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 ⌀ |
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140,560 | ord_dataset-a2a0fbbcd49a46ffaa432d7ceae8a506 | null | 1986-01-01T00:02:00 | true | [NH:1]1[CH:5]=[N:4][CH:3]=[N:2]1.Cl.[CH3:7][CH:8]1[CH2:12]OC(=O)[O:9]1>>[OH:9][CH:8]([CH3:12])[CH2:7][N:1]1[CH:5]=[N:4][CH:3]=[N:2]1 | c1nc[nH]n1 | CC1COC(=O)O1 | null | Cl | 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 | null | The starting material may be prepared as follows. A mixture of 1,2,4-triazole (5 g.) and 4-methyl-1,3-dioxolan-2-one was heated at 150° for 18 hours. Concentrated aqueous hydrochloric acid (8 ml.) was added dropwise to the ice-cooled mixture and the mixture was washed with chloroform. The aqueous phase was neutralised with aqueous potassium carbonate solution and extracted with chloroform, and the chloroform extract was dried and evaporated to dryness to give 1-(2-hydroxypropyl)-1,2,4-triazole (7.8 g.) which was characterised as the hydrogen oxalate, m.p. 110°-112° (after crystallisation from EtOH). | CC(O)Cn1cncn1 | null | null | null |
1,135,960 | ord_dataset-aaeaab5f3720492494c1cbbdd0ed2820 | null | 2012-01-01T00:02:00 | true | [CH3:1][O:2][CH2:3][CH2:4][NH:5][C:6]([N:8]1[CH2:13][CH:12]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=2)[CH2:11][CH:10]([C:24](O)=[O:25])[CH2:9]1)=[O:7].O[N:28]=[C:29]([NH2:33])[CH:30]([CH3:32])[CH3:31]>>[CH3:1][O:2][CH2:3][CH2:4][NH:5][C:6]([N:8]1[CH2:13][CH:12]([C:14]2[CH:15]=[CH:16][C:17]([C:20]([F:23])([F:21])[F:22])=[CH:18][CH:19]=2)[CH2:11][CH:10]([C:24]2[O:25][N:33]=[C:29]([CH:30]([CH3:32])[CH3:31])[N:28]=2)[CH2:9]1)=[O:7] | COCCNC(=O)N1CC(C(=O)O)CC(c2ccc(C(F)(F)F)cc2)C1 | CC(C)C(N)=NO | 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 | 100 mg (0.267 mmol) of the compound from Example 105A and 51 mg (0.497 mmol) of N′-hydroxy-2-methylpropanimidamide were reacted according to the General Method 2. Diastereomer separation of 83 mg of the cis/trans isomer mixture according to Method 14C gave 60.5 mg of the title compound and 6.7 mg of the trans isomer. | COCCNC(=O)N1CC(c2ccc(C(F)(F)F)cc2)CC(c2nc(C(C)C)no2)C1 | null | 51.4 | null |
1,660,647 | ord_dataset-42cd9bc5aae3485f9a58f1527bd3abf0 | null | 2015-01-01T00:11:00 | true | [C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:16][OH:17])[CH2:10][CH2:11][C:12]([O:14][CH3:15])=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:18]1([CH3:28])[CH:23]=[CH:22][C:21]([S:24](Cl)(=[O:26])=[O:25])=[CH:20][CH:19]=1.C(N(CC)CC)C>C(Cl)Cl>[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:16][O:17][S:24]([C:21]1[CH:22]=[CH:23][C:18]([CH3:28])=[CH:19][CH:20]=1)(=[O:26])=[O:25])[CH2:10][CH2:11][C:12]([O:14][CH3:15])=[O:13])=[O:7])([CH3:2])([CH3:4])[CH3:3] | COC(=O)CC[C@@H](CO)NC(=O)OC(C)(C)C | Cc1ccc(S(=O)(=O)Cl)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | CCN(CC)CC | null | null | null | null | null | null | null | null | null | 25 | 8 | Methyl (4S)-4-[(tert-butoxy)carbonylamino]-5-hydroxypentanoate (9.11 mmol, 2.25 g) was dissolved in 30 mL of methylene chloride. p-Toluenesulfonyl chloride (9.1 mmol, 1.7 g) and triethylamine (27.33 mmol, 3.8 mL) were added and the reaction was stirred at room temperature overnight. Solvent was removed in vacuo and crude was purified by column chromatography (SiO2, 4:1 n-hexanes/ethyl acetate to 7:3 n-hexanes/ethyl acetate) to yield the title compound (1.98 g, 54% yield). ES-MS: 402 (M+1). | COC(=O)CC[C@@H](COS(=O)(=O)c1ccc(C)cc1)NC(=O)OC(C)(C)C | null | 54.2 | null |
889,291 | ord_dataset-11068b1e475b4c5b82e56726ab0dddb7 | null | 2009-01-01T00:07:00 | true | [Br:1][C:2]1[C:3]([F:12])=[C:4]([F:11])[C:5](F)=[C:6]([CH:9]=1)[CH:7]=[O:8].C(N(CC)CC)C.[CH3:20][C@H:21]1[O:26][C@H:25]([CH3:27])[CH2:24][NH:23][CH2:22]1.Cl>C(#N)C>[Br:1][C:2]1[C:3]([F:12])=[C:4]([F:11])[C:5]([N:23]2[CH2:22][CH:21]([CH3:20])[O:26][CH:25]([CH3:27])[CH2:24]2)=[C:6]([CH:9]=1)[CH:7]=[O:8] | O=Cc1cc(Br)c(F)c(F)c1F | C[C@@H]1CNC[C@@H](C)O1 | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC#N | CCN(CC)CC | null | null | null | null | null | null | null | null | null | 25 | null | 5-Bromo-2,3,4-trifluoro-benzaldehyde (10 g, 41.8 mmol) was dissolved in dry acetonitrile (70 mL). Triethylamine (6.4 mL, 46.0 mmol) was added, followed by trans-2,6-dimethylmorpholine (BASF, 5.3 g, 46 mmol). The mixture was refluxed for 24 hours, then cooled to room temperature, and treated with 1N HCl (58 mL). The acetonitrile was removed by rotoevaporation and the resulting solids were filtered, washed with water then dissolved in THF (100 mL). The solution was dried over MgSO4 and concentrated to a yellow oil. Hexanes were added and the mixture was re-concentrated to give 12.66 g of a yellow powder. 1H NMR (400 MHz, CHLOROFORM-d) d ppm 1.26 (d, J=6.4 Hz, 6H), 2.92 (m, 2H), 3.28 (d, J=11.7 Hz, 2H), 4.15 (m, 2H), 7.78 (dd, J=7.2, 2.3 Hz, 2H), 10.32 (s, 4H). | CC1CN(c2c(C=O)cc(Br)c(F)c2F)CC(C)O1 | null | 90.6 | null |
1,471,894 | ord_dataset-fd1fa959d6264608b0b7fcda16741bfd | null | 2014-01-01T00:08:00 | true | CS(O[CH:6]1[CH2:11][CH2:10][CH2:9][N:8]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[O:19][CH:20]=[CH:21][N:22]=3)=[CH:14][CH:13]=2)[CH2:7]1)(=O)=O.[NH2:23][C@@H:24]1[CH2:29][CH2:28][CH2:27][CH2:26][C@H:25]1[NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34]>C(#N)C>[O:19]1[CH:20]=[CH:21][N:22]=[C:18]1[C:15]1[CH:16]=[CH:17][C:12]([N:8]2[CH2:9][CH2:10][CH2:11][CH:6]([NH:23][C@@H:24]3[CH2:29][CH2:28][CH2:27][CH2:26][C@H:25]3[NH:30][C:31](=[O:37])[O:32][C:33]([CH3:35])([CH3:34])[CH3:36])[CH2:7]2)=[CH:13][CH:14]=1 | CS(=O)(=O)OC1CCCN(c2ccc(-c3ncco3)cc2)C1 | CC(C)(C)OC(=O)N[C@@H]1CCCC[C@H]1N | 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 | 120 | 0.5 | To a solution of 1-(4-(oxazol-2-yl)phenyl)piperidin-3-yl methane sulfonate (110 mg, 0.341 mmol) in acetonitrile (4 mL) was added tert-butyl (1R,2R)-2-aminocyclohexylcarbamate (110 mg, 0.512 mmol). The reaction was stirred in a microwave at 120° C. for 30 min. After this time, LC/MS showed two pairs of products formed. The reaction mixture was concentrated. The residue was diluted with EtOAc and washed with water. The remaining EtOAc organic layer was concentrated. The resulting residue was purified using silica gel chromatography (ISCO system) eluting with a gradient of 50-100% EtOAc/Hex. Under these conditions, the two diastereomers separated and the desired diastereomer tert-butyl (1R,2R)-2-((1-(4-(oxazol-2-yl)phenyl)pyrrolidin-2-yl)methylamino)cyclohexylcarbamate (156 mg total) as a white foam. | CC(C)(C)OC(=O)N[C@@H]1CCCC[C@H]1NC1CCCN(c2ccc(-c3ncco3)cc2)C1 | null | null | null |
