][C:39]([N:41]([CH3:43])[CH3:42])=O>>[CH3:42][N:41]([CH3:43])[CH2:39][CH2:38][O:1][C:2]1[CH:36]=[CH:35][C:5]([CH2:6][CH2:8][NH:9][C:10]2[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:11]=2[CH:18]2[CH2:27][CH2:26][C:25]3[CH:24]=[C:23]([OH:28])[CH:22]=[CH:21][C:20]=3[CH2:19]2)=[CH:4][CH:3]=1 | COc1ccc(C2CCc3cc(OC(=O)C(C)(C)C)ccc3C2)c(NCC(=O)c2ccc(O)cc2)c1 | CN(C)C(=O)CCl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Synthesized from pivalic acid 6-{2-[(4-hydroxybenzoyl)methylamino]-4-methoxyphenyl}-5,6,7,8-tetrahydronaphthalen-2-yl ester (25 mg) and 2-chloro-N,N-dimethylacetamide (13 mg) according to an analogous synthetic method to Example 404 and purified by LC-MS, the title compound (5.4 mg) was obtained. | COc1ccc(C2CCc3cc(O)ccc3C2)c(NCCc2ccc(OCCN(C)C)cc2)c1 | null | 22.9 | null |
266,951 | ord_dataset-134cf2fa32ab464880d75db06c38f35a | null | 1993-01-01T00:05:00 | true | [NH2:1][C:2]1[C:3]([F:16])=[CH:4][C:5]2[O:10][CH2:9][C:8](=[O:11])[N:7]([O:12][CH2:13][CH3:14])[C:6]=2[CH:15]=1.[C:17]1([CH3:24])[C:18]([CH3:23])=[CH:19][CH:20]=[CH:21][CH:22]=1>>[CH2:13]([O:12][N:7]1[C:6]2[CH:15]=[C:2]([N:1]3[CH:23]=[C:18]4[C:17]([CH2:22][CH2:21][CH2:20][CH2:19]4)=[CH:24]3)[C:3]([F:16])=[CH:4][C:5]=2[O:10][CH2:9][C:8]1=[O:11])[CH3:14] | CCON1C(=O)COc2cc(F)c(N)cc21 | Cc1ccccc1C | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | 0.25 | A mixture consisting of 6-amino-4-ethoxy-7-fluoro-1,4-benzoxazin-3(4H)-one (1.06 g), 1,2-cyclohexanedicarboxyaldehyde (0.7 g) and xylene (50 ml) was stirred for 15 minutes under heat-refluxing. After the solvent had been distilled off under reduced pressure, the residue was purified through silica-gel chromatography (eluent: hexane/ethyl acetate=19/1) to obtain the aimed 4-ethoxy-7-fluoro-6-(4,5,6,7-tetrahydroisoindole-2-yl)-1,4-benzoxazin-3(4H)-one (1.37 g). nD20 1.5797 | CCON1C(=O)COc2cc(F)c(-n3cc4c(c3)CCCC4)cc21 | null | null | null |
1,534,805 | ord_dataset-8d5c200bca27407ab9febe7598e16458 | null | 2015-01-01T00:01:00 | true | C(O)(C(F)(F)F)=O.[F:8][C:9]1[CH:10]=[C:11]([C@H:17]2[CH2:21][CH2:20][CH2:19][N:18]2C(OC(C)(C)C)=O)[C:12]([O:15][CH3:16])=[N:13][CH:14]=1>C(Cl)Cl>[F:8][C:9]1[CH:10]=[C:11]([C@H:17]2[CH2:21][CH2:20][CH2:19][NH:18]2)[C:12]([O:15][CH3:16])=[N:13][CH:14]=1 | COc1ncc(F)cc1[C@H]1CCCN1C(=O)OC(C)(C)C | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | O=C(O)C(F)(F)F | null | null | null | null | null | null | null | null | null | 25 | 1 | A DCM (12 mL) solution of TFA (11.3 mL, 146 mmol) was added to (R)-tert-butyl 2-(5-fluoro-2-methoxypyridin-3-yl)pyrrolidine-1-carboxylate (4.33 g, 14.6 mmol) and stirred at ambient temperature for 1 hour. The reaction was then concentrated, taken up in EtOAc, then washed with NaHCO3 and brine. The organic phase was dried (MgSO4), filtered, and concentrated, and the crude material was purified by silica column chromatography eluting with a 1-2% 7 N NH3-MeOH/DCM to afford (R)-5-fluoro-2-methoxy-3-(pyrrolidin-2-yl)pyridine as a liquid (1.40 g, 49% yield). | COc1ncc(F)cc1[C@H]1CCCN1 | null | 48.9 | null |
683,507 | ord_dataset-359b8fc87f4244be89d6f02bc5036eac | null | 2005-01-01T00:09:00 | true | [F:1][C:2]([F:15])([F:14])[S:3]([O:6]S(C(F)(F)F)(=O)=O)(=[O:5])=[O:4].N1C=CC=CC=1.O[CH2:23][C:24]([CH3:46])([CH3:45])[O:25][C:26]1[C:27]([CH2:37][CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)=[C:28]2[C:33](=[CH:34][CH:35]=1)[C:32](=[O:36])[CH2:31][CH2:30][CH2:29]2>ClCCl>[F:1][C:2]([F:15])([F:14])[S:3]([O:6][CH2:45][C:24]([CH3:46])([O:25][C:26]1[CH:35]=[CH:34][C:33]2[C:32](=[O:36])[CH2:31][CH2:30][CH2:29][C:28]=2[C:27]=1[CH2:37][CH2:38][C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1)[CH3:23])(=[O:5])=[O:4] | O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F | CC(C)(CO)Oc1ccc2c(c1CCc1ccccc1)CCCC2=O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | c1ccncc1 | ClCCl | null | null | null | null | null | null | null | null | null | 0 | 0.25 | Trifluoromethanesulfonic anhydride (0.12 mL, 0.74 mmol) was added to a solution of pyridine (0.14 mL, 1.77 mmol) in dichloromethane (0.5 mL). The resulting mixture was added over 15 min to an ice-cooled solution of 6-(2-hydroxy-1,1-dimethylethoxy)-5-(2-phenylethyl)-3,4-dihydro-1(2H)-naphthalenone (100 mg, 0.30 mmol) in dichloromethane (0.5 mL). The resulting mixture was stirred for 15 min and was then quenched by the addition of water (2 mL). The mixture was diluted with 1 M aqueous hydrochloric acid (10 mL) and extracted with ethyl acetate (3×5 mL). The combined extracts were washed with 1 M aqueous hydrochloric acid (10 mL), saturated aqueous copper sulfate (3×5 mL), and was then dried (brine, Na2SO4) and concentrated. The residue was purified by dry-flash column chromatography (SiO2, 5-40% ethyl acetate-hexane) to give 2-methyl-2-{[5-oxo-1-(2-phenylethyl)-5,6,7,8-tetrahydro-2-naphthalenyl]oxy}propyl trifluoromethanesulfonate as a colorless oil, 125 mg, 90% yield. NMR spectrum was consistent with structure. MS EI: M+• 470.1376 (M+• 470.1375). | CC(C)(COS(=O)(=O)C(F)(F)F)Oc1ccc2c(c1CCc1ccccc1)CCCC2=O | null | 90 | null |
1,233,343 | ord_dataset-e96f5a2842f14e5380461c234100f05a | null | 2012-01-01T00:12:00 | true | [Br:1][C:2]1[CH:14]=[CH:13][C:5]2[NH:6][C:7](=O)[O:8][C:9]([CH3:11])([CH3:10])[C:4]=2[CH:3]=1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:24])=CC=1>>[Br:1][C:2]1[CH:14]=[CH:13][C:5]2[NH:6][C:7](=[S:24])[O:8][C:9]([CH3:11])([CH3:10])[C:4]=2[CH:3]=1 | CC1(C)OC(=O)Nc2ccc(Br)cc21 | COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The product was prepared, from 6-bromo-4,4-dimethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one and Lawesson's reagent using the procedure of Example 9, as a white solid: mp 221-222.5° C.; 1H-NMR (CDCl3) δ 9.38 (s, 1H, D2O exchangeable), 7.42 (dd, 1H, J=8.5, 2.1 Hz), 7.29 (d, 1H, J=2.0 Hz), 6.76 (d, 1H, J=8.4 Hz), 1.76 (s, 6H); MS (EI) m/z 272 ([M+H]+, 94%), 274 ([M+H]+, 100%). | CC1(C)OC(=S)Nc2ccc(Br)cc21 | null | null | null |
828,267 | ord_dataset-47bd90bf5ec74fcd99ce250a56e18c8f | null | 2008-01-01T00:07:00 | true | [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH2:12][CH:11]([CH2:13]S([O-])(=O)=O)[O:10][N:9]=2)=[CH:4][C:3]=1[F:18].[N-:19]=[N+:20]=[N-:21].[Na+]>CN(C=O)C>[N:19]([CH2:13][CH:11]1[O:10][N:9]=[C:8]([C:5]2[CH:6]=[CH:7][C:2]([Br:1])=[C:3]([F:18])[CH:4]=2)[CH2:12]1)=[N+:20]=[N-:21] | O=S(=O)([O-])CC1CC(c2ccc(Br)c(F)c2)=NO1 | [N-]=[N+]=[N-] | null | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | 80 | 5 | [3-(4-Bromo-3-fluorophenyl)-4,5-dihydroisoxazol-5-yl]methane sulfonate (9.85 g, 28 mmol) was dissolved in dry DMF (100 ml). Sodium azide (2.73 g, 42 mmol) was added and the reaction mixture stirred at 80° C. for 5 hours. The reaction mixture was concentrated in vacuo then azeotroped with xylene (20 ml). The crude product was dissolved in ethyl acetate (100 ml) and washed with water (100 ml). The organic layer was separated, dried over magnesium sulfate, filtered then concentrated in vacuo to yield 8.046 g of the desired compound. | [N-]=[N+]=NCC1CC(c2ccc(Br)c(F)c2)=NO1 | null | 96.1 | null |
142,702 | ord_dataset-84dc0c9e5fb4424687194ef8d14d1c22 | null | 1986-01-01T00:04:00 | true | [Cl:1][C:2]1[CH:20]=[CH:19][C:5]([C:6]([C:8]2[N:12]([CH3:13])[C:11]([CH2:14][C:15](Cl)=[O:16])=[CH:10][C:9]=2[CH3:18])=[O:7])=[CH:4][CH:3]=1.[O-2].[Mg+2].[NH2:23][C@H:24]([C:30]([OH:32])=[O:31])[CH2:25][CH2:26][C:27](=[O:29])[NH2:28].Cl>O1CCOCC1.O>[OH2:7].[Cl:1][C:2]1[CH:20]=[CH:19][C:5]([C:6]([C:8]2[N:12]([CH3:13])[C:11]([CH2:14][C:15]([NH:23][C@H:24]([C:30]([OH:32])=[O:31])[CH2:25][CH2:26][C:27](=[O:29])[NH2:28])=[O:16])=[CH:10][C:9]=2[CH3:18])=[O:7])=[CH:4][CH:3]=1 | Cc1cc(CC(=O)Cl)n(C)c1C(=O)c1ccc(Cl)cc1 | NC(=O)CC[C@H](N)C(=O)O | null | Cl | [Mg+2] | [O-2] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | C1COCCO1 | null | null | null | null | null | null | null | null | null | 25 | 64 | A solution of 30.5 g (0.1 mole) of [5-(4-chlorobenzoyl)-1,4-dimethyl-1H-pyrrol-2-yl]-acetyl chloride in 150 ml of dioxane was added slowly at 0°-5° C. to a suspension of 5.88 g (0.15 mole) of magnesium oxide and 14.3 g (0.1 mole) of L-glutamine in 300 ml of water. The resulting yellow suspension was stirred at room temperature for 64 hours. The mixture was acidified with 1N hydrochloric acid and cooled. The precipitate was collected, washed with water and air dried. It was recrystallized three times from 2-propanol to give 10.8 g of light tan solid which was subjected to chromatography on silica gel. The column was eluted with chloroform:acetic acid:methanol (95:05:4.5). The major compound bearing fraction was concentrated to dryness and the residue recrystallized from acetone, water (2:1) to give 4.5 g (10% yield) of pale yellow crystalline N-{[5-(4-chlorobenzoyl)-1,4-dimethyl-1H-pyrrol-2-yl]-acetyl}-glutamine, hydrate (1:1), m.p. 186°-188° C. | Cc1cc(CC(=O)N[C@@H](CCC(N)=O)C(=O)O)n(C)c1C(=O)c1ccc(Cl)cc1 | null | 20.6 | null |
553,230 | ord_dataset-ec9decb576c4424c9685993f6262bd9c | null | 2002-01-01T00:07:00 | true | [C:1]([C:3]1[C:7]([CH3:8])=[C:6]([C:9]2[CH:14]=[CH:13][N:12]=[CH:11][CH:10]=2)[NH:5][C:4]=1[C:15]1[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=1)#[N:2].C([O-])(O)=[O:22].[Na+]>S(=O)(=O)(O)O>[NH2:2][C:1]([C:3]1[C:7]([CH3:8])=[C:6]([C:9]2[CH:10]=[CH:11][N:12]=[CH:13][CH:14]=2)[NH:5][C:4]=1[C:15]1[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=1)=[O:22] | O=C([O-])O | Cc1c(-c2ccncc2)[nH]c(-c2ccncc2)c1C#N | null | O=S(=O)(O)O | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | 85 | 15 | 3-Cyano-4-methyl-2,5-di(4-pyridyl)-1H-pyrrole (200 mg, 0.77 mmol) was dissolved in sulfuric acid (3 mL) and the mixture was stirred for 15 hours at 85° C. After cooling, fuing sulfuric acid (1 drop) was added to the reaction mixture and stirred for 1 hour at room temperature. The reaction mixture was neutralized by saturated aqueous NaHCO3 solution, and the resulting precipitates were collected by filtration. Recrystallization from EtOH gave the title compound (110 mg, 51% yield). | Cc1c(-c2ccncc2)[nH]c(-c2ccncc2)c1C(N)=O | null | 51 | null |
1,084,360 | ord_dataset-afd812677c134591a99f46ce28de2524 | null | 2011-01-01T00:08:00 | true | [CH2:1]([O:8][C:9]1[C:10]([CH2:15][NH2:16])=[N:11][CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P(Cl)(Cl)(Cl)=O.[CH:22](O)=O>>[CH2:1]([O:8][C:9]1[C:10]2[N:11]([CH:22]=[N:16][CH:15]=2)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1 | O=CO | NCc1ncccc1OCc1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O=P(Cl)(Cl)Cl | null | null | null | null | null | null | null | null | null | null | null | null | This compound is prepared according to the same procedure as in preparation II (stage C) from 2.8 g (13.25 mmol) of 1-[3-(benzyloxy)pyridin-2-yl]methanamine [described in Inorg. Chem., (2003), 42(14), 4401] by formylation with formic acid and then cyclization by reaction with phosphoryl chloride. 1.74 g of a brown oil are obtained. | c1ccc(COc2cccn3cncc23)cc1 | null | null | null |
1,642,528 | ord_dataset-bcc0b01d4f58457a8733b10a099f43ba | null | 2015-01-01T00:10:00 | true | C([O:8][CH2:9][CH:10]1[CH2:17][CH2:16][CH2:15][CH2:14][C:11]21[CH2:13][CH2:12]2)C1C=CC=CC=1.[H][H]>CO.CCOC(C)=O>[CH2:12]1[C:11]2([CH2:14][CH2:15][CH2:16][CH2:17][CH:10]2[CH2:9][OH:8])[CH2:13]1 | [H][H] | c1ccc(COCC2CCCCC23CC3)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOC(C)=O | CO | null | null | null | null | null | null | null | null | null | 25 | 2 | To a solution of 4-((benzyloxy)methyl)spiro[2,5]-octane (0.42 g, 1.8 mmol) in a 5:1 MeOH-EtOAc (12 mL) Pd/C (0.05 g, 5 wt %, 50% wet Degussa type) was added. The flask was fitted with a balloon of hydrogen, and the heterogeneous reaction mixture was stirred for 2 hours under a hydrogen atmosphere at rt. The catalyst solids were filtered off and the filtrate was concentrated under vacuum to give the desired product spyri[2.5]octan-4-ylmethanol as clear oil. 1H NMR (400 MHz, CDCl3) δ 3.74-3.62 (m, 2H), 3.48 (d, J=5.2 Hz, 2H), 1.65-1.59 (m, 2H), 1.51-1.43 (m, 3H), 1.27-1.24 (m, 1H), 1.12-1.11 (m, 1H), 0.96-0.95 (m, 1H), 0.41-0.37 (m, 1H), 0.29-0.17 (m, 3H). MS m/z 123.1 (M−17+1). | OCC1CCCCC12CC2 | null | null | null |