713,931 | ord_dataset-c8a367b56b4f406b878f51867b157d19 | null | 2006-01-01T00:06:00 | true | C[O:2][C:3]1[C:4]([CH3:36])=[C:5]([C:27]([O:34]C)=[C:28]([O:32][CH3:33])[C:29]=1[O:30][CH3:31])[CH2:6][C:7]1[CH:8]=[CH:9][C:10]([O:21][CH2:22][C:23]([O:25][CH3:26])=[O:24])=[C:11]([CH:20]=1)[C:12]([N:14]1[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1)=[O:13].O=[N+]([O-])[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[Ce+4].[NH4+].[NH4+]>C(#N)C.O>[CH3:31][O:30][C:29]1[C:3](=[O:2])[C:4]([CH3:36])=[C:5]([CH2:6][C:7]2[CH:8]=[CH:9][C:10]([O:21][CH2:22][C:23]([O:25][CH3:26])=[O:24])=[C:11]([CH:20]=2)[C:12]([N:14]2[CH2:15][CH2:16][O:17][CH2:18][CH2:19]2)=[O:13])[C:27](=[O:34])[C:28]=1[O:32][CH3:33] | COC(=O)COc1ccc(Cc2c(C)c(OC)c(OC)c(OC)c2OC)cc1C(=O)N1CCOCC1 | null | null | O=[N+]([O-])[O-] | [Ce+4] | [NH4+] | 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-[5-(3,4,5,6-Tetramethoxy-2-methylbenzyl)-2-(methoxycarbonylmethyloxy)benzoyl]morpholine (0.240 g, 0.478 mmol) was dissolved in a mixed solution of acetonitrile (12 ml) and water (4 ml) and after adding thereto CAN (0.655 g, 1.20 mmol) at room temperature, the solution was stirred at room temperature for 1 hour. The reaction solution was diluted with water and then extracted with ether. The extract was washed with water and then dried, and the solvent was removed by distillation. The obtained residue was purified by preparative thin-layer chromatography (hexand:ethyl acetate=1:3) to obtain the titled compound (0.180 g, 0.381 mmol, 80%). | COC(=O)COc1ccc(CC2=C(C)C(=O)C(OC)=C(OC)C2=O)cc1C(=O)N1CCOCC1 | null | 79.7 | null |
69,124 | ord_dataset-cb0fdfa937234c78b020ec878a93b94c | null | 1980-01-01T00:08:00 | true | C([NH:8][CH:9]([CH:11]1[O:16][C:15]2[CH:17]=[CH:18][CH:19]=[CH:20][C:14]=2[O:13][CH2:12]1)[CH3:10])C1C=CC=CC=1>CO.Cl.[Pd]>[O:16]1[C:15]2[CH:17]=[CH:18][CH:19]=[CH:20][C:14]=2[O:13][CH2:12][CH:11]1[CH:9]([NH2:8])[CH3:10] | CC(NCc1ccccc1)C1COc2ccccc2O1 | 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 | null | In 50 ml of methanol was dissolved 7 g of pure N-benzyl-1-(1,4-benzodioxan-2-yl)ethylamine (i1 '). After adding one drop of ethanolic hydrochloric acid and 0.5 g of 10% palladium charcoal to the solution, and catalytic reduction was performed at normal pressure until the absorption of hydrogen gas stopped. Then, palladium charcoal was filtered away, the filtrate was acidified with the addition of ethanolic hydrochloric acid, and the solvent was distilled off. Then, 20 ml of isopropanol was added to the residue and the product formed was recovered by filtration to provide 4.4 g (75.7%) of 1-(1,4-benzodioxan-2-yl)ethylamine (i1 ') hydrochloride having a melting point of 234°-235° C. The product was then converted into a base by a conventional manner and distilled under reduced pressure to provide 2.9 g (62.3%) of 1-(1,4-benzodioxan-2-yl)ethylamine (i1 ') having a boiling point of 88°-90° C./0.1 mmHg. | CC(N)C1COc2ccccc2O1 | null | 94.5 | null |
1,220,022 | ord_dataset-dc3bb1b1ac4e4229a3fc28fb559a9777 | null | 2012-01-01T00:10:00 | true | [F:1][C:2]1[CH:38]=[CH:37][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]4[CH:29]=[CH:28][N:27]=[C:26]5[NH:30][N:31]=[CH:32][C:25]=45)=[CH:19][CH:18]=3)=[O:15])=[CH:9][C:8]=2[C:33]([F:36])([F:35])[F:34])=[CH:4][CH:3]=1.CC[C:41]([C:43](Cl)=[O:44])=[O:42]>ClCCl.C1COCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([N:13]3[C:41](=[O:42])[C:43](=[O:44])[N:16]([C:17]4[CH:18]=[CH:19][C:20]([O:23][C:24]5[CH:29]=[CH:28][N:27]=[C:26]6[NH:30][N:31]=[CH:32][C:25]=56)=[CH:21][CH:22]=4)[C:14]3=[O:15])=[CH:9][C:8]=2[C:33]([F:35])([F:36])[F:34])=[CH:37][CH:38]=1 | CCC(=O)C(=O)Cl | O=C(Nc1ccc(Oc2ccnc3[nH]ncc23)cc1)Nc1ccc(Oc2ccc(F)cc2)c(C(F)(F)F)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | C1CCOC1 | null | null | null | null | null | null | null | null | null | 70 | 3 | 1-[4-(4-Fluorophenoxy)-3-trifluoromethyl-phenyl]-3-[4-(1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl]urea (50 mg, 0.15 mmol) was dissolved in dichloromethane (5 mL) and THF (3 mL), and ethyloxalyl chloride (70 μL) was added thereto. The resulting mixture was stirred at 70° C. for 3 hours. The reaction solution was concentrated and then purified by reverse-phase HPLC (ODS column, 0.05% TFA-containing water/acetonitrile system, 5% to 95% linear gradient) to give the target compound (9 mg, 20%). | O=C1C(=O)N(c2ccc(Oc3ccc(F)cc3)c(C(F)(F)F)c2)C(=O)N1c1ccc(Oc2ccnc3[nH]ncc23)cc1 | null | 20 | null |
233,427 | ord_dataset-ed79ebfb2fff4cdbbc3a609c8edeac11 | null | 1991-01-01T00:08:00 | true | [Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][CH:3]=1.Cl.[H][H]>>[CH:10]1[C:11]2[C:6](=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH:7]=[CH:8][CH:9]=1.[ClH:1] | Clc1cccc2ccccc12 | [H][H] | null | Cl | 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 | High conversions of 1-chloro- or 1-bromonaphthalene coupled with a long catalyst life can be achieved by the zeolites used according to the invention. The conversion of 1-chloronaphthalene over an amorphous aluminosilicate, in spite of an HCl atmosphere, dropped from 51 to 41% in the course of 4 hours (temperature 400° C., LHSV 0.2 h-1, N. N. Vorozhtsov, Jr. and A. M. Beskin, J. Gen. Chem. USSR, 24, 667/672 (1954) English edition). In contrast, an HEU-1 zeolite converted 56% of 1-chloro-naphthalene after 1 hour and 41% after 7 hours in a hydrogen atmosphere at the same temperature but 2.5 times the LHSV. The selectivity for the isomerization of 1-chloronaphthalene over HEU-1 is very high and is more than 98% at reaction temperatures of between 300° and 400° C. Naphthalene above all is formed as a by-product by elimination of HCl. Less than 0.05% of dichloronaphthalenes is formed. In the reaction of 1-bromonaphthalene, however, transbromination to naphthalene and dibromonaphthalenes occurs. The selectivity for 2-bromo-naphthalene is nevertheless very high, at 95% at 350° C. and 50% conversion. | c1ccc2ccccc2c1 | null | null | null |
1,315,632 | ord_dataset-2d6edb8ffd434003bb508360153bd9bb | null | 2013-01-01T00:07:00 | true | [CH:1]([NH2:4])([CH3:3])[CH3:2].[I-].[Na+].CS(O[CH2:12][C:13]1[CH:14]=[C:15]([NH:23][C:24]([N:26]2[C:34]3[C:29](=[CH:30][C:31]([O:35][C:36]4[C:37]5[CH2:45][CH2:44][N:43](C(OC(C)(C)C)=O)[CH2:42][C:38]=5[N:39]=[CH:40][N:41]=4)=[CH:32][CH:33]=3)[CH:28]=[CH:27]2)=[O:25])[CH:16]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:18]=1)(=O)=O>C(Cl)Cl>[CH:1]([NH:4][CH2:12][C:13]1[CH:14]=[C:15]([NH:23][C:24]([N:26]2[C:34]3[C:29](=[CH:30][C:31]([O:35][C:36]4[C:37]5[CH2:45][CH2:44][NH:43][CH2:42][C:38]=5[N:39]=[CH:40][N:41]=4)=[CH:32][CH:33]=3)[CH:28]=[CH:27]2)=[O:25])[CH:16]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:18]=1)([CH3:3])[CH3:2] | CC(C)(C)OC(=O)N1CCc2c(ncnc2Oc2ccc3c(ccn3C(=O)Nc3cc(COS(C)(=O)=O)cc(C(F)(F)F)c3)c2)C1 | CC(C)N | null | [I-] | [Na+] | 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 | 0.75 | To a solution of the above mixture (0.15 g, 0.227 mmol) in 3 mL of DCM, isopropyl amine (0.06 mL, 0.680 mmol) is added followed by sodium iodide (0.1 g, 0.68 mmol). After 45 min, LC-MS shows that tert-butyl 4-(1-(3-((methylsulfonyloxy)methyl)-5-(trifluoromethyl)phenylcarbamoyl)-1H-indol-5-yloxy)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate is converted to desired product and the tert-butyl 4-(1-(3-(chloromethyl)-5-(trifluoromethyl)phenylcarbamoyl)-1H-indol-5-yloxy)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate left over. To the reaction 3 mL (0.227 mmol) of isopropyl amine is added followed by NaI (0.1 g, 0.68 mmol) and the mixture is heated to 45° C. for 2 h. The solvent is then removed and the residue diluted with EtOAc, washed with H2O, brine and the organic layer dried over Na2SO4. Following concentration the residue is separated by FCC (25-100% EtOAc/heptane). This product is then treated with 60 mL of 50% TFA/DCM at rt for 1.5 h. After concentration the residue is separated by semi-prep HPLC (C-18; 10-100% I/H2O with 0.1% NH4OH) to provide the title compound. MS (ESI) m/z 525.2 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 10.33 (s, 1H), 8.40 (s, 1H), 8.27 (d, J=8.8 Hz, 1H), 8.13 (d, J=3.8 Hz, 1H), 7.95 (d, J=15.2 Hz, 2H), 7.38-7.52 (m, 2H), 7.11 (dd, J=9.0, 2.4 Hz, 1H), 6.78 (d, J=3.8 Hz, 1H), 3.81 (d, J=7.6 Hz, 4H), 3.03 (t, J=5.8 Hz, 2H), 2.68-2.79 (m, 3H), 1.03 (d, J=6.1 Hz, 6H). | CC(C)NCc1cc(NC(=O)n2ccc3cc(Oc4ncnc5c4CCNC5)ccc32)cc(C(F)(F)F)c1 | null | null | null |
13,754 | ord_dataset-7f88a5da29d74264aae5239be74b3981 | null | 1976-01-01T00:10:00 | true | CC(O[CH2:5][C:6]1[CH2:15][S:14][C@@H:9]2[C@H:10]([NH2:13])[C:11](=[O:12])[N:8]2[C:7]=1[C:16]([OH:18])=[O:17])=O.[SH:19][C:20]1[N:24]([CH3:25])[CH:23]=[N:22][N:21]=1>>[NH2:13][CH:10]1[C:11](=[O:12])[N:8]2[C:7]([C:16]([OH:18])=[O:17])=[C:6]([CH2:5][S:19][C:20]3[N:24]([CH3:25])[CH:23]=[N:22][N:21]=3)[CH2:15][S:14][C@H:9]12 | Cn1cnnc1S | CC(=O)OCC1=C(C(=O)O)N2C(=O)[C@@H](N)[C@H]2SC1 | 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 | 7-Amino-3-(4-methyl-1,2,4-triazol-3-ylthiomethyl)-3-cephem-4-carboxylic acid was prepared from 7-ACA and 3-mercapto-4-methyl-1,2,4-triazole according to the first paragraph of Example 1. | Cn1cnnc1SCC1=C(C(=O)O)N2C(=O)C(N)[C@H]2SC1 | null | null | null |
1,542,029 | ord_dataset-cac8df8aff894288876df4e093c9877f | null | 2015-01-01T00:02:00 | true | [F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH:5]=O.C(O)(=O)[CH2:11][C:12]([OH:14])=[O:13].N1CCCCC1>N1C=CC=CC=1>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:11][C:12]([OH:14])=[O:13])[CH:7]=[CH:8][CH:9]=1 | O=Cc1cccc(F)c1 | O=C(O)CC(=O)O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCNCC1 | c1ccncc1 | null | null | null | null | null | null | null | null | null | null | null | 3-Fluorobenzaldehyde (5 g, 40.28 mmol) in pyridine (50 mL) was reacted with malonic acid (5.4 g, 52.3 mmol) and piperidine (343 mg, 4.0 mmol) at 75° C. for 12 hours to afford 6.6 g (96.9%) of the crude product which was used in the next step without further purification. | O=C(O)C=Cc1cccc(F)c1 | null | 98.6 | null |
1,524,951 | ord_dataset-8c74302143c04eb9983e4b3a7ead2d72 | null | 2014-01-01T00:12:00 | true | Cl[CH2:2][C:3]#[N:4].BrCC1CCCCO1.[NH:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15]2([C:25]3=[CH:26][C:27]4[O:31][CH2:30][O:29][C:28]=4[CH:32]=[C:24]3[O:23][CH2:22]2)[C:14]1=[O:33]>>[O:33]=[C:14]1[C:15]2([C:25]3=[CH:26][C:27]4[O:31][CH2:30][O:29][C:28]=4[CH:32]=[C:24]3[O:23][CH2:22]2)[C:16]2[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=2)[N:13]1[CH2:2][C:3]#[N:4] | N#CCCl | O=C1Nc2ccccc2C12COc1cc3c(cc12)OCO3 | null | BrCC1CCCCO1 | 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 | Following the procedure as described in EXAMPLE 4 and making non-critical variations using chloroacetonitrile to replace 2-(bromomethyl)tetrahydro-2H-pyran, and spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one to replace 5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-2″(1′H)-one, (2′-oxospiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-1′(2′H)-yl)acetonitrile was obtained (61%) as a colorless solid: mp 170-172° C.; 1H NMR (300 MHz, DMSO-d6) δ7.38 (dt, J=7.7, 1.2 Hz, 1H), 7.26 (d, J=7.7 Hz, 1H), 7.20 (d, J=7.3 Hz, 1H), 7.11 (dt, J=7.7, 1.1 Hz, 1H), 6.66 (s, 1H), 6.21 (s, 1H), 5.89 (d, J=1.5 Hz, 2H), 4.94 (ABq, J=17.9 Hz, 2H), 4.73 (ABq, J=9.5 Hz, 2H); 13C NMR (75 MHz, DMSO-d6) δ176.8, 155.8, 148.9, 142.232, 141.0, 131.9, 129.4, 124.3, 124.3, 119.8, 116.0, 109.7, 103.5, 101.9, 93.8, 80.1, 57.8, 28.8; MS (ES+) m/z 321.3 (M+1). | N#CCN1C(=O)C2(COc3cc4c(cc32)OCO4)c2ccccc21 | null | null | null |
1,384,166 | ord_dataset-31641fb65b34430fa7435229b949b604 | null | 2014-01-01T00:01:00 | true | [CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([NH2:15])=[CH:11][CH:10]=2)[CH2:4][CH2:3]1.Cl[C:17]1([C:29]2[C:30]([O:35][CH2:36][CH3:37])=[N:31][CH:32]=[CH:33][CH:34]=2)[C:25]2[C:20](=[CH:21][CH:22]=[C:23]([C:26]#[N:27])[CH:24]=2)[NH:19][C:18]1=[O:28].CCN(C(C)C)C(C)C.C([O-])(O)=O.[Na+]>ClCCl>[CH2:36]([O:35][C:30]1[C:29]([C:17]2([NH:15][C:12]3[CH:13]=[CH:14][C:9]([CH2:8][N:5]4[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]4)=[CH:10][CH:11]=3)[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:26]#[N:27])[CH:24]=3)[NH:19][C:18]2=[O:28])=[CH:34][CH:33]=[CH:32][N:31]=1)[CH3:37] | CN1CCN(Cc2ccc(N)cc2)CC1 | CCOc1ncccc1C1(Cl)C(=O)Nc2ccc(C#N)cc21 | null | O=C([O-])O | [Na+] | null | 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 | 2 | 4-(4-Methyl-piperazin-1-ylmethyl)phenylamine (425 mg, 2.07 mmol) was added to a solution of 3-chloro-3-(2-ethoxypyridin-3-yl)-2-oxo-2,3-dihydro-1H-indole-5-carbonitrile (500 mg, 1.59 mmol) in dichloromethane (50 ml) and DIPEA (0.27 ml, 159 mmol) at 0° C. The reaction mixture was stirred at room temperature for 2 h and then an aqueous NaHCO3 solution was added. The aqueous reaction mixture was extracted with dichloromethane. The combined organic phase was dried over magnesium sulfate, filtered and concentrated at reduced pressure. Purification by chromatography (silica gel, 0-20% methanol in dichloromethane) afforded 791 mg of the title compound (99% yield). | CCOc1ncccc1C1(Nc2ccc(CN3CCN(C)CC3)cc2)C(=O)Nc2ccc(C#N)cc21 | null | 103.1 | null |
558,369 | ord_dataset-f483e698250b4da0a84f425c7bfa965a | null | 2002-01-01T00:08:00 | true | [CH3:1][C:2]1([CH3:16])[C:7]2[CH:8]=[C:9](B(O)O)[CH:10]=[CH:11][C:6]=2[NH:5][C:4](=[O:15])[O:3]1.Br[C:18]1[N:23]=[C:22]([CH2:24][C:25]#[N:26])[CH:21]=[CH:20][CH:19]=1>>[CH3:1][C:2]1([CH3:16])[C:7]2[CH:8]=[C:9]([C:18]3[N:23]=[C:22]([CH2:24][C:25]#[N:26])[CH:21]=[CH:20][CH:19]=3)[CH:10]=[CH:11][C:6]=2[NH:5][C:4](=[O:15])[O:3]1 | CC1(C)OC(=O)Nc2ccc(B(O)O)cc21 | N#CCc1cccc(Br)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 | [6-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)pyridin-2-yl]acetonitrile was prepared, according to the procedure of Example 5 using (1,4-dihydro-4,4-dimethyl-2-oxo-2H-3,1-benzoxazin-6-yl)boronic acid and (6-bromo-2-pyridyl)acetonitrile (J. Org. Chem. 1988, 53, 786-790), as an off-white solid: mp 210-212.5° C.; 1H NMR (DMSO-d6) δ1.68 (s, 6H), 4.27 (s, 2H), 7.00 (d, 1H, J=8.3 Hz), 7.34 (d, 1H, J=7.1 Hz), 7.89-7.96 (m, 2H), 8.00-8.05 (m, 2H), 10.42 (s, 1H); MS (ESI) [M−H]−=292; Anal. Calcd. For C17H15N3O2: C, 69.61; H, 5.15; N, 14.33. Found: C, 68.49; H, 5.19; N, 13.74. | CC1(C)OC(=O)Nc2ccc(-c3cccc(CC#N)n3)cc21 | null | null | null |