773,515 | ord_dataset-8214eb8444a44dc2900ccb42dbeff15e | null | 2007-01-01T00:05:00 | true | C(ON[C:10]([C@H:12]1[C@@H:17]([OH:18])[C@H:16]([OH:19])[C@@H:15]([OH:20])[CH2:14][N:13]1[S:21]([C:24]1[CH:29]=[CH:28][C:27]([O:30][CH2:31][CH2:32][O:33][CH2:34][CH3:35])=[CH:26][CH:25]=1)(=[O:23])=[O:22])=[O:11])C1C=CC=CC=1.C[OH:37]>[Pd]>[CH2:34]([O:33][CH2:32][CH2:31][O:30][C:27]1[CH:26]=[CH:25][C:24]([S:21]([N:13]2[CH2:14][C@H:15]([OH:20])[C@@H:16]([OH:19])[C@H:17]([OH:18])[C@@H:12]2[C:10]([OH:37])=[O:11])(=[O:22])=[O:23])=[CH:29][CH:28]=1)[CH3:35] | CCOCCOc1ccc(S(=O)(=O)N2C[C@H](O)[C@@H](O)[C@H](O)[C@@H]2C(=O)NOCc2ccccc2)cc1 | CO | null | [Pd] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | 40 | 1 | The above compound (6) (1.66 g) was dissolved in methanol (70 mL) and 10% Pd—C (350 mg) was added, and then the mixture was stirred under a hydrogen atmosphere at 40° C. for one hour. The catalyst was removed by filtration and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel medium pressure column chromatography (chloroform:methanol=10:1→5:1) to obtain the titled compound (815 mg) as a colorless powder. | CCOCCOc1ccc(S(=O)(=O)N2C[C@H](O)[C@@H](O)[C@H](O)[C@@H]2C(=O)O)cc1 | null | null | null |
990,893 | ord_dataset-b6d8835b0c934476a36e6149e7597487 | null | 2010-01-01T00:09:00 | true | [C:1]1([CH2:7][CH2:8][C:9](Cl)=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:12][O:13][C:14]1[CH:15]=[C:16]([C:20]2([OH:26])[CH2:25][CH2:24][CH2:23][NH:22][CH2:21]2)[CH:17]=[CH:18][CH:19]=1>>[OH:26][C:20]1([C:16]2[CH:17]=[CH:18][CH:19]=[C:14]([O:13][CH3:12])[CH:15]=2)[CH2:25][CH2:24][CH2:23][N:22]([C:9](=[O:10])[CH2:8][CH2:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH2:21]1 | O=C(Cl)CCc1ccccc1 | COc1cccc(C2(O)CCCNC2)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The compound of Example 53 was prepared according to the general preparation protocol A from 3-phenyl-propionyl chloride and 3-(3-methoxy-phenyl)-piperidine-3-ol. | COc1cccc(C2(O)CCCN(C(=O)CCc3ccccc3)C2)c1 | null | null | null |
1,100,622 | ord_dataset-af85e6f81c2d49f08086afd6d9e6959c | null | 2011-01-01T00:10:00 | true | [CH2:1]([O:4][C:5]1[C:13]([CH3:14])=[CH:12][C:8]([C:9](O)=[O:10])=[CH:7][C:6]=1[CH3:15])[CH:2]=[CH2:3].S(Cl)([Cl:18])=O>C(Cl)(Cl)Cl>[CH2:1]([O:4][C:5]1[C:13]([CH3:14])=[CH:12][C:8]([C:9]([Cl:18])=[O:10])=[CH:7][C:6]=1[CH3:15])[CH:2]=[CH2:3] | O=S(Cl)Cl | C=CCOc1c(C)cc(C(=O)O)cc1C | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClC(Cl)Cl | null | null | null | null | null | null | null | null | null | null | null | null | To a solution of 4-allyloxy-3,5-dimethyl-benzoic acid (5.26 g, 25.5 mmol) in CHCl3 (75 mL), thionylchloride (7.5 mL, 103 mmol) is added at rt. The mixture is refluxed for 2 h before the solvent is evaporated to give crude 4-allyloxy-3,5-dimethyl-benzoic acid chloride as a brownish oil. To a solution of the acid chloride in DCM (50 mL) hydrazine (75 mL of a 1 M solution in THF) in DCM (250 mL) is added at 0° C. The mixture is stirred at rt for 15 h before it is diluted with diethyl ether and extracted with 1 N aq. HCl (75 mL, then 5×50 mL). The combined aq. extracts are basified by adding 33% aq. KOH solution and extracted with DCM (5×50 mL). The combined DCM extracts are dried over Na2SO4, filtered and evaporated to give 4-allyloxy-3,5-dimethyl-benzoic acid hydrazide (5.39 g) as a white solid; LC-MS: tR=0.71 min, [M+1]+=221.20, 1H NMR (D6-DMSO): δ 2.22 (s, 6H), 4.28-4.37 (m, 2H), 4.39 (s, 2H), 5.19-5.28 (m, 1H), 5.36-5.47 (m, 1H), 6.00-6.15 (m, 1H), 7.49 (s, 2H), 9.55 (s, 1H). | C=CCOc1c(C)cc(C(=O)Cl)cc1C | null | null | null |
110,497 | ord_dataset-406d20cb3f314e2c967b14f55925f895 | null | 1983-01-01T00:10:00 | true | C([O:3][C:4]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[CH2:8][C:7]2[CH:15]=[C:16]([CH2:19][C:20]([O:22]CC)=[O:21])[CH:17]=[CH:18][C:6]=2[CH:5]=1)C.Br>C1(C)C(C)=CC=CC=1>[O:3]=[C:4]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[CH2:8][C:7]2[CH:15]=[C:16]([CH2:19][C:20]([OH:22])=[O:21])[CH:17]=[CH:18][C:6]=2[CH2:5]1 | CCOC(=O)Cc1ccc2c(c1)Cc1ccccc1C(OCC)=C2 | null | null | Br | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Cc1ccccc1C | null | null | null | null | null | null | null | null | null | null | null | null | In 1 ml of xylene was dissolved 0.1 g of ethyl 10-ethoxy-5H-dibenzo[a,d]cycloheptene-3-acetate obtained in Example 13, and 5 ml of 47% hydrobromic acid was added. The mixture was heated under reflux for 2 hours with vigorous stirring. After the reaction, the reaction mixture was cooled, and then worked up in the same way as in Example 19 to afford 0.07 g of 10,11-dihydro-10-oxo-5H-dibenzo[a,d]cycloheptene-3-acetic acid as a colorless crystalline powder (recrystallized from a mixture of methanol and n-hexane) having a melting point of 186° to 187.5° C. | O=C(O)Cc1ccc2c(c1)Cc1ccccc1C(=O)C2 | null | 84.7 | null |
1,708,953 | ord_dataset-3f2a531ffbae4b9eb1048afcd7953beb | null | 2016-01-01T00:04:00 | true | [F:1][CH:2]([F:15])[CH2:3][O:4][C:5]1[CH:6]=[CH:7][C:8]([CH3:14])=[C:9]([C:11](=O)[CH3:12])[CH:10]=1.[CH3:16][C:17]([S@:20]([NH2:22])=[O:21])([CH3:19])[CH3:18]>>[F:1][CH:2]([F:15])[CH2:3][O:4][C:5]1[CH:6]=[CH:7][C:8]([CH3:14])=[C:9]([CH:11]([NH:22][S@@:20]([C:17]([CH3:19])([CH3:18])[CH3:16])=[O:21])[CH3:12])[CH:10]=1 | CC(C)(C)[S@](N)=O | CC(=O)c1cc(OCC(F)F)ccc1C | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The title compound is prepared in 61% yield (400 mg, clear colorless oil) from 1-(5-(2,2-difluoroethoxy)-2-methylphenyl)ethanone (440 mg, 2.1 mmol, Step-4) and (R)-2-methylpropane-2-sulfinamide by the similar manner in Step-4 of Amine-1. | Cc1ccc(OCC(F)F)cc1C(C)N[S@](=O)C(C)(C)C | null | 61 | null |
1,428,896 | ord_dataset-5e6956e6e8c24a168866a253f4a66c6c | null | 2014-01-01T00:05:00 | true | Cl.[NH2:2][CH2:3][CH2:4][N:5]1[C:9]([C:10](OCC)=[O:11])=[CH:8][C:7]2[CH2:15][C:16]([CH3:19])([CH3:18])[CH2:17][C:6]1=2.[O-]CC.[Na+]>C(O)C>[CH3:18][C:16]1([CH3:19])[CH2:15][C:7]2[CH:8]=[C:9]3[N:5]([CH2:4][CH2:3][NH:2][C:10]3=[O:11])[C:6]=2[CH2:17]1 | CCOC(=O)c1cc2c(n1CCN)CC(C)(C)C2 | null | null | CC[O-] | Cl | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | null | null | null | null | null | null | null | null | null | null | 55 | null | A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and nitrogen inlet was purged with nitrogen and charged with crude 110d (˜18 mmol), sodium ethoxide (6.2 g, 92 mmol) and ethanol (120 mL). The mixture was stirred at 55° C. over night. After that time, the reaction mixture was concentrated under reduced pressure and the residue was partitioned between ethyl acetate (200 mL) and water (100 mL). The solution was filtered. The solid was washed with ethyl acetate (15 mL) to give 850 mg of desired product 110e. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (2×100 mL). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure to near dryness. The solution was filtered and the solid (1.44 g) was washed with ethyl acetate (15 mL). The combined solids were dried under vacuum a afford 61% yield (2.3 g) of 110e. | CC1(C)Cc2cc3n(c2C1)CCNC3=O | null | 23.1 | null |
1,580,601 | ord_dataset-380e279f82154dba9e08ab51b3bdd08a | null | 2015-01-01T00:05:00 | true | [C:1]([O:5][C:6]([N:8]([C:13]1[CH:21]=[CH:20][CH:19]=[C:18]2[C:14]=1[CH:15]=[CH:16][N:17]2[CH2:22][C:23]([OH:25])=[O:24])[S:9]([CH3:12])(=[O:11])=[O:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:26][C:27]1[CH:28]=[N+:29]([O-:52])[CH:30]=[C:31]([Cl:51])[C:32]=1[CH2:33][C@@H:34]([C:36]1[CH:41]=[CH:40][C:39]([O:42][CH:43]([F:45])[F:44])=[C:38]([O:46][CH2:47][CH:48]2[CH2:50][CH2:49]2)[CH:37]=1)O.C(Cl)CCl>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:1]([O:5][C:6]([N:8]([C:13]1[CH:21]=[CH:20][CH:19]=[C:18]2[C:14]=1[CH:15]=[CH:16][N:17]2[CH2:22][C:23]([O:25][C@H:34]([C:36]1[CH:41]=[CH:40][C:39]([O:42][CH:43]([F:44])[F:45])=[C:38]([O:46][CH2:47][CH:48]2[CH2:49][CH2:50]2)[CH:37]=1)[CH2:33][C:32]1[C:31]([Cl:51])=[CH:30][N+:29]([O-:52])=[CH:28][C:27]=1[Cl:26])=[O:24])[S:9]([CH3:12])(=[O:11])=[O:10])=[O:7])([CH3:4])([CH3:2])[CH3:3] | [O-][n+]1cc(Cl)c(C[C@H](O)c2ccc(OC(F)F)c(OCC3CC3)c2)c(Cl)c1 | CC(C)(C)OC(=O)N(c1cccc2c1ccn2CC(=O)O)S(C)(=O)=O | null | CN(C)c1ccncc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCCl | ClCCl | null | null | null | null | null | null | null | null | null | null | null | To a solution of 2-(4-(N-(tert-butoxycarbonyl)methylsulfonamido)-1H-indol-1-yl)acetic acid (250 mg, 0.679 mmol) in DCM (10 ml), (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (285 mg, 0.679 mmol), EDC (390 mg, 2.036 mmol) and DMAP (41.5 mg, 0.339 mmol) were added, and the mixture was reacted at room temperature overnight. The mixture was partitioned between DCM and 1N HCl and the aqueous phase was extracted with DCM (3×20 ml); the solvent was removed to give (S)-4-(2-(2-(4-(N-(tert-butoxycarbonyl)-methylsulfonamido)-1H-indol-1-yl)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide (420 mg, 0.545 mmol, 80% yield). MS/ESI+ 770.9 [MH]+. This intermediate was used in the following steps without purification. | CC(C)(C)OC(=O)N(c1cccc2c1ccn2CC(=O)O[C@@H](Cc1c(Cl)c[n+]([O-])cc1Cl)c1ccc(OC(F)F)c(OCC2CC2)c1)S(C)(=O)=O | null | 80.3 | null |
879,064 | ord_dataset-3592bd645cd143ee8274cd0d834ae581 | null | 2009-01-01T00:05:00 | true | C(N1C2=NC=C(C(O)=O)[C:11]([N:12](C)[CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=C2C=N1)C.[C:23]([NH:26][NH:27][C:28]([C:30]1[C:31](NC2CCCC2)=[C:32]2[CH:38]=[N:37][N:36]([CH2:39][CH3:40])[C:33]2=[N:34][CH:35]=1)=[O:29])(=[O:25])[CH3:24]>>[C:23]([NH:26][NH:27][C:28]([C:30]1[CH:31]=[C:32]2[C:38]([N:12]([CH3:11])[CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[N:37][N:36]([CH2:39][CH3:40])[C:33]2=[N:34][CH:35]=1)=[O:29])(=[O:25])[CH3:24] | CCn1ncc2c(N(C)C3CCOCC3)c(C(=O)O)cnc21 | CCn1ncc2c(NC3CCCC3)c(C(=O)NNC(C)=O)cnc21 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Intermediate 53 was prepared from Intermediate 52 using an analogous method to that for Intermediate 4. LCMS showed MH+=361; TRET=1.91 min. | CCn1nc(N(C)C2CCOCC2)c2cc(C(=O)NNC(C)=O)cnc21 | null | null | null |
987,349 | ord_dataset-35b56288528641309a040cc2b6710b61 | null | 2010-01-01T00:08:00 | true | [CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[N:11][C:12]([O:16][CH3:17])=[CH:13][CH:14]=2)[C@@H:9]([NH:18][C:19]2[N:24]=[C:23]([CH2:25][C:26]3[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[C:28]([C:36]([F:39])([F:38])[F:37])[CH:27]=3)[C:22]([N:40]3[CH2:45][CH2:44][CH:43]([C:46]([O:48]CC)=[O:47])[CH2:42][CH2:41]3)=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:51][CH3:52])=[O:5])[CH3:2].[OH-].[K+].Cl>C(O)C.C(OCC)(=O)C>[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[N:11][C:12]([O:16][CH3:17])=[CH:13][CH:14]=2)[C@@H:9]([NH:18][C:19]2[N:24]=[C:23]([CH2:25][C:26]3[CH:31]=[C:30]([C:32]([F:33])([F:34])[F:35])[CH:29]=[C:28]([C:36]([F:37])([F:38])[F:39])[CH:27]=3)[C:22]([N:40]3[CH2:41][CH2:42][CH:43]([C:46]([OH:48])=[O:47])[CH2:44][CH2:45]3)=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:51][CH3:52])=[O:5])[CH3:2] | CCOC(=O)C1CCN(c2cnc(N[C@H]3C[C@@H](CC)N(C(=O)OCC)c4ccc(OC)nc43)nc2Cc2cc(C(F)(F)F)cc(C(F)(F)F)c2)CC1 | null | null | Cl | [K+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOC(C)=O | CCO | null | null | null | null | null | null | null | null | null | 50 | null | To a solution of (2R*,4S*)-4-{[3,5-bis(trifluoromethyl)benzyl]-[5-(4-ethoxycarbonylpiperidin-1-yl)pyrimidin-2-yl]}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (245 mg) in ethanol (2 ml) is added aqueous 2N-potassium hydroxide solution (0.332 ml) and the mixture is heated under reflux at 50° C. for 1 hour. The reaction solution is diluted with ethyl acetate and acidified with 1N-hydrochloric acid. The organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by column chromatography (silica gel; chloroform to chloroform:methanol=90:10) to give (2R*,4S*)-4-{[3,5-bis(trifluoromethyl)benzyl]-[5-(4-carboxypiperidin-1-yl) pyrimidin-2-yl]}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (210 mg). MS (m/z): 711 [M+H]+. | CCOC(=O)N1c2ccc(OC)nc2[C@@H](Nc2ncc(N3CCC(C(=O)O)CC3)c(Cc3cc(C(F)(F)F)cc(C(F)(F)F)c3)n2)C[C@H]1CC | null | 89.1 | null |
217,935 | ord_dataset-67ed03c283094854909157b1038e38e3 | null | 1990-01-01T00:10:00 | true | [Br-:1].[CH3:2][O:3][C:4]1[CH:9]=[CH:8][C:7]([CH:10](O[P+](N(CC)CC)(N(CC)CC)N(CC)CC)[C:11]([F:14])([F:13])[F:12])=[CH:6][CH:5]=1>C(C(C)=O)C(C)C>[Br:1][CH:10]([C:7]1[CH:8]=[CH:9][C:4]([O:3][CH3:2])=[CH:5][CH:6]=1)[C:11]([F:14])([F:13])[F:12] | CCN(CC)[P+](OC(c1ccc(OC)cc1)C(F)(F)F)(N(CC)CC)N(CC)CC | [Br-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(=O)CC(C)C | null | null | null | null | null | null | null | null | null | null | null | null | In a round-bottom flask equipped with reflux condenser, 53.2 g (0.1 mol) [1-(4-methoxyphenyl)-2,2,2-trifluoroethoxy]tris(diethylamino)phosphonium bromide (product from Example 5) were refluxed in 80 ml of methyl isobutyl ketone for 10 minutes. The subsequent distillation gave 22.2 g (83% of yield) of 1-(1-bromo-2,2,2-trifluoroethyl)-4-methoxybenzene (b.p. 108° to 110° C./8 mbar). | COc1ccc(C(Br)C(F)(F)F)cc1 | null | 82.5 | null |
708,196 | ord_dataset-c8069773c1a148aca8ab417108daacc5 | null | 2006-01-01T00:05:00 | true | [Cl:1]N1C(=O)CCC1=O.[Br:9][C:10]([F:25])([F:24])[C:11]([C:17]1[CH:23]=[CH:22][C:20]([NH2:21])=[CH:19][CH:18]=1)([F:16])[C:12]([F:15])([F:14])[F:13]>C(#N)C>[Cl:1][C:22]1[CH:23]=[C:17]([C:11]([F:16])([C:12]([F:15])([F:14])[F:13])[C:10]([Br:9])([F:24])[F:25])[CH:18]=[CH:19][C:20]=1[NH2:21] | Nc1ccc(C(F)(C(F)(F)F)C(F)(F)Br)cc1 | O=C1CCC(=O)N1Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC#N | null | null | null | null | null | null | null | null | null | null | null | null | 18.24 g (0.14 mol) of N-chlorosuccinimide were added at 60° C. to a mixture of 40.0 g (0.12 mol) of 4-(1-bromo-1,1,2,3,3,3-hexafluoro-2-propyl)aniline from Example 6 and 125 ml of acetonitrile, and the resulting mixture was heated to reflux for 3 hours. Subsequently, the solvent was for the most part distilled off, the residue was washed with 100 ml of 1N NaOH solution, the organic phase was dried over sodium sulphate and finally the remaining solvent was removed under reduced pressure. | Nc1ccc(C(F)(C(F)(F)F)C(F)(F)Br)cc1Cl | null | null | null |
728,650 | ord_dataset-eb4226b4f7644a01a737e7547b70014a | null | 2006-01-01T00:09:00 | true | [CH3:1][N:2]([CH3:20])[C:3]1[CH:8]=[CH:7][C:6]([CH2:9][NH:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH3:19])=[CH:13][CH:12]=2)=[CH:5][CH:4]=1.[CH:21]([C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([CH:30]([CH3:32])[CH3:31])[C:25]=1[N:33]=[C:34]=[O:35])([CH3:23])[CH3:22]>>[CH:21]([C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([CH:30]([CH3:31])[CH3:32])[C:25]=1[NH:33][C:34](=[O:35])[N:10]([CH2:9][C:6]1[CH:5]=[CH:4][C:3]([N:2]([CH3:20])[CH3:1])=[CH:8][CH:7]=1)[C:11]1[CH:12]=[CH:13][C:14]([O:17][CH2:18][CH3:19])=[CH:15][CH:16]=1)([CH3:22])[CH3:23] | CC(C)c1cccc(C(C)C)c1N=C=O | CCOc1ccc(NCc2ccc(N(C)C)cc2)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | By the reaction and treatment in the same manner as in Example 2 using [(4-dimethylaminophenyl)methyl](4-ethoxyphenyl)amine (1.0 g) and 2,6-diisopropylphenyl isocyanate (0.89 g) as starting materials, N′-(2,6-diisopropylphenyl)-N-[(4-dimethylaminophenyl)methyl]-N-(4-ethoxyphenyl)urea (0.93 g) was obtained. | CCOc1ccc(N(Cc2ccc(N(C)C)cc2)C(=O)Nc2c(C(C)C)cccc2C(C)C)cc1 | null | 53.1 | null |
118,125 | ord_dataset-3708161f4ba04e959b9a7a8d59fd86e1 | null | 1984-01-01T00:05:00 | true | Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][C:9]1[O:13][N:12]=[C:11]([CH3:14])[CH:10]=1.[Na].[N+:16]([C:19]1[CH:24]=[CH:23][C:22]([OH:25])=[CH:21][CH:20]=1)([O-:18])=[O:17].[I-].[Na+]>O1CCCC1>[CH3:14][C:11]1[CH:10]=[C:9]([CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][O:25][C:22]2[CH:23]=[CH:24][C:19]([N+:16]([O-:18])=[O:17])=[CH:20][CH:21]=2)[O:13][N:12]=1 | O=[N+]([O-])c1ccc(O)cc1 | Cc1cc(CCCCCCCBr)on1 | null | [I-] | [Na+] | [Na] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | 80 | null | A mixture of 3.0 g (0.0115 mole) of 5-(7-bromoheptyl)-3-methylisoxazole and 1.85 g (0.0115 mole) of the sodium salt of 4-nitrophenol in 50 ml of dry tetrahydrofuran containing a few crystals of sodium iodide was heated at 80° C. for 24 hours. The reaction mixture was concentrated in vacuo and the residue triturated with 100 ml of methylene dichloride and 40 ml of water. The organic phase was dried and concentrated, and the residue crystallized from ether to give 3.5 g of 3-methyl-5-[7-(4-nitrophenoxy)heptyl]isoxazole, colorless solid, m.p. 58° C.; MIC vs. polio-2 virus in vitro=1.5 μg/ml. | Cc1cc(CCCCCCCOc2ccc([N+](=O)[O-])cc2)on1 | null | null | null |
900,489 | ord_dataset-de6bce51790e4004a27e1a8f2bcc7ded | null | 2009-01-01T00:08:00 | true | [OH:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[C:13]([C:18]([F:21])([F:20])[F:19])[CH:14]=[CH:15][CH:16]=3)[N:11]=[CH:10][C:9]=2[C:22]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:23])[CH:5]=[CH:6][CH:7]=1.Br[CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([C:38]([F:41])([F:40])[F:39])[CH:33]=1>>[C:24]1([C:22]([C:9]2[CH:10]=[N:11][C:12]3[C:17]([C:8]=2[C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([O:1][CH2:31][C:32]4[CH:37]=[CH:36][CH:35]=[C:34]([C:38]([F:39])([F:40])[F:41])[CH:33]=4)[CH:3]=2)=[CH:16][CH:15]=[CH:14][C:13]=3[C:18]([F:21])([F:19])[F:20])=[O:23])[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1 | FC(F)(F)c1cccc(CBr)c1 | O=C(c1ccccc1)c1cnc2c(C(F)(F)F)cccc2c1-c1cccc(O)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The title compound was prepared from [4-(3-hydroxyphenyl)-8-(trifluoromethyl)quinolin-3-yl](phenyl)methanone and 1-Bromomethyl-3-trifluoromethyl-benzene following the procedure of Example 478: MS (ESI) m/z 552. | O=C(c1ccccc1)c1cnc2c(C(F)(F)F)cccc2c1-c1cccc(OCc2cccc(C(F)(F)F)c2)c1 | null | null | null |
1,565,265 | ord_dataset-4e54080057a44c3887653391e24c90b6 | null | 2015-01-01T00:03:00 | true | [CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][N:2]1[CH2:11][CH:12]([OH:30])[CH2:13][NH:14][C:15](=[O:29])[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([NH:22][CH:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[CH:17]=1.[CH3:31]C(O)=O.C=O.[BH3-]C#N.[Na+]>CO>[CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][N:2]1[CH2:11][CH:12]([OH:30])[CH2:13][NH:14][C:15](=[O:29])[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([N:22]([CH3:31])[CH:23]2[CH2:24][CH2:25][O:26][CH2:27][CH2:28]2)[CH:17]=1 | O=C(NCC(O)CN1CCc2ccccc2C1)c1cccc(NC2CCOCC2)c1 | CC(=O)O | null | C=O | [BH3-]C#N | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | 20 | 2 | To a solution of N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)-3-((tetrahydro-2H-pyran-4-yl)amino)benzamide (300 mg, 0.73 mmol) in MeOH (6 mL) was added AcOH (0.05 mL) and HCHO (548 mg, 7.3 mmol, 40% w/w). The mixture was stirred at 20° C. for 2 h. NaBH3CN (276 mg, 4.38 mmol) was added and the resulting mixture was stirred at 20° C. for 16 h. The reaction solution was concentrated, the residue was washed with water and extracted with EA. The organic layer was concentrated, and the residue was purified by prep-HPLC to give the title compound (105 mg, Yield 33.9%). 1H NMR (CD3OD, 400 MHz): δ 7.37-7.29 (m, 1H), 7.23-7.17 (m, 1H), 7.17-6.97 (m, 6H), 4.18-4.08 (m, 1H), 4.07-3.90 (m, 3H), 3.80-3.68 (m, 2H), 3.62-3.51 (m, 3H), 3.51-3.43 (m, 1H), 2.99-2.79 (m, 7H), 2.75-2.58 (m, 2H), 1.94-1.79 (m, 2H), 1.72-1.59 (m, 2H). LCMS (m/z): 424.1 (M+1). | CN(c1cccc(C(=O)NCC(O)CN2CCc3ccccc3C2)c1)C1CCOCC1 | null | 33.9 | null |
1,146,725 | ord_dataset-68715347640045adb1b09e6a04722b0e | null | 2012-01-01T00:03:00 | true | [CH3:1][O:2][C:3]1[CH:8]=[C:7](B(O)O)[CH:6]=[CH:5][N:4]=1.FC(F)(F)S(O[C:18]1[CH:27]=[CH:26][CH:25]=[C:24]2[C:19]=1[CH2:20][C@H:21]([N:28]([CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH2:22][O:23]2)(=O)=O>>[CH2:36]([N:28]([CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C@H:21]1[CH2:20][C:19]2[C:24](=[CH:25][CH:26]=[CH:27][C:18]=2[C:7]2[CH:6]=[CH:5][N:4]=[C:3]([O:2][CH3:1])[CH:8]=2)[O:23][CH2:22]1)[C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1 | O=S(=O)(Oc1cccc2c1C[C@H](N(Cc1ccccc1)Cc1ccccc1)CO2)C(F)(F)F | COc1cc(B(O)O)ccn1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The title compound was synthesized as described for Intermediate example I-2 in 100% yield, starting from 2-methoxypyridine-4-boronic acid and (3S)-3-(dibenzylamino)-3,4-dihydro-2H-chromen-5-yl trifluoromethanesulfonate; 1H NMR (400 MHz, DMSO-d6) δ ppm 8.22 (d, 1 H), 7.23-7.34 (m, 8 H), 7.09-7.23 (m, 3 H), 6.96 (dd, 1 H), 6.80 (dd, 1 H), 6.70-6.78 (m, 2 H), 4.31-4.37 (m, 1 H), 4.03-4.10 (m, 1 H), 3.91 (s, 3 H), 3.62-3.73 (m, 4 H), 2.90-3.07 (m, 2 H), 2.43-2.49 (m, 1 H); MS (ESI) m/z 437[M+H+]. | COc1cc(-c2cccc3c2C[C@H](N(Cc2ccccc2)Cc2ccccc2)CO3)ccn1 | null | 100 | null |
1,269,445 | ord_dataset-d3580a12b15e46cc91aa73f4f1a4a8cc | null | 2013-01-01T00:03:00 | true | [CH2:1]([O:8][C:9]1[CH:23]=[C:22]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:21]([CH:32]([CH3:34])[CH3:33])=[CH:20][C:10]=1[C:11]([NH:13][N:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1)=S)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.[NH2:36][NH2:37]>C(O)C>[CH2:1]([O:8][C:9]1[CH:23]=[C:22]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:21]([CH:32]([CH3:34])[CH3:33])=[CH:20][C:10]=1[C:11](=[N:36][NH2:37])[NH:13][N:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1 | NN | CC(C)c1cc(C(=S)NN2CCCCC2)c(OCc2ccccc2)cc1OCc1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | O | null | null | null | null | null | null | null | null | null | null | null | 2,4-bis-benzyloxy-5-isopropyl-N-piperidin-1-yl-thiobenzamide (unpurified product of the previous step: F67-03), ethanol (5 mL), hydrazine monohydrate (0.5 mL) was placed in a test tube and heated for 1.5 hours under reflux. After completing the reaction, the reaction mixture was concentrated under reduced pressure while adding toluene several times. The residue thus obtained was subjected to the next step without purification. | CC(C)c1cc(C(=NN)NN2CCCCC2)c(OCc2ccccc2)cc1OCc1ccccc1 | null | null | null |
1,663,831 | ord_dataset-42cd9bc5aae3485f9a58f1527bd3abf0 | null | 2015-01-01T00:11:00 | true | [CH2:1]([C:3]12[CH2:17][CH2:16][C:11]3([O:15][CH2:14][CH2:13][O:12]3)[CH2:10][CH:9]1[CH2:8][CH2:7][O:6][C:5]1[CH:18]=[C:19]([NH2:22])[CH:20]=[CH:21][C:4]2=1)[CH3:2].C1C(=O)N([Br:30])C(=O)C1>C1COCC1>[Br:30][C:20]1[C:19]([NH2:22])=[CH:18][C:5]2[O:6][CH2:7][CH2:8][CH:9]3[CH2:10][C:11]4([O:15][CH2:14][CH2:13][O:12]4)[CH2:16][CH2:17][C:3]3([CH2:1][CH3:2])[C:4]=2[CH:21]=1 | O=C1CCC(=O)N1Br | CCC12CCC3(CC1CCOc1cc(N)ccc12)OCCO3 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | null | 0.08 | A solution of rac-(7aR,11aS)-11a-ethyl-7,7a,8,10,11,11a-hexahydro-6H-spiro[dibenzo[b,d]oxepine-9,2′-[1,3]dioxolan]-3-amine (86, R2=Ethyl) (11.2 g, 37.0 mmol) in THF (370 mL) was cooled to about −10° C. in a salt/ice bath and was then treated with NBS (6.59 g, 37.0 mmol) with stirring for about 5 min. The reaction was quenched by addition of sat. aq. NaHCO3 (250 mL), and the mixture was diluted with EtOAc (350 mL). The aqueous phase was extracted with EtOAc (2×50 mL) and the combined organic phases were washed with brine (350 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified on silica gel (220 g, eluted with 0% to 40% EtOAc in heptane). Collection and concentration of the appropriate fractions gave rac-(7aR,11aS)-2-bromo-11a-ethyl-7,7a,8,10,11,11a-hexahydro-6H-spiro[dibenzo[b,d]oxepine-9,2′-[1,3]dioxolan]-3-amine (87, R2=Ethyl) (13.6 g, 96%) containing about 20% of a minor regioisomer. The material was used directly in Step #4 without further purification. LC/MS, method 3, 2.49 min, MS m/z 382, 384 (M+H)+. | CCC12CCC3(CC1CCOc1cc(N)c(Br)cc12)OCCO3 | null | 96.1 | null |