662,884 | ord_dataset-5a3d853c53674888a5691dce2e398792 | null | 2005-01-01T00:03:00 | true | CC1(C)C(C)(C)OB([C:9]2[CH:17]=[CH:16][CH:15]=[C:14]3[C:10]=2[CH:11]=[CH:12][NH:13]3)O1.Br[C:20]1[CH:21]=[C:22]([CH2:26][C:27]([OH:29])=[O:28])[CH:23]=[CH:24][CH:25]=1.[OH-].[Na+]>C1COCC1.[Pd].C(OCC)(=O)C>[NH:13]1[C:14]2[C:10](=[C:9]([C:20]3[CH:21]=[C:22]([CH2:26][C:27]([OH:29])=[O:28])[CH:23]=[CH:24][CH:25]=3)[CH:17]=[CH:16][CH:15]=2)[CH:11]=[CH:12]1 | O=C(O)Cc1cccc(Br)c1 | CC1(C)OB(c2cccc3[nH]ccc23)OC1(C)C | null | [Pd] | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | CCOC(C)=O | null | null | null | null | null | null | null | null | null | 70 | null | To a mixture of 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-indole (15.52 g, 63.72 mmol), and 3-bromo-phenylacetic acid (13.78 g, 63.72 mmol) in THF (192 mL) were added Palladium catalyst Pd(PPh3)4 (2.21 g, 1.9 mmol) and the freshly prepared sodium hydroxide solution (7.65 g in 90 mL of water). The system was degassed and then charged with nitrogen. The degas procedure was repeated for three times. The mixture was stirred under nitrogen in a 70° C. oil bath for over the weekend. TLC showed the completion of the coupling reaction. The mixture was cooled to room temperature, diluted with ethyl acetate, and separated from water layer. The water layer was acidified with dil. HCl solution to pH 4-5 and extracted with ethyl acetate. The ethyl acetate solution was washed with water, brine, and dried over Na2SO4. After filtration, the solvents were evaporated, and the crude product was purified on a silica gel column to give 13.5 g (84%) of [3-(1H-indol-4-yl)-phenyl]-acetic acid. | O=C(O)Cc1cccc(-c2cccc3[nH]ccc23)c1 | null | 84.3 | null |
1,705,056 | ord_dataset-54347fcace774f89850681d6dec8009f | null | 2016-01-01T00:03:00 | true | [Br:1][C:2]1[C:10]2[O:9][CH:8]=[C:7]([CH3:11])[C:6]=2[C:5]([F:12])=[C:4]([F:13])[CH:3]=1.C1C(=O)[N:18](Br)[C:16](=O)C1.[C-]#N.[Na+].[OH-].[Na+]>O.C(Cl)(Cl)(Cl)Cl>[Br:1][C:2]1[C:10]2[O:9][CH:8]=[C:7]([CH2:11][C:16]#[N:18])[C:6]=2[C:5]([F:12])=[C:4]([F:13])[CH:3]=1 | Cc1coc2c(Br)cc(F)c(F)c12 | O=C1CCC(=O)N1Br | null | [C-]#N | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | ClC(Cl)(Cl)Cl | null | null | null | null | null | null | null | null | null | 50 | 0.5 | To the compound (98.8 mg, 0.400 mmol) of Step 1 of Example 21, NBS (78.3 mg, 0.440 mmol), and a catalytic amount of BPO, carbon tetrachloride (4 mL) was added, and heated under reflux overnight. The resultant was returned to room temperature, and the solvent was distilled away under reduced pressure. The resulting residue was diluted with dichloromethane, washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled away under reduced pressure. The resulting residue was dissolved in acetonitrile (2 mL), and sodium cyanide (39.2 mg, 0.800 mmol) and water (0.2 mL) were added thereto, and stirred at 50° C. for 30 minutes. To the reaction solution, a 1 N sodium hydroxide aqueous solution was added. After concentrated under reduced pressure, the resultant was diluted with ethyl acetate, washed with water and saturated brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled away under reduced pressure. The resulting residue was purified by silica gel chromatography to thus obtain the title compound. | N#CCc1coc2c(Br)cc(F)c(F)c12 | null | 36 | null |
332,277 | ord_dataset-1558660634294cc8ad7e01746e9083fd | null | 1996-01-01T00:06:00 | true | C([Li])CCC.[C:6]1([O:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.CN(C)[CH:21]=[O:22].OS(O)(=O)=O>CCOCC>[O:12]([C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][C:11]=1[CH:21]=[O:22])[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1 | c1ccc(Oc2ccccc2)cc1 | CN(C)C=O | null | O=S(=O)(O)O | [Li]CCCC | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOCC | null | null | null | null | null | null | null | null | null | null | 0 | 1.5 | At room temperature, under an argon atmosphere, n-butyllithium (15.45 mL of a 2.5M solution in hexanes, 38.61 mmol) was added to a solution of diphenyl ether (5.0 g; 29.38 mmol) in 100 mL of ether, and the reaction mixture was gently refluxed for 4 hrs. After cooling to 0° C., N,N-dimethylformamide (22.73 mL; 0.293 mol) was added dropwise and the reaction was stirred for 15 min at 0° C. and 1.5 hr at room temperature. After adding 10% H2SO4 to pH 1, it was stirred for 15 min and extracted into ethyl acetate. Chromatography of the crude product (10% ethyl acetate/hexane) provided 4.0 g (69%) of the aldehyde, 1H NMR (CDCl3): δ 6.97 (d, 1H); 7.02-7.11 (m, 2H); 7.18-7.22 (m, 2H); 7.29 (t, 1H); 7.39 (t, 1H); 7.43 (t, 1H); 7.95 (t, 1H). | O=Cc1ccccc1Oc1ccccc1 | null | 68.7 | null |
364,332 | ord_dataset-c2ad1656a3ca4d08888ffb6e3f3a2742 | null | 1997-01-01T00:05:00 | true | [N:1]([CH2:4][CH2:5][CH2:6][CH2:7][C@H:8]1[C:13]([O:14][CH3:15])=N[C@H](C(C)C)C(OC)=[N:9]1)=[N+:2]=[N-:3].Cl.[OH2:22].N>O1CCOCC1>[NH2:9][C@@H:8]([CH2:7][CH2:6][CH2:5][CH2:4][N:1]=[N+:2]=[N-:3])[C:13]([O:14][CH3:15])=[O:22] | O | COC1=N[C@H](C(C)C)C(OC)=N[C@H]1CCCCN=[N+]=[N-] | null | Cl | N | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1COCCO1 | null | null | null | null | null | null | null | null | null | null | 25 | 8 | 1-Azido-4-[(2R,5S)-3,6-dimethoxy-2-isopropyl-2,5-dihydro-5-pyrazinyl]butane (2.17 g, 7.72 mmol) was dissolved in 30 ml dioxane and a solution of 1.28 ml conc. HCl in 30 ml water (15.45 mmol) was added dropwise, the mixture stirred under argon at ambient temperature overnight. Ammonia solution was added until pH 9 was reached, the solution extracted with chloroform, dried (MgSO4), and the valine methyl ester was removed by bulb-to-bulb distillation (0.05 torr, 25° C.). | COC(=O)[C@@H](N)CCCCN=[N+]=[N-] | null | null | null |
617,606 | ord_dataset-2952e63264f5422a84e12cca1e0541ee | null | 2003-01-01T00:12:00 | true | [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH2:9])=[CH:5][C:4]=1[O:10][CH2:11][CH2:12][C:13]1[CH:22]=[CH:21][C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)C=1.[C:23]1([CH:29]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:30](Cl)=[O:31])[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(N(CC)CC)C>CC(N(C)C)=O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:30](=[O:31])[CH:29]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[CH:5][C:4]=1[O:10][CH2:11][C:12]1[C:19]2[C:20](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH:21]=[CH:22][CH:13]=1 | COc1ccc(N)cc1OCCc1ccc2ccccc2c1 | O=C(Cl)C(c1ccccc1)c1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(=O)N(C)C | CCN(CC)CC | null | null | null | null | null | null | null | null | null | 25 | 16 | N-[4-methoxy-3-(naphthylmethoxy)phenyl]-2,2-diphenylethanamide (Exemplary Compound 49) was prepared using the same experimental conditions used to prepare Example 52 (Scheme X). From 4-methoxy-3-(2-naphthylethoxy)phenylamine (350 mg, 1.25 mmol) and diphenylacetyl chloride (290 mg, 1.25 mmol) in 10 mL of dimethyl acetamide containing triethylamine (1 mL, 7.17 mmol) stirred at room temperature for 16 h., was obtained 375 mg of product in (64%) yield as a white solid after recrystallization from ethyl acetate/hexane: mp 170-172° C. 1H NMR (400 MHz, Me2SO-d6) δ3.69 (s, 3H); 5.13 (s, 1H); 5.46 (s, 2H); 6.93 (d, 1H, J=8.7); 7.20-7.37 (m, 10H); 7.50-7.65 (m, 5H); 7.94-8.09 (m, 3H); 10.28 (s, 1H). Anal. Calcd for C32H27NO3: C, 81.16; H, 5.75; N, 2.96. Found: C, 80.95; H, 5.76; N, 3.03. | COc1ccc(NC(=O)C(c2ccccc2)c2ccccc2)cc1OCc1cccc2ccccc12 | null | null | null |