49,634 | ord_dataset-0bb2e99daa66408fb8dbd6a0781d241c | null | 1978-01-01T00:12:00 | true | Cl[C:2]1[N:3]=[CH:4][C:5]2[C:11](=[O:12])[C:10]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:9][N:8]([CH2:18][CH3:19])[C:6]=2[N:7]=1.[OH:20][CH2:21][CH2:22][N:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1>C1(C)C=CC=CC=1>[OH:20][CH2:21][CH2:22][N:23]1[CH2:28][CH2:27][N:26]([C:2]2[N:3]=[CH:4][C:5]3[C:11](=[O:12])[C:10]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:9][N:8]([CH2:18][CH3:19])[C:6]=3[N:7]=2)[CH2:25][CH2:24]1 | CCOC(=O)c1cn(CC)c2nc(Cl)ncc2c1=O | OCCN1CCNCC1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Cc1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | null | 5.6 g. of 2-chloro-5-oxo-6-carbethoxy-8-ethyl-5,8-dihydro-pyrido(2,3-d)pyrimidine, 5.2 g. of 1-β-hydroxyethyl piperazine and 50 cm3 of toluene are heated under reflux for 2 hours. After cooling, the solution is filtered to remove the hydrochloride which has precipitated, and the organic solution is diluted with its own volume of chloroform, is washed with water and dried (MgSO4). After evaporation, the residue is recrystallised from 40 cm3 of a mixture of isopropanol (1 volume) and isopropyl ether (2 volumes). 5.14 g. (68%) of 2-(4'-β-hydroxyethyl-piperazino)-5-oxo-6-carbethoxy-8-ethylpyrido(2,3-d)pyrimidine are obtained; melting point 172° C. | CCOC(=O)c1cn(CC)c2nc(N3CCN(CCO)CC3)ncc2c1=O | null | 68 | null |
1,402,475 | ord_dataset-7456bda2326f4bebaa874a5474d4cc0d | null | 2014-01-01T00:03:00 | true | [C:1]([O:5][C:6]([N:8]1[CH2:13][C@@H:12]([N:14]([C:19]([C:21]2[N:25]([CH2:26][CH2:27][CH2:28][CH2:29][O:30][CH3:31])[C:24]3[CH:32]=[CH:33][C:34]([F:36])=[CH:35][C:23]=3[N:22]=2)=[O:20])[CH2:15][CH:16]([CH3:18])[CH3:17])[CH2:11][C@@H:10]([C:37](O)=[O:38])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH4+:40].N1(O)C2C=CC=CC=2N=N1.CCN=C=NCCCN(C)C.Cl.C(N(C(C)C)CC)(C)C>CN(C=O)C>[C:37]([C@@H:10]1[CH2:11][C@H:12]([N:14]([C:19]([C:21]2[N:25]([CH2:26][CH2:27][CH2:28][CH2:29][O:30][CH3:31])[C:24]3[CH:32]=[CH:33][C:34]([F:36])=[CH:35][C:23]=3[N:22]=2)=[O:20])[CH2:15][CH:16]([CH3:17])[CH3:18])[CH2:13][N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[CH2:9]1)(=[O:38])[NH2:40] | COCCCCn1c(C(=O)N(CC(C)C)[C@H]2C[C@@H](C(=O)O)CN(C(=O)OC(C)(C)C)C2)nc2cc(F)ccc21 | [NH4+] | null | CCN=C=NCCCN(C)C | Cl | On1nnc2ccccc21 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | CCN(C(C)C)C(C)C | null | null | null | null | null | null | null | null | null | 60 | 3 | (3R,5S)-1-(tert-Butoxycarbonyl)-5-[{[5-fluoro-1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]piperidine-3-carboxylic acid (549 mg), 1H-1,2,3-benzotriazol-1-ol ammonium salt (304 mg) and WSC.HCl (288 mg) were dissolved in DMF (5 ml), diisopropylethylamine (517 μl) was added, and the mixture was stirred at 60° C. for 3 hr. The reaction mixture was cooled to room temperature, concentrated under reduced pressure, and the residue was diluted with aqueous sodium bicarbonate and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, and a fraction eluted with ethyl acetate was concentrated under reduced pressure to give the object product (1.14 g). | COCCCCn1c(C(=O)N(CC(C)C)[C@H]2C[C@@H](C(N)=O)CN(C(=O)OC(C)(C)C)C2)nc2cc(F)ccc21 | null | 208 | null |
1,331,070 | ord_dataset-cfad8b3f00044bcda60a96b019f09872 | null | 2013-01-01T00:08:00 | true | Cl[CH2:2][CH2:3][CH2:4][N:5]1[CH:13]=[N:12][C:11]2[C:6]1=[N:7][CH:8]=[N:9][C:10]=2[NH2:14].[N-:15]=[N+:16]=[N-:17].[Na+]>CN(C=O)C>[N:15]([CH2:2][CH2:3][CH2:4][N:5]1[CH:13]=[N:12][C:11]2[C:6]1=[N:7][CH:8]=[N:9][C:10]=2[NH2:14])=[N+:16]=[N-:17] | [N-]=[N+]=[N-] | Nc1ncnc2c1ncn2CCCCl | null | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | 80 | 24 | A mixture of 9-(3-chloropropyl)adenine (1.9 g, 9 mM) and sodium azide (1.75 g, 27 mM) in DMF was stirred at 80° C. for 24 hours, cooled to room temperature, and filtered. The solid was washed with CH2Cl2. The solvent was removed from the combined filtrates and the residue was taken up in water with sonication. The aqueous layer was extracted with CH2Cl2 (3×60 mL). After removing solvent, the crude product was recrystallized from ethanol to give 9-(3-azidopropyl)adenine as a white crystalline solid in 81% yield. | [N-]=[N+]=NCCCn1cnc2c(N)ncnc21 | null | 81 | null |
1,243,779 | ord_dataset-c544c0c663f54dbea4ddb52ddde7934e | null | 2013-01-01T00:01:00 | true | [CH2:1]([O:3][C:4](=[O:12])[C:5]1[CH:10]=[CH:9][C:8]([NH2:11])=[CH:7][CH:6]=1)[CH3:2].[Cl:13][C:14]1[CH:15]=[C:16]([CH:19]=[CH:20][C:21]=1[F:22])[CH:17]=O>C1(C)C=CC=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>[CH2:1]([O:3][C:4](=[O:12])[C:5]1[CH:10]=[CH:9][C:8]([N:11]=[CH:17][C:16]2[CH:19]=[CH:20][C:21]([F:22])=[C:14]([Cl:13])[CH:15]=2)=[CH:7][CH:6]=1)[CH3:2] | O=Cc1ccc(F)c(Cl)c1 | CCOC(=O)c1ccc(N)cc1 | null | Cc1ccc(S(=O)(=O)O)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Cc1ccccc1 | null | null | null | null | null | null | null | null | null | null | 25 | null | A mixture solution of 4-amino-benzoic acid ethyl ester (16.5 g, 100 mmol), 3-chloro-4-fluoro-benzaldehyde (16.1 g, 100 mmol) and p-toluenesulfonic acid (384 mg, 2.0 mmol) in toluene (200 mL) was heated to reflux for 12 hours. Then the reaction mixture was cooled to room temperature. The solvent was removed in vacuo and the residue was washed with ether to afford 4-[(3-chloro-4-fluoro-benzylidene)-amino]-benzoic acid ethyl ester (30.8 g, quant.) as a pale-white solid: MS calcd. for C16H13ClFNO2 306.74, obsd. (ESI+) [(M+H)+] 306.1. | CCOC(=O)c1ccc(N=Cc2ccc(F)c(Cl)c2)cc1 | null | 100.7 | null |
1,712,506 | ord_dataset-3f2a531ffbae4b9eb1048afcd7953beb | null | 2016-01-01T00:04:00 | true | [CH2:1]([O:4][N:5]([C@H:18]1[CH2:23][N:22](C(OC(C)(C)C)=O)[C@H:21]([C:31]([O:33][CH3:34])=[O:32])[CH:20]=[C:19]1[CH3:35])[S:6]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[N+:15]([O-:17])=[O:16])(=[O:8])=[O:7])[CH:2]=[CH2:3]>C(Cl)Cl.[Br-].[Zn+2].[Br-]>[CH2:1]([O:4][N:5]([C@H:18]1[CH2:23][NH:22][C@H:21]([C:31]([O:33][CH3:34])=[O:32])[CH:20]=[C:19]1[CH3:35])[S:6]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[N+:15]([O-:17])=[O:16])(=[O:8])=[O:7])[CH:2]=[CH2:3] | C=CCON([C@H]1CN(C(=O)OC(C)(C)C)[C@H](C(=O)OC)C=C1C)S(=O)(=O)c1ccccc1[N+](=O)[O-] | null | null | [Br-] | [Zn+2] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | null | 8 | To a solution of (2S,5R)-1-tert-butyl 2-methyl 5-(N-(allyloxy)-2-nitrophenylsulfonamido)-4-methyl-5,6-dihydropyridine-1,2(2H)-dicarboxylate (Intermediate 27, 2.06 g, 4.03 mmol) in DCM (20 mL) at room temperature was added zinc bromide (0.648 mL, 12.08 mmol). After stirring overnight, the reaction mixture was diluted with dichloromethane and washed with saturated sodium bicarbonate and brine. The organics were dried over magnesium sulfate, filtered and concentrated to afford the desired product (1.650 g, 100%) as a light yellow foam. | C=CCON([C@H]1CN[C@H](C(=O)OC)C=C1C)S(=O)(=O)c1ccccc1[N+](=O)[O-] | null | 99.5 | null |
1,619,716 | ord_dataset-35c51552812941cda45194a013d34bb9 | null | 2015-01-01T00:08:00 | true | [NH2:1][C:2]1[C:3]([C:13]([C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)=O)=[CH:4][C:5]([Cl:12])=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2.[CH3:22][NH:23][S:24](Cl)(=[O:26])=[O:25].[BH4-].[Na+]>N1C=CC=CC=1>[Cl:12][C:5]1[C:6]2[C:11]([C:2]3[NH:1][S:24](=[O:26])(=[O:25])[N:23]([CH3:22])[CH:13]([C:15]4[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=4)[C:3]=3[CH:4]=1)=[N:10][CH:9]=[CH:8][CH:7]=2 | Nc1c(C(=O)c2ccc(F)cc2)cc(Cl)c2cccnc12 | CNS(=O)(=O)Cl | null | [BH4-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | c1ccncc1 | null | null | null | null | null | null | null | null | null | null | null | null | In a similar fashion using route 27 general procedure 70, (8-amino-5-chloro-quinolin-7-yl)-(4-fluoro-phenyl)-methanone 400 (105 mg, 0.34 mmol), N-methylsulfamoyl chloride 213 (135 mg, 1.0 mmol) and NaBH4 (14 mg, 0.34 mmol) in pyridine (4 ml) gave the title compound (57 mg, 44%) after purification by preparative HPLC (acidic conditions 1). | CN1C(c2ccc(F)cc2)c2cc(Cl)c3cccnc3c2NS1(=O)=O | null | 44.4 | null |
200,367 | ord_dataset-31f00a039ca0424788e5e1970d25a8fd | null | 1989-01-01T00:12:00 | true | F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1.[CH3:11][C@H:12]1[CH2:17][NH:16][C@@H:15]([CH3:18])[CH2:14][NH:13]1.C(=O)(O)[O-].[Na+]>C(O)CCCC>[N+:8]([C:5]1[CH:6]=[CH:7][C:2]([N:13]2[CH2:14][C@H:15]([CH3:18])[NH:16][CH2:17][C@@H:12]2[CH3:11])=[CH:3][CH:4]=1)([O-:10])=[O:9] | O=[N+]([O-])c1ccc(F)cc1 | C[C@H]1CN[C@@H](C)CN1 | null | O=C([O-])O | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCCCCO | null | null | null | null | null | null | null | null | null | null | null | null | A mixture of 4-fluoronitrobenzene (30.34 g, 0.22 mole), cis-2,5-dimethylpiperazine (25 g, 0.22 mole) and sodium bicarbonate (24 g, 0.28 mole) in n-pentanol (150 ml) was heated under nitrogen at 90°-100° for 18 hours. After filtration, the n-pentanol was removed under reduced pressure and the residue was partitioned between methylene chloride and water. The organic phase was separated, washed again with water, dried over magnesium sulphate, and concentrated under reduced pressure. The residue was triturated with ice water to yield a yellow solid. The solid was filtered off and dried to yield the title compound, m.p. 93°-4° (37 g, 71%). | C[C@H]1CN(c2ccc([N+](=O)[O-])cc2)[C@@H](C)CN1 | null | null | null |
1,315,445 | ord_dataset-2d6edb8ffd434003bb508360153bd9bb | null | 2013-01-01T00:07:00 | true | [CH2:1]([NH:4][CH2:5][CH2:6][CH3:7])[CH2:2][CH3:3].Cl[C:9]1[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][N:10]=1>C(#N)C.O>[N+:15]([C:12]1[CH:13]=[CH:14][C:9]([N:4]([CH2:5][CH2:6][CH3:7])[CH2:1][CH2:2][CH3:3])=[N:10][CH:11]=1)([O-:17])=[O:16] | CCCNCCC | O=[N+]([O-])c1ccc(Cl)nc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC#N | O | null | null | null | null | null | null | null | null | null | null | null | N,N-dipropylamine (3 ml, 22 mmol) was added to a solution of 2-chloro-5-nitropyridine (500 mg, 3.15 mmol) in acetonitrile (7 ml) and heated to reflux overnight. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was then washed with water, brine and dried. Evaporation to dryness gave (5-nitro-pyridin-2-yl)-dipropylamine (630 mg, 90%) as oil. | CCCN(CCC)c1ccc([N+](=O)[O-])cn1 | null | 89.6 | null |
1,767,230 | ord_dataset-0b32b90cc77b4a3db47ad263e0bbc1a8 | null | 2016-01-01T00:09:00 | true | [C:1]([O:9][CH2:10][C@@H:11]1[CH2:15][C@@H:14]([N:16]=[N+]=[N-])[C@H:13]([N:19]2[C:23]3[N:24]=[C:25]([NH2:29])[NH:26][C:27](=[O:28])[C:22]=3[S:21][C:20]2=[O:30])[O:12]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>C1COCC1>[C:1]([O:9][CH2:10][C@@H:11]1[CH2:15][C@@H:14]([NH2:16])[C@H:13]([N:19]2[C:23]3[N:24]=[C:25]([NH2:29])[NH:26][C:27](=[O:28])[C:22]=3[S:21][C:20]2=[O:30])[O:12]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1 | [N-]=[N+]=N[C@@H]1C[C@@H](COC(=O)c2ccccc2)O[C@H]1n1c(=O)sc2c(=O)[nH]c(N)nc21 | null | null | c1ccc(P(c2ccccc2)c2ccccc2)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | O | null | null | null | null | null | null | null | null | null | 80 | 1 | To a solution of compound [(2S,4R,5R)-5-(5-amino-2,7-dioxo-6H-thiazolo[4,5-d]pyrimidin-3-yl)-4-azido-tetrahydrofuran-2-yl]methyl benzoate (compound 33b, 200 mg, 0.466 mmoL) and triphenylphosphine (364 mg, 1.39 mmoL) in THF (10 mL) was added water (0.5 mL) at room temperature. After being stirred at 80° C. for 1 hour, the reaction was filtered and the filtrate was concentrated in vacuo to afford 80 mg crude product of [(2S,4R,5R)-4-amino-5-(5-amino-2,7-dioxo-6H-thiazolo[4,5-d]pyrimidin-3-yl)tetrahydrofuran-2-yl]methyl benzoate (compound 33c), which was used in next step directly. MS obsd. (ESI+) [(M+H)+]: 404. | Nc1nc2c(sc(=O)n2[C@@H]2O[C@H](COC(=O)c3ccccc3)C[C@H]2N)c(=O)[nH]1 | null | 42.6 | null |
462,138 | ord_dataset-5ca9db262dd24c5a9315cdc8ef055b7e | null | 2000-01-01T00:04:00 | true | CC(C)(C)C([N:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]([C:14]2[C:15](=[O:33])[NH:16][C:17](=[O:32])[C:18]=2[C:19]2[C:27]3[C:22](=[CH:23][C:24]([N+:28]([O-:30])=[O:29])=[CH:25][CH:26]=3)[N:21]([CH3:31])[CH:20]=2)=[CH:6]1)=O.O(C)[Na]>CO>[NH:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]([C:14]2[C:15](=[O:33])[NH:16][C:17](=[O:32])[C:18]=2[C:19]2[C:27]3[C:22](=[CH:23][C:24]([N+:28]([O-:30])=[O:29])=[CH:25][CH:26]=3)[N:21]([CH3:31])[CH:20]=2)=[CH:6]1 | Cn1cc(C2=C(c3cn(C(=O)C(C)(C)C)c4ccccc34)C(=O)NC2=O)c2ccc([N+](=O)[O-])cc21 | null | null | CO[Na] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | 25 | 1 | 1.7 g (3.61 mmol) of 3-[1-(2,2-dimethyl-propionyl)-1H-indol-3-yl]-4-(1-methyl-6-nitro-1H-indol-3-yl)-pyrrole-2,5-dione (4) from Step E above in 60 ml of methanol was treated with 5.6 ml (8.96 mmol) of a 1.6 molar solution of NaOCH3 in methanol. The reaction was stirred at room temperature for 1 hour, poured in 2N-HCl/ice and extracted with ethyl acetate. The organic extracts were dried on anhydrous MgSO4 and concentrated to yield, after chromatographic purification, 394.7 mg (28%) of 3-(1H-indol-3-yl)-4-(1-methyl-6-nitro-1H-indol-3-yl)-pyrrole-2,5-dione (I) as a red solid mp>280° C. MS: (M+), m/z 386. | Cn1cc(C2=C(c3c[nH]c4ccccc34)C(=O)NC2=O)c2ccc([N+](=O)[O-])cc21 | null | null | null |
198,351 | ord_dataset-f6fafbb8ce5f4ef099be3a772075ec97 | null | 1989-01-01T00:10:00 | true | [C:1]([N:5]1[C:10](=[O:11])[C:9]([CH3:12])=[C:8](Cl)[CH:7]=[N:6]1)([CH3:4])([CH3:3])[CH3:2].[SH-:14].[Na+]>C(O)C>[C:1]([N:5]1[C:10](=[O:11])[C:9]([CH3:12])=[C:8]([SH:14])[CH:7]=[N:6]1)([CH3:4])([CH3:3])[CH3:2] | [SH-] | Cc1c(Cl)cnn(C(C)(C)C)c1=O | null | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | null | null | null | null | null | null | null | null | null | null | 0 | null | To 75ml of ethanol were added 17.0 g (0.085 mol) of 2-tert.-butyl-5-chloro-4-methyl-3(2H)-pyridazinone and 8.5 g (0.106 mol) of 70% sodium hydrosulfide, and the mixture was stirred under reflux for 4 hours. After cooling, the mixture was poured into 300 ml of ice-water and extracted with 200 ml of ethyl ether. The ether layer was washed with 100 ml of water and dried over anhydrous sodium sulfate. The solvent was then distilled off therefrom to give 16.3 g of a crude product. | Cc1c(S)cnn(C(C)(C)C)c1=O | null | 96.7 | null |
1,730,595 | ord_dataset-36057d699ac5449e9c37eb99abf78b03 | null | 2016-01-01T00:05:00 | true | COC1C=CC(C[N:8]([CH2:30][C:31]2[N:32]=[N:33][N:34]([CH3:36])[CH:35]=2)[C:9]2[C:10](=[O:29])[N:11]([CH3:28])[N:12]=[C:13]([O:15][CH2:16][C@H:17]3[CH2:19][C@@H:18]3[C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][N:21]=3)[CH:14]=2)=CC=1.C([O-])(O)=O.[Na+].[C:44]([OH:50])([C:46]([F:49])([F:48])[F:47])=[O:45]>>[CH3:27][O:26][C:23]1[CH:24]=[CH:25][C:20]([C@H:18]2[CH2:19][C@@H:17]2[CH2:16][O:15][C:13]2[CH:14]=[C:9]([NH:8][CH2:30][C:31]3[N:32]=[N:33][N:34]([CH3:36])[CH:35]=3)[C:10](=[O:29])[N:11]([CH3:28])[N:12]=2)=[N:21][CH:22]=1.[C:44]([OH:50])([C:46]([F:49])([F:48])[F:47])=[O:45] | COc1ccc(CN(Cc2cn(C)nn2)c2cc(OC[C@H]3C[C@@H]3c3ccc(OC)cn3)nn(C)c2=O)cc1 | null | null | O=C([O-])O | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O=C(O)C(F)(F)F | null | null | null | null | null | null | null | null | null | null | null | null | A solution of 4-((4-methoxybenzyl)((1-methyl-1H-1,2,3-triazol-4-yl)methyl)amino)-6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyridazin-3(2H)-one (55 mg, 0.11 mmol) in TFA (2 mL) was stirred at room temperature for 2 h, then pH was adjusted to 7˜8 with saturated NaHCO3 solution. Extracted with EtOAc (20 mL*3), washed with H2O and brine, and concentrated. The residue was purified by Prep-HPLC (CH3CN in 0.05% TFA/H2O 30-95% v/v as mobile phase) to give title compound as a TFA salt, the structure was confirmed by NOE. ESI-MS: 398.2 (M+H)+. 1H NMR (400 MHz, MeOD) δ 8.34 (d, 1H), 8.03 (dd, 1H), 7.86 (s, 1H), 7.80 (d, 1H), 5.88 (s, 1H), 4.47 (s, 2H), 4.30 (dd, 1H), 4.11 (dd, 1H), 4.06 (s, 3H), 4.01 (s, 3H), 3.62 (s, 3H), 2.36-2.32 (m, 1H), 2.01-1.96 (m, 1H), 1.41-1.41 (m, 2H). | COc1ccc([C@H]2C[C@@H]2COc2cc(NCc3cn(C)nn3)c(=O)n(C)n2)nc1 | null | null | null |
898,234 | ord_dataset-de6bce51790e4004a27e1a8f2bcc7ded | null | 2009-01-01T00:08:00 | true | Cl.[N:2]1([C:8]([C:10]2([C:16]#[N:17])[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[O:9])[CH2:7][CH2:6][O:5][CH2:4][CH2:3]1.[CH2:18]([S:21](Cl)(=[O:23])=[O:22])[CH2:19][CH3:20].[OH-].[Na+]>CCN(C(C)C)C(C)C.C(Cl)Cl>[N:2]1([C:8]([C:10]2([C:16]#[N:17])[CH2:15][CH2:14][N:13]([S:21]([CH2:18][CH2:19][CH3:20])(=[O:23])=[O:22])[CH2:12][CH2:11]2)=[O:9])[CH2:3][CH2:4][O:5][CH2:6][CH2:7]1 | CCCS(=O)(=O)Cl | N#CC1(C(=O)N2CCOCC2)CCNCC1 | null | Cl | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(C(C)C)C(C)C | ClCCl | null | null | null | null | null | null | null | null | null | 25 | 1 | To a solution of 4-(morpholin-4-ylcarbonyl)piperidine-4-carbonitrile hydrochloride (I-3) (10.40 g, 40 mmole) in DIEA-DCM (1:4, 200 mL) was added n-C3H7SO2Cl (6.28 g, 44 mmole) at 0° C. The resultant mixture was stirred for 1 h at 0° C. After this time, LCMS indicated that the reaction was complete. 2N NaOH (60 mL) was added to the reaction. The resultant reaction mixture was stirred for 1 h at rt. After this time, the DCM layer was separated. The aqueous solution was extracted with DCM (3×150 mL). The combined DCM solution was washed with brine, dried over MgSO4, filtered, and concentrated to afford the title compound (I-4) which was pure enough for next step reaction. Analytical LCMS: single peak (214 nm), 2.406 min. | CCCS(=O)(=O)N1CCC(C#N)(C(=O)N2CCOCC2)CC1 | null | null | null |
989,951 | ord_dataset-b6d8835b0c934476a36e6149e7597487 | null | 2010-01-01T00:09:00 | true | C(OC([NH:8][C:9]1[CH:31]=[CH:30][C:12]([O:13][C:14]2[CH:19]=[CH:18][N:17]=[C:16]3[CH:20]=[C:21]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][N+:24]=4[O-:29])[S:22][C:15]=23)=[C:11]([F:32])[CH:10]=1)=O)(C)(C)C.C(Cl)Cl.C(O)(C(F)(F)F)=O.[C:43]1([CH2:49][C:50]([N:52]=[C:53]=[S:54])=[O:51])[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>>[F:32][C:11]1[CH:10]=[C:9]([NH:8][C:53]([NH:52][C:50](=[O:51])[CH2:49][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)=[S:54])[CH:31]=[CH:30][C:12]=1[O:13][C:14]1[CH:19]=[CH:18][N:17]=[C:16]2[CH:20]=[C:21]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][N+:24]=3[O-:29])[S:22][C:15]=12 | CC(C)(C)OC(=O)Nc1ccc(Oc2ccnc3cc(-c4cccc[n+]4[O-])sc23)c(F)c1 | O=C(Cc1ccccc1)N=C=S | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | O=C(O)C(F)(F)F | null | null | null | null | null | null | null | null | null | 25 | 1 | A mixture of 432 (243 mg, 0.53 mmol) in 3:1 mixture of DCM/TFA (8 mL) was stirred at room temperature for 1 hour and concentrated under reduced pressure. The resultant solid was dissolved in 1:1 mixture of EtOH/toluene (10 mL) and treated with 2-phenylacetyl isothiocyanate (140 mg, 0.8 mmol). The reaction mixture was stirred for 1 hour at room temperature and concentrated. The residue was purified by flash chromatography using the gradient 0-20% MeOH in EtOAc as an eluent yielding 430 (101 mg, 36% yield). MeOH-d4/CDCl3 (1:1) 8.5 (d, 1H, J=5.4 Hz), 8.38 (m, 3H), 8.0 (d, 1H, 11.9 Hz), 7.62 (t, 1H, J=7.7 Hz), 7.45 (m, 2H), 7.2-7.4 (m, 6H), 6.64 (5.1 Hz), 3.75 (s, 2H). LCMS: (M+H) 531.2. | O=C(Cc1ccccc1)NC(=S)Nc1ccc(Oc2ccnc3cc(-c4cccc[n+]4[O-])sc23)c(F)c1 | null | 35.9 | null |
337,229 | ord_dataset-65c44df6676d4ce3a1874db5d7958ca9 | null | 1996-01-01T00:08:00 | true | Cl[C:2]1[N:7]=[C:6]([NH:8][CH2:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH:5]=[C:4]([NH:14][CH2:15][C:16]([CH3:19])([CH3:18])[CH3:17])[N:3]=1.[NH:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1>>[CH3:17][C:16]([CH3:19])([CH3:18])[CH2:15][NH:14][C:4]1[CH:5]=[C:6]([NH:8][CH2:9][C:10]([CH3:13])([CH3:12])[CH3:11])[N:7]=[C:2]([N:20]2[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)[N:3]=1 | C1CNCCN1 | CC(C)(C)CNc1cc(NCC(C)(C)C)nc(Cl)n1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The reaction of 2-chloro-4,6-bis(2,2-dimethylpropylamino)pyrimidine with piperazine as described in Example 4 leads to the title product in a yield of 78.3%, m.p.: 132°-136° C. | CC(C)(C)CNc1cc(NCC(C)(C)C)nc(N2CCNCC2)n1 | null | 78.3 | null |
1,515,821 | ord_dataset-8c74302143c04eb9983e4b3a7ead2d72 | null | 2014-01-01T00:12:00 | true | [OH:1][CH2:2][C:3]1[O:7][N:6]=[C:5]([C:8](=[O:10])[CH3:9])[CH:4]=1.[C:11](=O)([O-])[O-].[Cs+].[Cs+].CI>C1COCC1>[CH3:11][O:1][CH2:2][C:3]1[O:7][N:6]=[C:5]([C:8](=[O:10])[CH3:9])[CH:4]=1 | CC(=O)c1cc(CO)on1 | O=C([O-])[O-] | null | [Cs+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | CI | null | null | null | null | null | null | null | null | null | 60 | null | To a solution of 1-[5-(hydroxymethyl)-1,2-oxazol-3-yl]ethanone (1.00 g, 7.09 mmol) in dry THF (20 mL) under an atmosphere of nitrogen was introduced cesium carbonate (2.31 g, 7.09 mmol) and methyl iodide (5.03 g, 35.43 mmol). The reaction mixture was warmed to 60° C. for 16 hr, cooled to RT and the solids removed by filtration. The filtrate was re-treated with additional cesium carbonate (4.31 g, 13.23 mmol) and methyl iodide (9.59 g, 67.58 mmol) and warmed to 60° C. for 34 hr. After cooling to RT, the reaction mixture was filtered, concentrated in vacuo and the residue re-dissolved in EtOAc (50 mL). The EtOAc solution was washed with water (25 mL), brine (25 mL), dried (Na2SO4) and filtered. After concentrating the filtrate in vacuo, the residual oil was purified by silica gel flash column chromatography (95:5-50:50 gradient of heptane/EtOAc) to furnish the title compound as a colorless oil: 1H NMR (500 MHz, CDCl3) delta 2.66 (3H, s), 3.44 (3H, s), 4.59 (2H, s), 6.64 (1H, s). | COCc1cc(C(C)=O)no1 | null | null | null |
1,766,896 | ord_dataset-0b32b90cc77b4a3db47ad263e0bbc1a8 | null | 2016-01-01T00:09:00 | true | [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8](O)[C:9]2[C:18]3[C:17](=[O:19])[N:16]([CH2:20][CH2:21][CH2:22][O:23][CH:24]4CCCC[O:25]4)[C:15](=[O:30])[N:14]([CH3:31])[C:13]=3[N:12]=[CH:11][C:10]=2[O:32][C:33]2[CH:34]=[N:35][CH:36]=[CH:37][CH:38]=2)=[CH:4][CH:3]=1>C(O)=O.[Zn]>[CH:24]([O:23][CH2:22][CH2:21][CH2:20][N:16]1[C:17](=[O:19])[C:18]2[C:9]([CH2:8][C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=3)=[C:10]([O:32][C:33]3[CH:34]=[N:35][CH:36]=[CH:37][CH:38]=3)[CH:11]=[N:12][C:13]=2[N:14]([CH3:31])[C:15]1=[O:30])=[O:25] | Cn1c(=O)n(CCCOC2CCCCO2)c(=O)c2c(C(O)c3ccc(Cl)cc3)c(Oc3cccnc3)cnc21 | null | null | [Zn] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O=CO | null | null | null | null | null | null | null | null | null | null | 50 | null | To a solution of 5-((4-chlorophenyl)(hydroxy)methyl)-1-methyl-6-(pyridin-3-yloxy)-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (71 mg, 0.128 mmol) in HCOOH (3 mL) was added Zn dust (40.9 mg, 0.641 mmol). The reaction was heated at 50° C. for 2 h, cooled and filtered. The filtrate was concentrated to a residue which was purified by Prep TLC eluted with PE/EA (1:1) (three times) to give 3-(5-(4-chlorobenzyl)-1-methyl-2,4-dioxo-6-(pyridin-3-yloxy)-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate (10.3 mg, 16.7% yield) as an oil. LCMS: MH+ 481 and TR=1.399 min. | Cn1c(=O)n(CCCOC=O)c(=O)c2c(Cc3ccc(Cl)cc3)c(Oc3cccnc3)cnc21 | null | 16.7 | null |