815,359 | ord_dataset-50f99930fc41474db226bc80774b38df | null | 2008-01-01T00:04:00 | true | [CH2:1]([N:8]1[CH2:13][CH2:12][O:11][CH:10]([C:14]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)([OH:24])CC2C(F)=CC=CC=2Cl)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:31][O:32][C:33]1[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][C:34]=1[CH2:35][Mg]Cl>>[CH2:1]([N:8]1[CH2:13][CH2:12][O:11][CH:10]([C:14]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)([OH:24])[CH2:35][C:34]2[CH:38]=[C:39]([O:42][CH3:43])[CH:40]=[CH:41][C:33]=2[O:32][CH3:31])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1 | OC(Cc1c(F)cccc1Cl)(c1ccccc1)C1CN(Cc2ccccc2)CCO1 | COc1ccc(OC)c(C[Mg]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 | The procedure for the synthesis of example 18a, 1-(4-Benzyl-morpholin-2-yl)-2-(2-chloro-6-fluoro-phenyl)-1-phenyl-ethanol, using 2,5-dimethoxybenzyl magnesium chloride as starting material (available from Rieke Metals) was followed making non-critical variations, to yield the title compound. This material was used in step b) without further purification. LCMS (6 minutes method) [M+H]+=434 @ Rt 3.10 min. major peak. | COc1ccc(OC)c(CC(O)(c2ccccc2)C2CN(Cc3ccccc3)CCO2)c1 | null | null | null |
1,389,509 | ord_dataset-31641fb65b34430fa7435229b949b604 | null | 2014-01-01T00:01:00 | true | [N:1]1[CH:6]=[C:5](/[CH:7]=[CH:8]/[C:9]([O:11][CH3:12])=[O:10])[CH:4]=[N:3][CH:2]=1>CO.[Pd]>[N:1]1[CH:6]=[C:5]([CH2:7][CH2:8][C:9]([O:11][CH3:12])=[O:10])[CH:4]=[N:3][CH:2]=1 | COC(=O)/C=C/c1cncnc1 | 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 | null | null | A solution of methyl (2E)-3-(5-pyrimidinyl)-2-propenoate (19.2 g, 117 mmol) and Pd/C (2 g, 1.879 mmol) in methanol (100 mL) was stirred under H2 at 50° C. overnight. The mixture was filtered through a pad of celite and concentrated to give the crude title compound as yellow oil (18 g, 55.6% yield). LCMS: rt=1.11 min, [M+H+]=167 | COC(=O)CCc1cncnc1 | null | 92.6 | null |
1,634,087 | ord_dataset-f0794d5ded7a4d3fab45cc3d7a89ee3d | null | 2015-01-01T00:09:00 | true | [CH2:1]([N:8]1[C:13]([CH3:15])([CH3:14])[CH2:12][N:11]([C:16]([C:18]2[CH:23]=[C:22]([C:24]3[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][C:25]=3OC)[N:21]=[C:20]3[N:34]([CH:38]4[CH2:43][CH2:42][CH2:41][CH2:40][O:39]4)[N:35]=[C:36]([CH3:37])[C:19]=23)=O)[C:10]([CH3:45])([CH3:44])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.B.CSC.C1C[O:53][CH2:52]C1>>[CH2:1]([N:8]1[C:13]([CH3:15])([CH3:14])[CH2:12][N:11]([CH2:16][C:18]2[CH:23]=[C:22]([C:24]3[CH:29]=[CH:28][C:27]([O:30][CH2:31][O:53][CH3:52])=[CH:26][CH:25]=3)[N:21]=[C:20]3[N:34]([CH:38]4[CH2:43][CH2:42][CH2:41][CH2:40][O:39]4)[N:35]=[C:36]([CH3:37])[C:19]=23)[C:10]([CH3:45])([CH3:44])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1 | COc1ccc(-c2cc(C(=O)N3CC(C)(C)N(Cc4ccccc4)CC3(C)C)c3c(C)nn(C4CCCCO4)c3n2)c(OC)c1 | C1CCOC1 | null | B | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CSC | null | null | null | null | null | null | null | null | null | null | null | null | To a solution of 1.54 g of (4-benzyl-2,2,5,5-tetramethyl-piperazin-1-yl)-[6-(4-methoxy-methoxy-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl]-methanone in 9 ml of dry THF 20 ml of borane-dimethylsulfide complex (1 M in DCM) was added slowly at r.t., and the reaction was heated to reflux for 12 h. The reaction was quenched by the addition of 13 ml of methanol, and the solvents were evaporated. The residue was purified by flash chromatography (silica, heptanes/ethyl acetate) yielding 1.44 g (96%) of the title compound. | COCOc1ccc(-c2cc(CN3CC(C)(C)N(Cc4ccccc4)CC3(C)C)c3c(C)nn(C4CCCCO4)c3n2)cc1 | null | 96 | null |
444,322 | ord_dataset-ba7561dae3884c07a8beddd0b9f1222e | null | 1999-01-01T00:10:00 | true | [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[OH:14])=[CH:4][CH:3]=1.[H-].[Na+].F[C:18]1[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][CH:19]=1.O>CN(C)C=O>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[O:14][C:18]2[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][CH:19]=2)=[CH:6][CH:7]=1 | O=[N+]([O-])c1ccc(F)cc1 | Cc1ccc(-c2ccccc2O)cc1 | null | [H-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | O | null | null | null | null | null | null | null | null | null | 25 | 0.5 | A solution of 184 mg (1.0 mmol) of 4-methyl-2'-hydroxy-1,1'-biphenyl (Example 12, Step C) in 3 mL of dimethylformamide was treated with 55 mg of 60% sodium hydride (33 mg NaH, 1.4 mmol). The reaction mixture was stirred at room temperature for 30 minutes then treated with 169 mg (1.19 mmol) of 1-fluoro-4-nitrobenzene. The reaction mixture was heated at 100° C. for 2 hours. The reaction mixture was cooled, poured into 50 mL of water and the resultant mixture was extracted with ethyl ether. The combined extracts were washed with water, dried over magnesium sulfate, filtered and evaporated under vacuum. The residue was chromatographed on silica, eluting with hexane/ethyl acetate (10:1) to give 271 mg (0.89 mmol,88%) of the product. FAB-MS: calculated for C19H15NO2 305: found 306 (M+H). 1H NMR (200 MHz,CDCl3): δ 2.28 (s,3H), 6.82 (d,2H), 7.19 (d,3H), 7.2-7.5 (m,5H), 8.05 (d,2H). | Cc1ccc(-c2ccccc2Oc2ccc([N+](=O)[O-])cc2)cc1 | null | 89 | null |
1,417,665 | ord_dataset-f8e6e6a2d2bf4135b9e346456c81700f | null | 2014-01-01T00:04:00 | true | [CH:1]1([N:6]2[C:15]3[N:14]=[C:13]([NH:16][C:17]4[CH:18]=[CH:19][C:20]([C:27]([O-:29])=[O:28])=[C:21]5[C:25]=4[O:24][CH:23]([CH3:26])[CH2:22]5)[N:12]=[CH:11][C:10]=3[N:9]([CH3:30])[C:8](=[O:31])[C@H:7]2[CH2:32][CH3:33])[CH2:5][CH2:4][CH2:3][CH2:2]1.[OH-].[Li+].Cl>CO.O1CCCC1>[CH:1]1([N:6]2[C:15]3[N:14]=[C:13]([NH:16][C:17]4[CH:18]=[CH:19][C:20]([C:27]([OH:29])=[O:28])=[C:21]5[C:25]=4[O:24][CH:23]([CH3:26])[CH2:22]5)[N:12]=[CH:11][C:10]=3[N:9]([CH3:30])[C:8](=[O:31])[C@H:7]2[CH2:32][CH3:33])[CH2:2][CH2:3][CH2:4][CH2:5]1 | CC[C@@H]1C(=O)N(C)c2cnc(Nc3ccc(C(=O)[O-])c4c3OC(C)C4)nc2N1C1CCCC1 | null | null | Cl | [Li+] | [OH-] | 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 | null | 12 | 7-[[(7R)-8-Cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2-methyl-2,3-dihydrobenzofuran-4-carboxylate 30c (100 mg, 0.21 mmol) and 1 M lithium hydroxide solution were dissolved in 50 mL of the mixture solvent of methanol and tetrahydrofuran (V/V=1:1). The reaction solution was stirred for 12 hours followed by the addition of 1 M hydrochloric acid to adjust pH to 6 to 7. The resulting solution was concentrated under reduced pressure. The residue was added dropwise with 1 M lithium hydroxide solution to adjust pH to 3 to 4 and extracted with ethyl acetate (30 mL×3). The combined organic phase was concentrated under reduced pressure to obtain the title compound 7-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2-methyl-2,3-dihydrobenzofuran-4-carboxylic acid 30d (90 mg, yield: 95.0%) as a white solid. | CC[C@@H]1C(=O)N(C)c2cnc(Nc3ccc(C(=O)O)c4c3OC(C)C4)nc2N1C1CCCC1 | null | 94.9 | null |