851,304 | ord_dataset-171b840ae6e84e45bab43b987d09f5c7 | null | 2008-01-01T00:11:00 | true | [CH3:1][C:2]1([CH3:22])[CH:6]([C:7]2[CH:12]=[CH:11][C:10]([CH3:13])=[CH:9][CH:8]=2)[C:5]2[C:14]([CH3:21])=[C:15]([NH2:20])[C:16]([CH3:19])=[C:17]([CH3:18])[C:4]=2[O:3]1.[F:23][C:24]1[CH:32]=[CH:31][C:27]([C:28](Cl)=[O:29])=[CH:26][CH:25]=1>C(OCC)(=O)C.CCCCCC>[F:23][C:24]1[CH:32]=[CH:31][C:27]([C:28]([NH:20][C:15]2[C:16]([CH3:19])=[C:17]([CH3:18])[C:4]3[O:3][C:2]([CH3:22])([CH3:1])[CH:6]([C:7]4[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][CH:12]=4)[C:5]=3[C:14]=2[CH3:21])=[O:29])=[CH:26][CH:25]=1 | Cc1ccc(C2c3c(C)c(N)c(C)c(C)c3OC2(C)C)cc1 | O=C(Cl)c1ccc(F)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOC(C)=O | CCCCCC | null | null | null | null | null | null | null | null | null | null | null | By using 2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-amine and 4-fluorobenzoyl chloride, the title compound was synthesized according to Example 1b. Yield: 43%. Melting point: 148-120° C. (Ethyl acetate-hexane) | Cc1ccc(C2c3c(C)c(NC(=O)c4ccc(F)cc4)c(C)c(C)c3OC2(C)C)cc1 | null | 43 | null |
973,820 | ord_dataset-f886e51ba1484c76a94bce1482f1eab9 | null | 2010-01-01T00:07:00 | true | C(O[C:8]1[CH:13]=[CH:12][C:11]([C:14](=[O:24])[C:15]2[CH:20]=[CH:19][C:18]([N+:21]([O-])=O)=[CH:17][CH:16]=2)=[CH:10][C:9]=1[N+:25]([O-])=O)(=O)CC([O-])=O.Cl.[CH3:29][CH2:30][OH:31]>C(Cl)(Cl)Cl>[NH2:21][C:18]1[CH:17]=[CH:16][C:15]([C:14]([C:11]2[CH:10]=[C:9]3[C:8]([CH2:29][C:30](=[O:31])[NH:25]3)=[CH:13][CH:12]=2)=[O:24])=[CH:20][CH:19]=1 | O=C([O-])CC(=O)Oc1ccc(C(=O)c2ccc([N+](=O)[O-])cc2)cc1[N+](=O)[O-] | CCO | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClC(Cl)Cl | null | null | null | null | null | null | null | null | null | null | 25 | null | [2-Nitro-4-(4-nitrobenzoyl)phenyl] malonate (4.15 g, 9.61 mmol) was dissolved in EtOH (24 mL) after which Sn powder (9.16 g, 77 mmol) was added followed by dropwise addition of concentrated HCl(aq) (26 mL). The reaction mixture was allowed to reflux for 3 hours, filtered while hot and then allowed to cool to room temperature. The cooled reaction mixture was diluted with CHCl3 (400 mL) and then extracted once with H2O (400 mL). The aqueous layer was then neutralized with NaHCO3 (pH=7) and then extracted with a 95% EtOAc/5% i-prOH solution (3×400 mL). The organic layers were combined and dried over anhydrous Na2SO4. The solution was then concentrated in vacuo affording the 6-(4-Amino-benzoyl)-1,3-dihydro-indol-2-one in 51% yield (1.24 g, 4.90 mmol). | Nc1ccc(C(=O)c2ccc3c(c2)NC(=O)C3)cc1 | null | 51 | null |
433,450 | ord_dataset-386da077ab2340638cada986e2ef0770 | null | 1999-01-01T00:07:00 | true | [NH2:1][C:2]1[N:7]=[C:6]2[C:8]([CH:11]3[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]3)=[CH:9][NH:10][C:5]2=[CH:4][CH:3]=1.[C:18]([C:20]1[CH:21]=[C:22]([CH:26]=[CH:27][CH:28]=1)[C:23](Cl)=[O:24])#[N:19]>>[C:18]([C:20]1[CH:21]=[C:22]([CH:26]=[CH:27][CH:28]=1)[C:23]([NH:1][C:2]1[N:7]=[C:6]2[C:8]([CH:11]3[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]3)=[CH:9][NH:10][C:5]2=[CH:4][CH:3]=1)=[O:24])#[N:19] | CN1CCC(c2c[nH]c3ccc(N)nc23)CC1 | N#Cc1cccc(C(=O)Cl)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Beginning with 0.015 gm (0.065 mMol) 5-amino-3-(1-methylpiperidin-4-yl)pyrrolo[3,2-b]pyridine and 0.012 gm (0.072 mMol) 3-cyanobenzoyl chloride, 0.021 gm (92%) of the title compound were prepared essentially by the procedure described in Example 7. | CN1CCC(c2c[nH]c3ccc(NC(=O)c4cccc(C#N)c4)nc23)CC1 | null | 89.9 | null |
971,411 | ord_dataset-03ba810b7f464a06b5d8787af2e8b64e | null | 2010-01-01T00:06:00 | true | [Cl:1][C:2]1[C:22]([O:23][CH3:24])=[CH:21][CH:20]=[CH:19][C:3]=1[O:4][C:5]1[CH2:9][N:8]([C@@H:10]([CH2:14][CH:15]([CH3:17])[CH3:16])[C:11]([OH:13])=O)[C:7](=[O:18])[CH:6]=1.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[NH2:46][C:47]1[CH:51]=[CH:50][N:49]([CH2:52][C:53]([CH3:56])([OH:55])[CH3:54])[N:48]=1>ClCCl>[OH:55][C:53]([CH3:56])([CH3:54])[CH2:52][N:49]1[CH:50]=[CH:51][C:47]([NH:46][C:11](=[O:13])[C@@H:10]([N:8]2[CH2:9][C:5]([O:4][C:3]3[CH:19]=[CH:20][CH:21]=[C:22]([O:23][CH3:24])[C:2]=3[Cl:1])=[CH:6][C:7]2=[O:18])[CH2:14][CH:15]([CH3:17])[CH3:16])=[N:48]1 | COc1cccc(OC2=CC(=O)N([C@@H](CC(C)C)C(=O)O)C2)c1Cl | CC(C)(O)Cn1ccc(N)n1 | null | CCN=C=NCCCN(C)C | On1nnc2ccccc21 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | 25 | 2 | A solution of (S)-2-[4-(2-chloro-3-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid (200 mg, 0.57 mmol) in dichloromethane (10 mL) was treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (96 mg, 0.62 mmol) and 1-hydroxybenzotriazole (80 mg, 0.60 mmol). The reaction mixture was stirred at 25° C. for 2 h followed by the addition of 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in U.S. Pat. Appl. US2008021032 Example 80, 105 mg, 0.68 mmol). The reaction mixture was stirred for 18 h at 25° C., under nitrogen. The reaction mixture was diluted with dichloromethane, washed with 2N aqueous hydrochloric acid, saturated sodium bicarbonate solution, a saturated sodium chloride solution and dried over magnesium sulfate. The organic layer was concentrated, and the crude product was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 12 g; 0% to 100% ethyl acetate/hexanes) to afford (S)-2-[4-(2-Chloro-3-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-amide (198 mg, 71%) as an off-white solid: LR-ES-MS m/z calculated for C24H31ClN4O5 [M]− 490, observed [M+H]+ 491; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.90 (d, J=6.6 Hz, 3H), 0.93 (d, J=6.6 Hz, 3H), 1.05 (s, 3H), 1.06 (s, 3H), 1.43 (br. s., 1H), 1.48-1.65 (m, 1H), 1.68-1.84 (m, 1H), 3.89 (br. s., 2H), 3.90 (s, 3H), 4.19 (d, J=18.6 Hz, 1H), 4.60 (d, J=18.6 Hz, 1H), 4.68 (s, 1H), 4.80 (s, 1H), 4.89 (dd, J=10.9, 4.8 Hz, 1H), 6.44 (d, J=2.1 Hz, 1H), 7.09 (dd, J=8.5, 1.3 Hz, 1H), 7.13 (dd, J=8.5, 1.3 Hz, 1H), 7.41 (t, J=8.5 Hz, 1H), 7.54 (d, J=2.1 Hz, 1H), 10.81 (s, 1H). | COc1cccc(OC2=CC(=O)N([C@@H](CC(C)C)C(=O)Nc3ccn(CC(C)(C)O)n3)C2)c1Cl | null | 70.8 | null |
807,187 | ord_dataset-da49b0378abf41bf92ab8ecdd3feb28b | null | 2008-01-01T00:02:00 | true | [Cl:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[C:22]([OH:24])=O)[C:5]([NH:7][CH2:8][C:9]1[NH:13][C:12]2[CH:14]=[CH:15][C:16]([Cl:18])=[CH:17][C:11]=2[N:10]=1)=[O:6].[N:25]1([CH2:30][CH:31]2[CH2:36][CH2:35][CH2:34][NH:33][CH2:32]2)[CH2:29][CH2:28][CH2:27][CH2:26]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)CC)C>CS(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[C:22]([N:33]1[CH2:34][CH2:35][CH2:36][CH:31]([CH2:30][N:25]2[CH2:26][CH2:27][CH2:28][CH2:29]2)[CH2:32]1)=[O:24])[C:5]([NH:7][CH2:8][C:9]1[NH:13][C:12]2[CH:14]=[CH:15][C:16]([Cl:18])=[CH:17][C:11]=2[N:10]=1)=[O:6] | O=C(NCc1nc2cc(Cl)ccc2[nH]1)c1ccc(C(=O)O)c(Cl)c1 | C1CNCC(CN2CCCC2)C1 | null | CN(C)C(On1nnc2ccccc21)=[N+](C)C | F[B-](F)(F)F | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(CC)CC | CS(C)=O | null | null | null | null | null | null | null | null | null | null | null | Prepared analogously to Example 1d from 3-chloro-N-(5-chloro-1H-benzimidazol-2-ylmethyl)-4-carboxybenzamide, 3-(pyrrolidin-1-ylmethyl)piperidine, TBTU, and triethylamine in DMSO at ambient temperature. HPLC-MS results: retention time: 3.05 minutes; C26H29Cl2N5O2 (514.45); mass spectrum: (M+H)+=514.2. | O=C(NCc1nc2cc(Cl)ccc2[nH]1)c1ccc(C(=O)N2CCCC(CN3CCCC3)C2)c(Cl)c1 | null | null | null |
1,418,445 | ord_dataset-f8e6e6a2d2bf4135b9e346456c81700f | null | 2014-01-01T00:04:00 | true | [C:1]1([CH3:18])[CH:6]=[CH:5][C:4]([S:7]([N:10]2[CH:14]=[CH:13][C:12]([C:15]([OH:17])=O)=[CH:11]2)(=[O:9])=[O:8])=[CH:3][CH:2]=1.N=C=N.Cl.Cl.[NH:24]1[C:28]2([CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)[CH2:27][NH:26]/[C:25]/1=[N:34]\[C:35]([C:37]1[C:42]([NH2:43])=[N:41][C:40]([NH2:44])=[C:39]([Cl:45])[N:38]=1)=[O:36].CN1CCOCC1>CN1C(=O)CCC1>[C:1]1([CH3:18])[CH:2]=[CH:3][C:4]([S:7]([N:10]2[CH:14]=[CH:13][C:12]([C:15]([N:31]3[CH2:32][CH2:33][C:28]4([NH:24]/[C:25](=[N:34]/[C:35]([C:37]5[C:42]([NH2:43])=[N:41][C:40]([NH2:44])=[C:39]([Cl:45])[N:38]=5)=[O:36])/[NH:26][CH2:27]4)[CH2:29][CH2:30]3)=[O:17])=[CH:11]2)(=[O:8])=[O:9])=[CH:5][CH:6]=1 | Nc1nc(N)c(C(=O)/N=C2\NCC3(CCNCC3)N2)nc1Cl | Cc1ccc(S(=O)(=O)n2ccc(C(=O)O)c2)cc1 | null | Cl | N=C=N | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN1CCCC1=O | CN1CCOCC1 | null | null | null | null | null | null | null | null | null | 25 | null | A solution of 1-(Toluene-4-sulfonyl)-1H-pyrrole-3-carboxylic acid (0.023 g, 0.085 mmol) in NMP (850 l) is added to PS-carbodiimide (190 mg of 1.3 mmol/g loading, 0.24 mmol), followed by a solution of 3,5-Diamino-6-chloro-pyrazine-2-carboxylic acid [1,3,8-triaza-spiro[4.5]dec-(2E)-ylidene]-amide dihydrochloride (Ex. 38) (0.08 mmol) and N-methyl morpholine (8 l, 0.08 mmol) in NMP (1 ml), and the resulting reaction mixture is shaken at room temperature. The reaction mixture is filtered and the resin is washed with NMP (1 ml). The collected filtrate is concentrated in vacuo and the residues are purified by mass-directed preparative HPLC. The purified fractions are evaporated under vacuum to afford the title compound; [M+H]+ 572.08 | Cc1ccc(S(=O)(=O)n2ccc(C(=O)N3CCC4(CC3)CN/C(=N\C(=O)c3nc(Cl)c(N)nc3N)N4)c2)cc1 | null | null | null |
155,187 | ord_dataset-d1c545e3afc447099315419421478aab | null | 1987-01-01T00:03:00 | true | [C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[S:24][C:14]3=[N:15][C:16](Cl)=[C:17]([N+:20]([O-:22])=[O:21])[C:18](=[O:19])[N:13]3[N:12]=2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH3:25]>C(O)C.CN(C)C=O>[NH2:25][C:16]1[N:15]=[C:14]2[S:24][C:11]([C:8]3[CH:9]=[CH:10][C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])=[CH:6][CH:7]=3)=[N:12][N:13]2[C:18](=[O:19])[C:17]=1[N+:20]([O-:22])=[O:21] | CC(C)(C)c1ccc(-c2nn3c(=O)c([N+](=O)[O-])c(Cl)nc3s2)cc1 | N | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | null | 1.9 g of 2-(4-tert-butylphenyl)-7-chloro-6-nitro-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one was suspended in a mixture of 20 ml of ethanol and 10 ml of dimethylformamide, and 5 ml of concentrated aqueous ammonia was added dropwise to the suspension while maintaining at a temperature of 60° C. to 70° C. After heating at that temperature for 2 hours, the mixture was cooled and the precipitate formed was separated by filtration to obtain 1.3 g of 7-amino-2-(4-tert-butylphenyl)-6-nitro-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one as pale yellow prisms having a melting point higher than 300° C. | CC(C)(C)c1ccc(-c2nn3c(=O)c([N+](=O)[O-])c(N)nc3s2)cc1 | null | null | null |
1,227,428 | ord_dataset-cde802cdb7434a5f82a22981ccaefc4e | null | 2012-01-01T00:11:00 | true | [OH:1][CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[O:12][C:13]3[C:18]([C:19](=[O:25])[C:20]=2[O:21][CH2:22][O:23][CH3:24])=[CH:17][CH:16]=[C:15]([O:26][CH2:27][O:28][CH3:29])[CH:14]=3)=[CH:7][C:6]=1[O:30][CH2:31][O:32][CH3:33].CCN(C(C)C)C(C)C.[CH3:43][C:44]1[CH:49]=[CH:48][C:47]([S:50](Cl)(=[O:52])=[O:51])=[CH:46][CH:45]=1>CCOCC>[CH3:43][C:44]1[CH:49]=[CH:48][C:47]([S:50]([O:1][CH2:2][CH2:3][O:4][C:5]2[CH:10]=[CH:9][C:8]([C:11]3[O:12][C:13]4[C:18]([C:19](=[O:25])[C:20]=3[O:21][CH2:22][O:23][CH3:24])=[CH:17][CH:16]=[C:15]([O:26][CH2:27][O:28][CH3:29])[CH:14]=4)=[CH:7][C:6]=2[O:30][CH2:31][O:32][CH3:33])(=[O:52])=[O:51])=[CH:46][CH:45]=1 | Cc1ccc(S(=O)(=O)Cl)cc1 | COCOc1ccc2c(=O)c(OCOC)c(-c3ccc(OCCO)c(OCOC)c3)oc2c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(C(C)C)C(C)C | CCOCC | null | null | null | null | null | null | null | null | null | 25 | 15 | To 2-(4-(2-hydroxyethoxy)-3-(methoxymethoxy)phenyl)-3,7-bis(methoxymethoxy)-4H-chromen-4-one (18 mg, 0.039 mmol) and DIPEA (15 mg, 0.11 mmol) was added 4-methylbenzene-1-sulfonyl chloride (11 mg, 0.058 mmol). The mixture was stirred at rt for 15 h under Ar atmosphere and diluted with ether (30 mL). It was washed with 0.5 M HCl(2×30 mL) and water (50 mL), and dried over MgSO4 and concentrated. The crude product was chromatographed to afford 2-(4-(3,7-bis(methoxymethoxy)-4-oxo-4H-chromen-2-yl)-2-(methoxymethoxy)phenoxy)ethyl 4-methylbenzenesulfonate (AD-C-001P-WZ01079) as a yellow wax (20 mg, 83%). 1H NMR (400 MHz, CDCl3) δ 8.15 (dd, J=8.8, 2.0 Hz, 1H), 7.89 (d, J=2.0 Hz, 1H), 7.76 (dd, J=8.4 Hz, 2.0 Hz, 2H), 7.73 (dd, J=8.4, 2.0 Hz, 1H), 7.36 (d, J=6.8 Hz, 2H), 7.27 (d, J=2.0 Hz, 1H), 7.14 (d, J=2.4 Hz, 1H), 7.05 (dd, J=8.8, 2.0 Hz, 1H), 6.94 (dd, J=8.8, 2.0 Hz, 1H), 5.29 (d, J=1.6 Hz, 2H), 5.22 (d, J=2.0 Hz, 4H), 4.42 (t, J=3.0 Hz, 2H), 4.32 (t, J=3.0 Hz, 2H), 3.53 (d, J=2.4 Hz, 3H), 3.52 (d, J=2.0 Hz, 3H), 3.20 (d, J=2.4 Hz, 3H), 2.46 (s, 3H); MS (ESI) m/z 617 (M+H+). | COCOc1ccc2c(=O)c(OCOC)c(-c3ccc(OCCOS(=O)(=O)c4ccc(C)cc4)c(OCOC)c3)oc2c1 | null | null | null |
1,592,196 | ord_dataset-e8c6a25568b64529b960953990e6921f | null | 2015-01-01T00:06:00 | true | [NH2:1][C:2]1[C:3]([C:10](/[N:12]=[C:13]2/[NH:14][C:15]3([CH2:22][CH2:21][N:20]([C:23]([C:25]4[CH:26]=[C:27]([S:31]([NH:34][CH2:35][CH2:36][C:37]([OH:39])=[O:38])(=[O:33])=[O:32])[CH:28]=[CH:29][CH:30]=4)=[O:24])[CH2:19][CH2:18]3)[CH2:16][NH:17]/2)=[O:11])=[N:4][C:5]([Cl:9])=[C:6]([NH2:8])[N:7]=1.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.O[CH2:74][C:75]([N:77]1[CH2:81][CH2:80][CH2:79][CH:78]1[C:82]([F:85])([F:84])[F:83])=[O:76]>CN(C=O)C>[O:76]=[C:75]([N:77]1[CH2:81][CH2:80][CH2:79][CH:78]1[C:82]([F:85])([F:83])[F:84])[CH2:74][O:38][C:37](=[O:39])[CH2:36][CH2:35][NH:34][S:31]([C:27]1[CH:28]=[CH:29][CH:30]=[C:25]([C:23]([N:20]2[CH2:21][CH2:22][C:15]3([NH:14]/[C:13](=[N:12]/[C:10]([C:3]4[C:2]([NH2:1])=[N:7][C:6]([NH2:8])=[C:5]([Cl:9])[N:4]=4)=[O:11])/[NH:17][CH2:16]3)[CH2:18][CH2:19]2)=[O:24])[CH:26]=1)(=[O:32])=[O:33] | O=C(CO)N1CCCC1C(F)(F)F | Nc1nc(N)c(C(=O)/N=C2\NCC3(CCN(C(=O)c4cccc(S(=O)(=O)NCCC(=O)O)c4)CC3)N2)nc1Cl | null | CN(C)C(On1nnc2cccnc21)=[N+](C)C | F[P-](F)(F)(F)(F)F | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(C(C)C)C(C)C | CN(C)C=O | null | null | null | null | null | null | null | null | null | 25 | 0.25 | To a stirred solution of 3-(3-{2-[(E)-3,5-Diamino-6-chloro-pyrazine-2-carbonylimino]-1,3,8-triaza-spiro[4.5]decane-8-carbonyl}-benzenesulfonylamino)-propionic acid (step 2) (400 mg, 0.690 mmol) and N,N-diisopropylethylamine (357 mg, 2.76 mmol) in DMF (4 ml) was added HATU (262 mg, 0.690 mmol). The solution was stirred at RT for 15 min, after which time 2-hydroxy-1-(2-(trifluoromethyl)pyrrolidin-1-yl)ethanone (Int. D) (262 mg, 0.690 mmol) in DMF (2 ml) was added. The resulting solution was stirred at RT for 6 days, after which time it was poured onto water (10 ml). A white precipitate formed which was collected by filtration, and washed with iso-hexane (20 ml), and purified by C18 reverse phase chromatography eluting with MeCN/water/0.1% TFA to afford the title product; 1H NMR (400 MHz, DMSO-d6) δ 11.03 (1H, s), 9.37 (1H, s), 9.02 (1H, s), 7.92-7.29 (4H, m), 7.24 (14N, s) 7.12 (14N,s), 6.96 (14N,s), 4.95-3.90 (11H, m), 3.66 (2H, t), 3.41 (2H, t), 3.35 (2H, m), 3.07 (2H, t) 2.20-1.61 (7H, m); LC-MS Rt 0.91 mins; 759.0 [M+H]+, Method 2minLC_v003. | Nc1nc(N)c(C(=O)/N=C2\NCC3(CCN(C(=O)c4cccc(S(=O)(=O)NCCC(=O)OCC(=O)N5CCCC5C(F)(F)F)c4)CC3)N2)nc1Cl | null | null | null |
1,465,188 | ord_dataset-fd1fa959d6264608b0b7fcda16741bfd | null | 2014-01-01T00:08:00 | true | [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8]([C@H:11]1[CH2:15][NH:14][C@H:13]([C:16]([NH:18][C:19]2([C:22]#[N:23])[CH2:21][CH2:20]2)=[O:17])[CH2:12]1)(=[O:10])=[O:9].[S:24]1[CH2:29][CH2:28][CH:27]([N:30]2[CH2:33][CH2:32][CH:31]2[C:34]([O-])=[O:35])[CH2:26][CH2:25]1.[Li+]>>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8]([C@H:11]1[CH2:15][N:14]([C:34]([CH:31]2[CH2:32][CH2:33][N:30]2[CH:27]2[CH2:26][CH2:25][S:24][CH2:29][CH2:28]2)=[O:35])[C@H:13]([C:16]([NH:18][C:19]2([C:22]#[N:23])[CH2:21][CH2:20]2)=[O:17])[CH2:12]1)(=[O:10])=[O:9] | N#CC1(NC(=O)[C@@H]2C[C@@H](S(=O)(=O)c3ccccc3Cl)CN2)CC1 | O=C([O-])C1CCN1C1CCSCC1 | null | [Li+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The reaction of (2S,4R)-4-(2-chlorophenylsulfonyl)-N-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide 7H and lithium 1-(tetrahydro-2H-thiopyran-4-yl)azetidine-2-carboxylate 20J carried out according to the general procedure L yielded (2S,4R)-4-(2-chlorophenylsulfonyl)-N-(1-cyanocyclopropyl)-1-(1-(tetrahydro-2H-thiopyran-4-yl)azetidine-2-carbonyl)pyrrolidine-2-carboxamide 1:1 epimers as a light brown solid (quant.). MS ISP (m/e): 537.3 (100) [(M+H)]]+. | N#CC1(NC(=O)[C@@H]2C[C@@H](S(=O)(=O)c3ccccc3Cl)CN2C(=O)C2CCN2C2CCSCC2)CC1 | null | null | null |
1,495,729 | ord_dataset-366bdd9ee72d474cbe6f3f9e54dd96d2 | null | 2014-01-01T00:10:00 | true | [OH:1][C:2]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[CH:6][C:3]=1[CH:4]=[O:5].C([O-])(=O)C.[Na+].[Br:17]Br.S([O-])([O-])(=O)=S.[Na+].[Na+]>C(O)(=O)C>[Br:17][C:9]1[C:2]([OH:1])=[C:3]([CH:6]=[C:7]([O:10][CH3:11])[CH:8]=1)[CH:4]=[O:5] | BrBr | COc1ccc(O)c(C=O)c1 | null | CC(=O)[O-] | O=S([O-])([O-])=S | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(=O)O | null | null | null | null | null | null | null | null | null | null | 25 | 2 | To 2-hydroxy-5-methoxybenzaldehyde (4.1 mL, 32.86 mmol) in acetic acid (150 mL) were added sodium acetate (4.0 g, 49.3 mmol) and bromine (2.2 mL, 42.7 mmol) and the mixture was stirred at rt for 2 h. Aqueous sodium thiosulfate was added and the mixture was concentrated by rotary evaporation. The solid was dissolved in dichloromethane and washed with water. The organic phase was separated, dried over MgSO4, filtered and the solvent removed by rotary evaporation. The solid residue was recrystallized from ethanol to yield 3-bromo-2-hydroxy-5-methoxybenzaldehyde (4.55 g, 60%). | COc1cc(Br)c(O)c(C=O)c1 | null | 59.9 | null |
358,479 | ord_dataset-58ec5adfcd8648dc9e26ee757d289517 | null | 1997-01-01T00:03:00 | true | [ClH:1].C([O:9][C:10]1[CH:15]=[CH:14][C:13]([CH:16]([OH:24])[CH2:17][O:18][CH2:19][CH2:20][N:21]([CH3:23])[CH3:22])=[CH:12][CH:11]=1)C1C=CC=CC=1>[C].[Pd].CO>[ClH:1].[OH:9][C:10]1[CH:11]=[CH:12][C:13]([CH:16]([OH:24])[CH2:17][O:18][CH2:19][CH2:20][N:21]([CH3:22])[CH3:23])=[CH:14][CH:15]=1 | CN(C)CCOCC(O)c1ccc(OCc2ccccc2)cc1 | null | null | [Pd] | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | null | 2 | A mixture of 2.0 g of 1-(4-benzyloxyphenyl)-2-[2-(N,N-dimethylamino)ethoxy]ethanol hydrochloride, 500 mg of 10% palladium-carbon and 10 ml of methanol was subjected to hydrogenation for 2 hours at room temperature under atmospheric pressure. After the completion of the reaction, palladium-carbon was removed by filtration. The solvent was removed by distillation under reduced pressure to obtain 1.4 g of 1-(4-hydroxyphenyl)-2-[2-(N,N-dimethylamino)ethoxy]ethanol hydrochloride (Compound No. 170). | CN(C)CCOCC(O)c1ccc(O)cc1 | null | 94.1 | null |
904,764 | ord_dataset-46d216f2c4374ef5b9df90427e2a4cd4 | null | 2009-01-01T00:09:00 | true | C([N:8]1[CH2:13][CH2:12][C:11]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[F:22])([OH:14])[CH2:10][CH2:9]1)C1C=CC=CC=1>C(OCC)(=O)C.[Pd]>[F:22][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[CH2:15][C:11]1([OH:14])[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]1 | OC1(Cc2ccccc2F)CCN(Cc2ccccc2)CC1 | null | null | [Pd] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOC(C)=O | null | null | null | null | null | null | null | null | null | null | null | null | A solution of EXAMPLE 1A (39.0 g, 131 mmol) in ethyl acetate (500 mL) was treated with Pd/C (3.90 g), stirred under hydrogen atmosphere (60 psi) until the reaction was complete by TLC analysis, and filtered. The filtrate was concentrated to give a residue that was used without further purification. MS (ESI) m/e 210 (M+H)+. | OC1(Cc2ccccc2F)CCNCC1 | null | null | null |
322,631 | ord_dataset-24ad29d930104afea313b6c3bd11099e | null | 1996-01-01T00:01:00 | true | [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:17]([CH2:30][C:31]([O:33][CH3:34])=[O:32])[S:18]([C:21]2[CH:26]=[CH:25][C:24]([N+:27]([O-])=O)=[CH:23][CH:22]=2)(=[O:20])=[O:19])=[C:6]([CH:16]=1)[C:7]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[F:15])=[O:8].CO>C(OCC)(=O)C.[Pd]>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:17]([CH2:30][C:31]([O:33][CH3:34])=[O:32])[S:18]([C:21]2[CH:26]=[CH:25][C:24]([NH2:27])=[CH:23][CH:22]=2)(=[O:19])=[O:20])=[C:6]([CH:16]=1)[C:7]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[F:15])=[O:8] | COC(=O)CN(c1ccc(Cl)cc1C(=O)c1ccccc1F)S(=O)(=O)c1ccc([N+](=O)[O-])cc1 | null | null | [Pd] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | CCOC(C)=O | null | null | null | null | null | null | null | null | null | null | null | The 5-chloro-2'-fluoro-2-[N-(methoxycarbonyl-methyl)-N-(4-nitrophenylsulfonyl)amino]benzophenone prepared in Example 2, step b, is dissolved in 100 ml of ethyl acetate and 5 ml of methanol and hydrogenated at ordinary pressure for 2 hours in the presence of 620 mg of 10% palladium-on-charcoal; the existence of 3 compounds (starting material, intermediate and expected product) is observed in TLC. The catalyst is filtered off, the solvent is evaporated off and the residue is chromatographed on silica gel. The expected compound is eluted with DCM containing 1% of methanol. After recrystallization from DCM/isopropyl ether, m.p.=168°-170° C. | COC(=O)CN(c1ccc(Cl)cc1C(=O)c1ccccc1F)S(=O)(=O)c1ccc(N)cc1 | null | null | null |
1,330,879 | ord_dataset-cfad8b3f00044bcda60a96b019f09872 | null | 2013-01-01T00:08:00 | true | [N:1]([C@@H:4]1[C:9]([F:11])([F:10])[CH2:8][CH2:7][CH2:6][C@H:5]1[NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[N+]=[N-]>CO>[NH2:1][C@@H:4]1[C:9]([F:11])([F:10])[CH2:8][CH2:7][CH2:6][C@H:5]1[NH:12][C:13](=[O:19])[O:14][C:15]([CH3:17])([CH3:16])[CH3:18] | CC(C)(C)OC(=O)N[C@@H]1CCCC(F)(F)[C@H]1N=[N+]=[N-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | null | 48 | To a clean dry 1 L RBF charged with tert-butyl [(1R,2S)-2-azido-3,3-difluorocyclohexyl]carbamate 27 (18.84 g, 68.2 mmol) was added 400 mL methanol. The system was degassed and purged (3× with N2) before the addition of Pd/C (1.45 g). The reaction was stirred for 2 d under 1 atm of hydrogen. Upon reaction completion, the reaction was filtered through a plug of celite and concentrated to dryness to yield tert-butyl [(1R,2S)-2-amino-3,3-difluorocyclohexyl]carbamate 30 (16.47 g, 97% yield) as a pure white solid. 1H NMR (CDCl3, 500 MHz) 4.76-4.74 (1H, d, J=10 Hz), 3.61-3.56 (1H, m), 2.63-2.59 (1H, dd 0.1-9.5 Hz), 2.2-2.0 (2H, m), 1.8-1.68, (2H, m), 1.53-1.42 (11H, m), 1.29-1.21 (m, 2H); 19F NMR (CDCl3, 564 MHz) −101.7-−102.1 (1F, J=241 Hz), −114.3-−114.9 (1F, m) | CC(C)(C)OC(=O)N[C@@H]1CCCC(F)(F)[C@H]1N | null | 96.5 | null |
1,223,866 | ord_dataset-cde802cdb7434a5f82a22981ccaefc4e | null | 2012-01-01T00:11:00 | true | [C:1](N1C=CC=CC1=O)(N1C=CC=CC1=O)=[S:2].[Br:17][C:18]1[CH:19]=[C:20]2[C:25](=[CH:26][CH:27]=1)[CH:24]=[N:23][C:22]([NH2:28])=[CH:21]2>ClCCl>[Br:17][C:18]1[CH:19]=[C:20]2[C:25](=[CH:26][CH:27]=1)[CH:24]=[N:23][C:22]([N:28]=[C:1]=[S:2])=[CH:21]2 | O=c1ccccn1C(=S)n1ccccc1=O | Nc1cc2cc(Br)ccc2cn1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | 25 | 3 | To a solution of 1,1′-thiocarbonyldipyridin-2(1H)-one (0.251 g, 1.080 mmol) in dichloromethane at room temperature was added 6-bromoisoquinolin-3-amine (0.241 g, 1.080 mmol). The solution was stirred at room temperature for 3 hours. LC/MS indicated formation of the desired product. The deep orange solution was purified by silica gel chromatography (0-10% ethyl acetate-hexanes) to afford: 6-bromo-3-isothiocyanatoisoquinoline (0.1 g, 0.377 mmol, 35% yield) as a yellow oil. R.T.=2.54; [M+H]+=267.04. | S=C=Nc1cc2cc(Br)ccc2cn1 | null | null | null |