1,685,332 | ord_dataset-3953983e052a4076aa7cc0880b79cb8b | null | 2016-01-01T00:01:00 | true | [H-].[Na+].[I:3][C:4]1[CH:5]=[N:6][NH:7][CH:8]=1.Br[CH2:10][C:11]1[CH:16]=[CH:15][NH:14][C:13](=[O:17])[CH:12]=1>C1COCC1>[I:3][C:4]1[CH:5]=[N:6][N:7]([CH2:10][C:11]2[CH:16]=[CH:15][NH:14][C:13](=[O:17])[CH:12]=2)[CH:8]=1 | O=c1cc(CBr)cc[nH]1 | Ic1cn[nH]c1 | null | [H-] | [Na+] | 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 | 0.5 | Sodium hydride (19 mg, 0.48 mmol, 60 wt %) was added to a solution of 4-iodo-1H-pyrazole (47 mg, 0.24 mmol) in THF (2 mL) at 0° C. After 30 minutes, 4-(bromomethyl)pyridin-2(1H)-one (30 mg, 0.16 mmol) was added. The mixture was stirred at 25° C. for 12 hours. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (EtOAc/MeOH) to afford 4-((4-iodo-1H-pyrazol-1-yl)methyl)pyridin-2(1H)-one. MS ESI calc'd. for C9H9IN3O [M+H]+ 302. found 302. 1H NMR (400 MHz, DMSO-d6) δ 11.54 (s, 1H), 8.05 (s, 1H), 7.61 (s, 1H), 7.32 (d, J=6.8 Hz, 1H), 5.93-5.90 (m, 2H), 5.19 (s, 2H). | O=c1cc(Cn2cc(I)cn2)cc[nH]1 | null | null | null |
767,094 | ord_dataset-7a8649d55889427e85b208ae89475895 | null | 2007-01-01T00:04:00 | true | C(O[C:4](=[O:31])[CH2:5][O:6][C:7]1[CH:12]=[C:11]([CH:13]([CH3:15])[CH3:14])[CH:10]=[CH:9][C:8]=1[CH2:16][CH2:17][NH:18][S:19]([C:22]1[CH:27]=[C:26]([C:28]#[N:29])[CH:25]=[CH:24][C:23]=1[OH:30])(=[O:21])=[O:20])C.O.[NH2:33][NH2:34]>C(O)C>[C:28]([C:26]1[CH:25]=[CH:24][C:23]([OH:30])=[C:22]([S:19]([NH:18][CH2:17][CH2:16][C:8]2[CH:9]=[CH:10][C:11]([CH:13]([CH3:15])[CH3:14])=[CH:12][C:7]=2[O:6][CH2:5][C:4]([NH:33][NH2:34])=[O:31])(=[O:21])=[O:20])[CH:27]=1)#[N:29] | NN | CCOC(=O)COc1cc(C(C)C)ccc1CCNS(=O)(=O)c1cc(C#N)ccc1O | 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 | Ethyl[2-[2-(5-cyano-2-hydroxybenzenesulfonylamino)-ethyl]-5-isoproylphenoxy]acetate (0.266 g) was dissolved in 5 mL of ethanol. To the solution was added 0.087 mL of hydrazine monohydrate at room temperature, and the mixture was refluxed for 1 hour. The solvent was removed under reduced pressure to give 0.258 g of 5-cyano-N-[2-(2-hydrazinocarbonylmethoxy-4-isopropylphenyl)ethyl]-2-hydroxybenzenesulfonamide. | CC(C)c1ccc(CCNS(=O)(=O)c2cc(C#N)ccc2O)c(OCC(=O)NN)c1 | null | null | null |
1,409,472 | ord_dataset-7456bda2326f4bebaa874a5474d4cc0d | null | 2014-01-01T00:03:00 | true | [NH2:1][C:2]1[CH:6]=[CH:5][N:4]([C:7]2[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][CH:8]=2)[N:3]=1.C(O)(=O)C.[CH:19]1([CH:22]=O)[CH2:21][CH2:20]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH:19]1([CH2:22][NH:1][C:2]2[CH:6]=[CH:5][N:4]([C:7]3[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][CH:8]=3)[N:3]=2)[CH2:21][CH2:20]1 | N#Cc1ccc(-n2ccc(N)n2)cc1 | O=CC1CC1 | null | CC(=O)O[BH-](OC(C)=O)OC(C)=O | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCCl | CC(=O)O | null | null | null | null | null | null | null | null | null | null | null | Dissolve 4-(3-amino-pyrazol-1-yl)-benzonitrile (200 mg) in 1,2-dichloroethane (12 mL). Add acetic acid (0.36 mL) and cyclopropanecarboxaldehyde (0.08 mL, 1.06 mmol) and stir the mixture at room temperature under a nitrogen atmosphere for 40 min. Add sodium triacetoxyborohydride (674 mg, 3.18 mmol) and stir for 3 h at room temperature. Quench the reaction with water. Extract the mixture three timed with EtOAc. Dry the combined organic extracts over Na2SO4, filter and concentrate in vacuo to obtain the desired intermediate (136 mg, 54%) that was used without further purification. | N#Cc1ccc(-n2ccc(NCC3CC3)n2)cc1 | null | 53.8 | null |
84,006 | ord_dataset-7bed824f566d4af0b51d74d386b14bd6 | null | 1981-01-01T00:07:00 | true | [C:1]([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][CH2:18][CH2:19][NH:20][C:21]1[CH:31]=[CH:30][C:24]([C:25]([O:27]CC)=[O:26])=[CH:23][CH:22]=1)([O:3]C)=[O:2].[OH-].[K+].C(O)C.Cl>O>[C:1]([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][CH2:18][CH2:19][NH:20][C:21]1[CH:22]=[CH:23][C:24]([C:25]([OH:27])=[O:26])=[CH:30][CH:31]=1)([OH:3])=[O:2] | CCOC(=O)c1ccc(NCCCCCCCCCCCCCCCC(=O)OC)cc1 | null | null | Cl | [K+] | [OH-] | 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 | null | null | A solution of 8.8 g. of ethyl 4-(15-carbomethoxypentadecylamino)benzoate, 4.5 g. of potassium hydroxide, and 10 ml. of water in 90 ml. of ethanol is stirred at 75° for 10 hours, cooled, diluted with water, brought to pH 4 with dilute hydrochloric acid, and filtered. The solid is dried and crystallized from acetic acid to yield 4-(15-carboxypentadecylamino)benzoic acid as a white crystalline solid. | O=C(O)CCCCCCCCCCCCCCCNc1ccc(C(=O)O)cc1 | null | null | null |
1,214,798 | ord_dataset-dc3bb1b1ac4e4229a3fc28fb559a9777 | null | 2012-01-01T00:10:00 | true | [C@H:1]12[CH2:6][C@H:5]1[CH2:4][C@@H:3]([CH2:7][NH:8][C:9]([C:11]1[N:18]3[C:14]([S:15][CH:16]=[CH:17]3)=[N:13][C:12]=1[CH3:19])=[O:10])[NH:2]2.[F:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[S:31][C:30]([CH3:32])=[N:29][C:28]=2[C:33](O)=[O:34])=[CH:23][CH:22]=1>>[F:20][C:21]1[CH:22]=[CH:23][C:24]([C:27]2[S:31][C:30]([CH3:32])=[N:29][C:28]=2[C:33]([N:2]2[C@H:3]([CH2:7][NH:8][C:9]([C:11]3[N:18]4[C:14]([S:15][CH:16]=[CH:17]4)=[N:13][C:12]=3[CH3:19])=[O:10])[CH2:4][C@H:5]3[C@@H:1]2[CH2:6]3)=[O:34])=[CH:25][CH:26]=1 | Cc1nc2sccn2c1C(=O)NC[C@@H]1C[C@@H]2C[C@@H]2N1 | Cc1nc(C(=O)O)c(-c2ccc(F)cc2)s1 | 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 by reaction of 6-methyl-imidazo[2,1-b]thiazole-5-carboxylic acid [(1S,3S,5S)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide with 5-(4-fluoro-phenyl)-2-methyl-thiazole-4-carboxylic acid. LC-MS (basic): tR=1.29 min; [M+H]+=496.1. | Cc1nc(C(=O)N2[C@H](CNC(=O)c3c(C)nc4sccn34)C[C@@H]3C[C@@H]32)c(-c2ccc(F)cc2)s1 | null | null | null |
106,046 | ord_dataset-e7e9fe3dd42b4f499d5b17fe63bbf336 | null | 1983-01-01T00:06:00 | true | [OH:1][C:2]1[C:15]2[C@:14]34[CH2:16][CH2:17][N:18]([CH3:19])[C@@H:8]([C@@H:9]3[CH2:10][CH2:11][C:12](=[O:20])[CH2:13]4)[CH2:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.[C:21](OC(=O)C)(=[O:23])[CH3:22]>N1C=CC=CC=1>[C:21]([O:1][C:2]1[C:15]2[C@:14]34[CH2:16][CH2:17][N:18]([CH3:19])[C@@H:8]([C@@H:9]3[CH2:10][CH2:11][C:12](=[O:20])[CH2:13]4)[CH2:7][C:6]=2[CH:5]=[CH:4][CH:3]=1)(=[O:23])[CH3:22] | CC(=O)OC(C)=O | CN1CC[C@]23CC(=O)CC[C@H]2[C@H]1Cc1cccc(O)c13 | null | null | null | 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 | 25 | 8 | A mixture of (-)-4-hydroxy-N-methylmorphinan-6-one (500 mg, 1.84 mmol), acetic anhydride (5 ml), and pyridine (10 ml) was stirred at room temperature overnight. Acetic anhydride and pyridine were evaporated under vacuum and the residue was taken into toluene and evaporated again. The crude product was taken into CHCl3 and washed with H2O, dried and evaporated to give a foam which was recrystallized from iPr2O-hexane to afford (301 mg, 65%). An analytical sample was recrystallized from iPr2 : mp 96°-97°; [α]D26 -46.7° (c 1.126, CHCl3). | CC(=O)Oc1cccc2c1[C@]13CCN(C)[C@H](C2)[C@@H]1CCC(=O)C3 | null | null | null |
1,542,285 | ord_dataset-cac8df8aff894288876df4e093c9877f | null | 2015-01-01T00:02:00 | true | [NH:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]([O:8][CH3:9])=[O:7].[H-].[Na+].[F:12][CH2:13][CH2:14]I.O>CN(C=O)C>[F:12][CH2:13][CH2:14][N:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]([O:8][CH3:9])=[O:7] | COC(=O)c1ccc[nH]1 | FCCI | null | [H-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | 0.5 | Methyl 1H-pyrrole-2-carboxylate (3.0 g, 23.3 mmol) was solved in DMF (40 ml). Sodium hydride (1.40 g, 34.9 mmol, 60% in oil) was added and the mixture was stirred for 30 minutes at room-temperature. 1-Fluoro-2-iodoethane (4.1 g, 23.2 mmol) was added and the mixture was stirred for 15 h at 50° C. Water was added and the mixture was extracted with diethylether. The mixture was washed with saturated aqueous ammonium chloride. The product was purified chromatographically, using a mixture of petroleum and ethylacetate as eluent. Yield 1.1 g (28%). | COC(=O)c1cccn1CCF | null | null | null |
547,955 | ord_dataset-e967d076b4894c2c854795f019ed3c39 | null | 2002-01-01T00:06:00 | true | [O:1]=[C:2]([C:16]1[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=1)[CH:3]([CH2:9]N1CCCCC1)[CH2:4][C:5]([O:7][CH3:8])=[O:6]>C(O)C.Cl.O1CCOCC1>[N:18]1[CH:19]=[CH:20][CH:21]=[C:16]([C:2]([C:3](=[CH2:9])[CH2:4][C:5]([O:7][CH3:8])=[O:6])=[O:1])[CH:17]=1 | COC(=O)CC(CN1CCCCC1)C(=O)c1cccnc1 | null | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1COCCO1 | CCO | null | null | null | null | null | null | null | null | null | null | null | A solution of methyl 4-oxo-3-(piperidylmethyl)-4-(3-pyridyl)butanoate (4 g) in ethanol (10 mL) and 4N HCl/dioxane (4.0 mL) was heated at 80° C. for 12 hrs. The reaction mixture was concentrated and purified on flash chromatography (SIO2, CHCl3: MeOH: CH3COOH=10: 1:0.5) to give 2.28 g of the title compound. | C=C(CC(=O)OC)C(=O)c1cccnc1 | null | 80.7 | null |
390,476 | ord_dataset-44d518e567bd4c039d77233023f78bb2 | null | 1998-01-01T00:01:00 | true | [Li+].[CH3:2][CH:3]([N-]C(C)C)[CH3:4].[CH3:9][CH:10]([CH3:34])[CH2:11][C:12]1([CH2:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:13]1=[O:25].C(Br)C=C>C1COCC1>[CH3:9][CH:10]([CH3:34])[CH2:11][C:12]1([CH:26]([C:3]([CH3:4])=[CH2:2])[C:27]([O:29][C:30]([CH3:32])([CH3:31])[CH3:33])=[O:28])[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:13]1=[O:25] | CC(C)CC1(CC(=O)OC(C)(C)C)CCN(CCc2ccccc2)C1=O | CC(C)[N-]C(C)C | null | [Li+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | C=CCBr | null | null | null | null | null | null | null | null | null | -78 | 0.75 | LDA (2.0M, 7.7 mL, 16 mmol) is added to a solution of tert-butyl 3-(2-methylpropyl)-2-oxo-1-(2-phenylethyl)-3-pyrrolidineacetate (EXAMPLE 1, step 3; 4.62 g, 12.9 mmol) and THF (45 mL) at -78° C. The solution is stirred at -78° C. for 45 minutes and allyl bromide (1.3 mL, 16 mmol) is added. The solution is allowed to warm to 0° C. over 2 hours, and is allowed to stir overnight at room temperature. After quenching with saturated aqueous ammonium chloride, aqueous workup (EtOAc, MgSO4) and purification by column chromatography (2:1:17 v/v EtOAc:CH2Cl2 :hexane) gives 4.43 g (86%) of the title compound as yellow oil which solidified upon standing (mp 54.5°-56° C.). | C=C(C)C(C(=O)OC(C)(C)C)C1(CC(C)C)CCN(CCc2ccccc2)C1=O | null | 85.9 | null |
236,708 | ord_dataset-1acb071a357f438ea5993287375971cf | null | 1991-01-01T00:10:00 | true | C[O:2][C:3]1[CH:4]=[C:5]([CH:13]=[CH:14][C:15]=1[O:16]C)[C:6]([CH2:8][CH2:9][C:10]([OH:12])=[O:11])=[O:7].Br>>[OH:2][C:3]1[CH:4]=[C:5]([CH:13]=[CH:14][C:15]=1[OH:16])[C:6]([CH2:8][CH2:9][C:10]([OH:12])=[O:11])=[O:7] | COc1ccc(C(=O)CCC(=O)O)cc1OC | null | null | Br | 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 | A 5-carboxymethyl-4-(3,4-disubstituted phenyl)-2-mercaptothiazole derivative can be produced by reacting veratrole with succinic anhydride in the presence of anhydrous aluminum chloride to obtain 3-(3,4-dimethoxybenzoyl)propionic acid, subjecting the propionic acid to demethylation with hydrobromic acid to obtain 3-(3,4-dihydroxybenzoyl)propionic acid, then, subjecting it to enol-lactonation in the presence of acetic anhydride and sodium acetate, reacting the resulting compound sequentially with N-bromosuccinimide and with diphenyldiazomethane to obtain 3-(3,4-diacetoxybenzoyl)-3-bromopropionate, and reacting the propionate with ammonium dithiocarbamate to obtain the desired product. | O=C(O)CCC(=O)c1ccc(O)c(O)c1 | null | null | null |
977,375 | ord_dataset-f886e51ba1484c76a94bce1482f1eab9 | null | 2010-01-01T00:07:00 | true | [CH3:1][O:2][C:3]1[N:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][CH:7]=[C:6]2[N:13]1[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][N:21]2C(=O)C3C(=CC=CC=3)C2=O)[C:15](=[O:32])[CH2:14]1.O.NN>CCO>[NH2:21][CH2:20][CH2:19][N:16]1[CH2:17][CH2:18][N:13]([C:6]2[C:5]3[C:10](=[CH:11][CH:12]=[C:3]([O:2][CH3:1])[N:4]=3)[N:9]=[CH:8][CH:7]=2)[CH2:14][C:15]1=[O:32] | COc1ccc2nccc(N3CCN(CCN4C(=O)c5ccccc5C4=O)C(=O)C3)c2n1 | null | null | NN | 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 | 2 | To a solution of 2-(2-{4-[6-(methyloxy)-1,5-naphthyridin-4-yl]-2-oxo-1-piperazinyl}ethyl)-1H-isoindole-1,3(2H)-dione (100 mg, 0.232 mmol) in EtOH (2 mL) was added hydrazine hydrate (120 μL, 3.85 mmol). After 2 h at 85° C., the solution was concentrated and the residue purified by column chromatography (silica, 5-10% MeOH in DCM (1% NH4OH)) yielding the title compound (46 mg, 66%) as a yellow oil: LCMS (ES) m/e 302 (M+H)+. | COc1ccc2nccc(N3CCN(CCN)C(=O)C3)c2n1 | null | 65.8 | null |
781,538 | ord_dataset-8034115bd2ec4d3e95bd3ff7cfde0bde | null | 2007-01-01T00:07:00 | true | C(N(CC)CC)C.[NH2:8][C:9]1[CH:10]=[C:11]([C:23](=[O:25])[CH3:24])[CH:12]=[C:13]([C:19]([CH3:22])([CH3:21])[CH3:20])[C:14]=1[O:15][CH2:16][O:17][CH3:18].[C:26](Cl)(=[O:28])[CH3:27]>O1CCCC1>[C:23]([C:11]1[CH:12]=[C:13]([C:19]([CH3:20])([CH3:21])[CH3:22])[C:14]([O:15][CH2:16][O:17][CH3:18])=[C:9]([NH:8][C:26](=[O:28])[CH3:27])[CH:10]=1)(=[O:25])[CH3:24] | CC(=O)Cl | COCOc1c(N)cc(C(C)=O)cc1C(C)(C)C | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | CCN(CC)CC | null | null | null | null | null | null | null | null | null | null | 0.17 | Triethylamine (60 ml, 430 mmol) was added to a solution of the 1-[3-amino-5-(tert-butyl)-4-(methoxymethoxy)phenyl]-1-ethanone (53.9 g, 215 mmol) in tetrahydrofuran (270 ml) while cooling on ice under a nitrogen atmosphere and then acetyl chloride (23 ml, 323 mmol) was added dropwise. After stirring at the same temperature for 10 minutes, the mixture was stirred at room temperature for 30 minutes. The solvent was distilled off under reduced pressure, water was added to the residue and then extraction was performed with ethyl acetate. The organic layer was washed with 1 N hydrochloric acid water, water, saturated aqueous sodium hydrogencarbonate and brine in that order. After drying with anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure. The residue was recrystallized from ethyl acetate-hexane to yield the title compound (56.2 g, 89.3% yield) as light brown needle-like crystals. | COCOc1c(NC(C)=O)cc(C(C)=O)cc1C(C)(C)C | null | 89.1 | null |