233,896 | ord_dataset-45d20d09e4d64f45bdd419044025b4d3 | null | 1991-01-01T00:09:00 | true | [CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:18]=[CH:19][C:20]2[N:21]=[C:22]3[CH:27]=[C:26]([CH3:28])[CH:25]=[CH:24][N:23]3[CH:29]=2)[CH:12]=[CH:13][C:14]=1[N+:15]([O-:17])=[O:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P(Cl)(Cl)(Cl)=O.CN(C)[CH:37]=[O:38]>>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:18]=[CH:19][C:20]2[N:21]=[C:22]3[CH:27]=[C:26]([CH3:28])[CH:25]=[CH:24][N:23]3[C:29]=2[CH:37]=[O:38])[CH:12]=[CH:13][C:14]=1[N+:15]([O-:17])=[O:16])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1 | CN(C)C=O | Cc1ccn2cc(C=Cc3ccc([N+](=O)[O-])c(OCc4ccccc4)c3)nc2c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O=P(Cl)(Cl)Cl | null | null | null | null | null | null | null | null | null | null | null | null | A solution of 2-[2-(3-benzyloxy-4-nitrophenyl)vinyl]-7-methylimidazo[1,2-a]pyridine (9.00 g) in N,N-dimethylformamide (50 ml), was added dropwise to a solution of phosphorus oxychloride (6.36 ml) in N,N-dimethylformamide (90 ml) at ambient temperature with stirring. After the mixture was stirred for 6 hours, the solvent was evaporated in vacuo. The residue was mixed with water (200 ml) and dichloromethane (300 ml) and made basic with aqueous potassium carbonate. The resulting precipitate was collected, washed with water and recrystallized from a mixture of methanol, chloroform and dioxane to give 2-[2-(3-benzyloxy-4-nitrophenyl)vinyl]-3-formyl-7-methylimidazo[1,2-a]pyridine (5.15 g). | Cc1ccn2c(C=O)c(C=Cc3ccc([N+](=O)[O-])c(OCc4ccccc4)c3)nc2c1 | null | null | null |
1,205,157 | ord_dataset-fb72428f30234761b4216139dc228d0c | null | 2012-01-01T00:09:00 | true | [N:1]1[CH:6]=[CH:5][C:4]([C:7](=[N:10][OH:11])[CH2:8][CH3:9])=[CH:3][CH:2]=1.[Li+].CC([N-]C(C)C)C.[C:20]([O:27][CH2:28][CH3:29])(=[O:26])[C:21]([O:23]CC)=O>C1COCC1>[OH:11][N:10]=[C:7]([C:4]1[CH:3]=[CH:2][N:1]=[CH:6][CH:5]=1)[CH:8]([CH3:9])[C:21](=[O:23])[C:20]([O:27][CH2:28][CH3:29])=[O:26] | CCC(=NO)c1ccncc1 | CCOC(=O)C(=O)OCC | null | CC(C)[N-]C(C)C | [Li+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | 0 | 1.5 | 1-(Pyridin-4-yl)propan-1-one oxime (5.3 g, 35.3 mmol) was dissolved in 120 mL of THF and cooled to 0° C. LDA solution (41 mL, 81.3 mmol, 2M in heptane/THF/ethyl benzene) was added dropwise, and the reaction mixture was stirred at 0° C. for 1.5 hour and then warmed to room temperature. The mixture was then transferred to a syringe and added dropwise to a flask containing a pre-cooled mixture of diethyl oxalate (24 mL, 177 mmol) and THF (100 mL) at 0° C. After the addition was complete, the reaction mixture was stirred at room temperature for 18 hours. The mixture was cooled in an ice bath and quenched with 150 mL of 10% hydrochloric acid. EtOAc (150 mL) was added and solid NaHCO3 was added with vigorous stirring the aqueous layer was basic (pH>8). The aqueous layer was extracted with additional EtOAc and the combined organic layer was dried over MgSO4 and concentrated. The crude product was purified by chromatography (10-60% EtOAc/hexanes) to give 5.3 g of the title compound. MS: (+) m/z 251.43 (M+1). | CCOC(=O)C(=O)C(C)C(=NO)c1ccncc1 | null | 60 | null |
1,354,393 | ord_dataset-6034127657614f02860ed057b62b882e | null | 2013-01-01T00:10:00 | true | COC1C=CC(C[N:8]2[C:16]3[CH:15]=[CH:14][N:13]=[C:12]([NH:17][CH:18]4[CH2:23][CH2:22][O:21][CH2:20][CH2:19]4)[C:11]=3[C:10]([O:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[N:9]2)=CC=1.FC(F)(F)S(O)(=O)=O>C(Cl)Cl>[O:24]([C:10]1[C:11]2[C:12]([NH:17][CH:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[N:13][CH:14]=[CH:15][C:16]=2[NH:8][N:9]=1)[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1 | COc1ccc(Cn2nc(Oc3ccccc3)c3c(NC4CCOCC4)nccc32)cc1 | null | null | O=S(=O)(O)C(F)(F)F | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | 25 | 2 | The crude 1-(4-methoxybenzyl)-3-phenoxy-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]pyridin-4-amine from step 1 was added to methylene chloride (5 mL) and trifluoromethanesulfonic acid (0.5 mL), and the resulting mixture was stirred at room temperature for two hours. The mixture was concentrated under reduced pressure and the residue was purified by reverse phase HPLC to give 3-phenoxy-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]pyridin-4-amine: LC-MS (Method G): m/z=311.1; 1H NMR (400 MHz, DMSO): δ 12.43 (s, 1H), 7.73 (d, J=6.1, 1H), 7.42 (t, J=7.9, 2H), 7.26 (d, J=8.0, 2H), 7.19 (t, J=7.3, 1H), 6.60 (d, J=6.1, 1H), 5.43 (d, J=7.7, 1H), 4.19 (m, 1H), 3.79 (d, J=11.6, 2H, 1.83 (d, J=12.4, 2H), 1.43 (m, 2H). | c1ccc(Oc2n[nH]c3ccnc(NC4CCOCC4)c23)cc1 | null | null | null |
842,743 | ord_dataset-e2b35e721c2741999b0005d12691f9fe | null | 2008-01-01T00:10:00 | true | [CH2:1]([C:5]1([CH2:19][CH2:20][CH2:21][CH:22]=[CH2:23])[CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:14][CH2:15][O:16][CH3:17])[CH:11]=2)[C:6]1=[O:18])[CH2:2][CH2:3][CH3:4].[CH2:24]([Mg]Br)[CH:25]=[CH2:26]>O1CCCC1>[CH2:1]([C:5]1([CH2:19][CH2:20][CH2:21][CH:22]=[CH2:23])[CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:14][CH2:15][O:16][CH3:17])[CH:11]=2)[C:6]1([C:25]([CH3:26])=[CH2:24])[OH:18])[CH2:2][CH2:3][CH3:4] | C=CC[Mg]Br | C=CCCCC1(CCCC)Cc2cc(OCOC)ccc2C1=O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | 25 | null | A solution of 2-butyl-5-(methoxymethoxy)-2-(4-pentenyl)-1-indanone (400 mg, 1.27 mmol) in anhydrous tetrahydrofuran (THF, 5 mL) was placed under a N2 atmosphere, cooled in a dry ice-acetone bath, stirred, and treated with 2-propenyl magnesium bromide, (1M in THF, 1.9 mL, 1.9 mmol). After warming to room temperature, the mixture was treated with additional 2-propenyl magnesium bromide (1M in THF, 6 mL, 6 mmol) and stirred at room temperature overnight. The mixture was quenched with saturated aqueous NH4Cl, dried over MgSO4, filtered through a pad of silica, and concentrated under vacuum to afford an oil. The crude product was purified by Biotage™ (Charlottesville, Va.) flash chromatography on a 40S (4.0×7.0 cm) silica gel column, eluting with 19:1 hexanes-EtOAc. The product-containing fractions were evaporated under vacuum to afford 2-butyl-1-isopropenyl-5-(methoxymethoxy)-2-(4-pentenyl)-1-indanol as an oil. | C=CCCCC1(CCCC)Cc2cc(OCOC)ccc2C1(O)C(=C)C | null | null | null |
1,597,765 | ord_dataset-e8c6a25568b64529b960953990e6921f | null | 2015-01-01T00:06:00 | true | [NH2:1][C:2]1[C:3]2[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:13][CH:12]=3)=[C:9](F)[N:8]([C@@H:25]3[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26]3)[C:4]=2[N:5]=[CH:6][N:7]=1.[CH3:37][O:38][Na]>CO>[NH2:1][C:2]1[C:3]2[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:13][CH:12]=3)=[C:9]([O:38][CH3:37])[N:8]([C@@H:25]3[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26]3)[C:4]=2[N:5]=[CH:6][N:7]=1 | CO[Na] | CC(C)(C)OC(=O)N1CC[C@@H](n2c(F)c(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | null | null | To a solution of (R)-tert-butyl 3-(4-amino-6-fluoro-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate (3) (250 mg, 0.51 mmol) in MeOH was added MeONa. The resulting mixture was heated to reflux under N2 overnight. After cooling down to r. t., the reaction mixture was concentrated and the residue was partitioned between DCM and water. The layers were separated. The organic phase was washed with brine, dried over Na2SO4 and concentrated under reduced pressure to give (R)-tert-butyl 3-(4-amino-6-methoxy-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate (87) (230 mg, 90% yield) as a yellow solid. LC-MS (ESI): m/z (M+1) 502.1. | COc1c(-c2ccc(Oc3ccccc3)cc2)c2c(N)ncnc2n1[C@@H]1CCN(C(=O)OC(C)(C)C)C1 | null | 90 | null |
1,586,795 | ord_dataset-380e279f82154dba9e08ab51b3bdd08a | null | 2015-01-01T00:05:00 | true | [Cl:1][C:2]1[N:7]=[C:6]([S:8][C:9]2[CH:10]=[C:11]([NH2:15])[CH:12]=[CH:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1.[C:16](O)(=[O:19])[CH:17]=[CH2:18]>>[Cl:1][C:2]1[N:7]=[C:6]([S:8][C:9]2[CH:10]=[C:11]([NH:15][C:16](=[O:19])[CH:17]=[CH2:18])[CH:12]=[CH:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1 | C=CC(=O)O | Nc1cccc(Sc2ccnc(Cl)n2)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | In a procedure analogous to Example 15, reaction of 3-(2-chloropyrimidin-4-ylthio)benzenamine (300 mg, 1.26 mmol) and acrylic acid (173 μL, 2.52 mmol) furnished the product (250 mg, 68%). | C=CC(=O)Nc1cccc(Sc2ccnc(Cl)n2)c1 | null | 68 | null |
803,022 | ord_dataset-ed846b4b229e4bb09ad9dba95ad7ebeb | null | 2008-01-01T00:01:00 | true | [CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]2[CH:14]=[C:13]([C:15]([OH:17])=O)[NH:12][C:9]2=[CH:10][N:11]=1.Cl.Cl.[CH:20]([N:23]1[CH2:28][CH2:27][CH:26]([NH2:29])[CH2:25][CH2:24]1)([CH3:22])[CH3:21].CN(C=O)C.CCN(C(C)C)C(C)C>>[CH:20]([N:23]1[CH2:28][CH2:27][CH:26]([NH:29][C:15]([C:13]2[NH:12][C:9]3=[CH:10][N:11]=[C:6]([O:5][CH2:4][CH2:3][O:2][CH3:1])[CH:7]=[C:8]3[CH:14]=2)=[O:17])[CH2:25][CH2:24]1)([CH3:22])[CH3:21] | CC(C)N1CCC(N)CC1 | COCCOc1cc2cc(C(=O)O)[nH]c2cn1 | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(C(C)C)C(C)C | CN(C)C=O | null | null | null | null | null | null | null | null | null | 25 | 4 | To a solution of 820 mg (3.47 mmol) of 5-(2-Methoxy-ethoxy)-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid and 745 mg (3.47 mmol) 1-isopropyl-piperidin-4-ylamine dihydrochloride in 30 mL absolute DMF 1.13 g (3.47 mmol) TOTU and 1.81 mL (10.41 mmol) DIPEA were added and the mixture was stirred for 4 h at room temperature. The solvent was removed in vacuo, the residue dissolved in CH2Cl2 and the CH2Cl2 phase washed with a saturated NaHCO3 solution. The organic phase was concentrated and the residue purified by chromatography over silica gel using CH2Cl2/MeOH/HOAc/H2O=90/10/1/1 as eluent. The fractions containing the product were combined and concentrated. The residue was dissolved in CH2Cl2 and the CH2Cl2 phase was washed with a saturated NaHCO3 solution. The phases were separated and the organic phase dried over Na2SO4. After filtration the solvent was removed in vacuo. Yield: 461 mg. | COCCOc1cc2cc(C(=O)NC3CCN(C(C)C)CC3)[nH]c2cn1 | null | null | null |
1,193,258 | ord_dataset-4e81c470cc3b429faf5e1caa50f70a98 | null | 2012-01-01T00:08:00 | true | [CH2:1]([O:3][C:4](=[O:42])[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([O:12][C:13]2[CH:18]=[CH:17][C:16](B3OC(C)(C)C(C)(C)O3)=[CH:15][C:14]=2[CH2:28][N:29]2[C@@H:33]([CH3:34])[C@@H:32]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[O:31][C:30]2=[O:41])[CH:7]=1)[CH3:2].Br[C:44]1[NH:45][CH:46]=[C:47]([CH3:49])[N:48]=1>>[CH2:1]([O:3][C:4](=[O:42])[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([O:12][C:13]2[CH:18]=[CH:17][C:16]([C:44]3[NH:45][CH:46]=[C:47]([CH3:49])[N:48]=3)=[CH:15][C:14]=2[CH2:28][N:29]2[C@@H:33]([CH3:34])[C@@H:32]([C:35]3[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=3)[O:31][C:30]2=[O:41])[CH:7]=1)[CH3:2] | Cc1c[nH]c(Br)n1 | CCOC(=O)Cc1cccc(Oc2ccc(B3OC(C)(C)C(C)(C)O3)cc2CN2C(=O)O[C@H](c3ccccc3)[C@@H]2C)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Prepared according to the procedure described in Example 19, Step 3, using the following starting materials: {3-[2-((4S,5R)-4-methyl-2-oxo-5-phenyl-oxazolidin-3-ylmethyl)-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenoxy]-phenyl}-acetic acid ethyl ester and 2-bromo-4-methyl-1H-imidazole. | CCOC(=O)Cc1cccc(Oc2ccc(-c3nc(C)c[nH]3)cc2CN2C(=O)O[C@H](c3ccccc3)[C@@H]2C)c1 | null | null | null |
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