611,560 | ord_dataset-5c4ee54447b84205a10f9c0473172972 | null | 2003-01-01T00:10:00 | true | [N+:1]([C:4]1[CH:5]=[C:6]([C:14](=[O:16])[CH3:15])[CH:7]=[C:8]([CH:13]=1)[C:9]([O:11][CH3:12])=[O:10])([O-:3])=[O:2].B.C1COCC1.C1COCC1>O>[N+:1]([C:4]1[CH:5]=[C:6]([CH:14]([OH:16])[CH3:15])[CH:7]=[C:8]([CH:13]=1)[C:9]([O:11][CH3:12])=[O:10])([O-:3])=[O:2] | COC(=O)c1cc(C(C)=O)cc([N+](=O)[O-])c1 | null | null | B | 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 | 25 | 24 | An oven-dried round bottom flask fitted with a magnetic stirring bar was charged with compound methyl 5-nitro-3-acetylbenzoate (0,5 g), prepared in step 1 of Intermediate 13, BH3THF (1 M solution in THF, 5 mol equiv.), and anhydrous THF. After stirring at room temperature for 24 h, H2O (20 mL) was added and the solution was concentrated in vacuo. The residue was taken in H2O (20 mL) and extracted with CHCl3 (3×100 mL). The combined CH2Cl2 extracts were washed with saturated Na2CO3 solution (20 mL), dried over Na2SO4 and filtered. The solvent was removed in vacuo to afford product. This was used in the next step without further purification. | COC(=O)c1cc(C(C)O)cc([N+](=O)[O-])c1 | null | null | null |
739,982 | ord_dataset-437aa6654d5044ddaef3346dc4c6e08a | null | 2006-01-01T00:11:00 | true | [CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([N:22]2[CH2:27][CH2:26][CH:25]([OH:28])[CH2:24][CH2:23]2)[N:9]([CH3:21])[C:10](=[O:20])[C:11]=1[O:12]CC1C=CC=CC=1)=[O:5])[CH3:2].[F:29][C:30]([F:35])([F:34])[C:31](O)=[O:32]>>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([N:22]2[CH2:27][CH2:26][CH:25]([O:28][C:31](=[O:32])[C:30]([F:35])([F:34])[F:29])[CH2:24][CH2:23]2)[N:9]([CH3:21])[C:10](=[O:20])[C:11]=1[OH:12])=[O:5])[CH3:2] | CCOC(=O)c1nc(N2CCC(O)CC2)n(C)c(=O)c1OCc1ccccc1 | O=C(O)C(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 | 10 | 5-Benzyloxy-2-(4-hydroxypiperidin-1-yl)-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxylic acid ethyl ester (0.760 g, 1.96 mmol) was treated with trifluroacetic acid (20 mL) at ambient temperature. After 10 h, the reaction mixture was concentrated and purified on silica gel column using 2–5% MeOH/CH2Cl2 to afford desired product as a brown paste (0.650 g, 84%). 1H NMR (500 MHz, CDCl3) δ: 10.02 (br s, 1H), 5.23–5.19 (m, 1H), 4.44 (q, J=7.0 Hz, 2H), 3.57 (s, 3H), 3.36–3.31 (m, 2H), 3.15–3.10 (m, 2H), 2.17–2.11 (m, 2H), 2.02–1.95 (m, 2H), 1.42 (t, J=7.0 Hz, 3H). LRMS (M+H) calcd for C15H19F3N3O6: 394.32. found: 394.09 | CCOC(=O)c1nc(N2CCC(OC(=O)C(F)(F)F)CC2)n(C)c(=O)c1O | null | null | null |
1,536,847 | ord_dataset-8d5c200bca27407ab9febe7598e16458 | null | 2015-01-01T00:01:00 | true | [Cl:1][C:2]1[C:10]([O:11][CH3:12])=[CH:9][C:5]([C:6](O)=[O:7])=[C:4]([C:13](=O)[C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20]#[N:21])[CH:15]=2)[CH:3]=1.O.[NH2:24][NH2:25]>CCO.O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:5]([C:6](=[O:7])[NH:24][N:25]=[C:13]2[C:14]2[CH:15]=[C:16]([CH:17]=[CH:18][CH:19]=2)[C:20]#[N:21])=[CH:9][C:10]=1[O:11][CH3:12] | COc1cc(C(=O)O)c(C(=O)c2cccc(C#N)c2)cc1Cl | NN | null | null | null | 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 | null | null | A solution of 4-chloro-2-(3-cyanobenzoyl)-5-methoxybenzoic acid (3.0 g, 9.50 mmol) in hydrazine hydrate (0.6 mL 11.4 mmol) and EtOH (40 mL) was heated at 80° C. for 2 h. The reaction mixture was diluted with water (100 mL), and the precipitate was filtered and dried to obtain 3-(7-chloro-6-methoxy-4-oxo-3,4-dihydrophthalazin-1-yl)benzonitrile (0.6 g, 17%) (312.4 [M+H]) 1H NMR: (400 MHz, DMSO) δ: 3.96 (s, 3H), 7.64 (s, 1H), 7.79-7.75 (t, 1H), 7.87 (s, 1H), 7.96-7.94 (d, J=8, 1H), 8.04-8.02 (d, J=8, 1H), 8.09 (s, 1H), 13.03 (s, 1H). | COc1cc2c(=O)[nH]nc(-c3cccc(C#N)c3)c2cc1Cl | null | 20.3 | null |
1,255,184 | ord_dataset-266f60b4555945d6afb2d2bdf5fa04e0 | null | 2013-01-01T00:02:00 | true | [C:1]1([C:7]2[CH:12]=[C:11]([C:13]3[N:17]4[CH:18]=[CH:19][C:20]([CH:22]5[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]5)=[CH:21][C:16]4=[N:15][CH:14]=3)[CH:10]=[CH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.[C:35](Cl)(=[O:37])[CH3:36].C([O-])(O)=O.[Na+]>C(Cl)Cl>[C:1]1([C:7]2[CH:12]=[C:11]([C:13]3[N:17]4[CH:18]=[CH:19][C:20]([CH:22]5[CH2:27][CH2:26][N:25]([C:35](=[O:37])[CH3:36])[CH2:24][CH2:23]5)=[CH:21][C:16]4=[N:15][CH:14]=3)[CH:10]=[CH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1 | CC(=O)Cl | c1ccc(-c2cc(-c3cnc4cc(C5CCNCC5)ccn34)ccn2)cc1 | null | O=C([O-])O | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | CCN(CC)CC | null | null | null | null | null | null | null | null | null | 25 | 2 | To a solution of 3-(2-phenyl-pyridin-4-yl)-7-piperidin-4-yl-imidazo[1,2-a]pyridine (Ex. 1.198) (1.0 eq, 0.20 mmol, 80 mg) in CH2Cl2 (2 ml) is added triethylamine (3 eq, 0.61 mmol, 0.09 ml) and acetyl chloride (1.5 eq, 0.31 mmol, 0.02 ml) and the reaction mixture is stirred at room temperature for 2 h. The reaction mixture is poured into NaHCO3 (50 ml) and the organic phase is extracted with CH2Cl2. The combined organic layers are washed with brine, dried over MgSO4, filtered and the solvent removed in vacuo. The reaction mixture is purified by flash column chromatography eluting with 9:1 DCM/MeOH to yield 1-{4-[3-(2-phenyl-pyridin-4-yl)-imidazo[1,2-a]pyridin-7-yl]-piperidin-1-yl}-ethanone as a white solid; [M+H]+=397 | CC(=O)N1CCC(c2ccn3c(-c4ccnc(-c5ccccc5)c4)cnc3c2)CC1 | null | null | null |
1,324,179 | ord_dataset-cfad8b3f00044bcda60a96b019f09872 | null | 2013-01-01T00:08:00 | true | [CH2:1]([O:3][C:4](=[O:20])[C:5]#[C:6][C:7]1[S:11][C:10]([NH:12]C(OC(C)(C)C)=O)=[N:9][CH:8]=1)[CH3:2].FC(F)(F)C(O)=O.C(=O)(O)[O-]>C(Cl)Cl>[CH2:1]([O:3][C:4](=[O:20])[C:5]#[C:6][C:7]1[S:11][C:10]([NH2:12])=[N:9][CH:8]=1)[CH3:2] | CCOC(=O)C#Cc1cnc(NC(=O)OC(C)(C)C)s1 | null | null | O=C([O-])O | 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 | 8 | (2-tert-Butoxycarbonylamino-thiazol-5-yl)-propynoic acid ethyl ester (1.2 g, 4.049 mmol) was dissolved in DCM (20 ml), trifluoroacetic acid (4.617 g, 40.93 mmol) was added in drop wise fashion at 0° C. After complete addition the reaction was allowed to stir for overnight at room temperature. Additional 3 ml of TFA was charged to the reaction and stirred for 2 hr. TLC showed complete reaction. Reaction was basified with sat. bicarbonate. The aqueous layer was extracted with ethyl acetate (30 ml×3). The combined organic layer was washed with water followed by brine and dried over anhydrous sodium sulfate and the solvent was removed on vacuo. The sticky solid product was obtained (0.700 g) | CCOC(=O)C#Cc1cnc(N)s1 | null | null | null |
517,856 | ord_dataset-a495451286334c5c9bbcbd48a00c1350 | null | 2001-01-01T00:09:00 | true | C[O:2][C:3]1[CH:4]=[CH:5][C:6]2[C:10]([C:11]([C:13]3[CH:18]=[CH:17][C:16]([O:19][CH2:20][O:21][C:22](=[O:24])[CH3:23])=[CH:15][CH:14]=3)=[O:12])=[C:9]([C:25]3[CH:30]=[CH:29][C:28]([O:31]C)=[CH:27][CH:26]=3)[S:8][C:7]=2[CH:33]=1.C(S)C.[Cl-].[Al+3].[Cl-].[Cl-]>>[OH:2][C:3]1[CH:4]=[CH:5][C:6]2[C:10]([C:11]([C:13]3[CH:14]=[CH:15][C:16]([O:19][CH2:20][O:21][C:22](=[O:24])[CH3:23])=[CH:17][CH:18]=3)=[O:12])=[C:9]([C:25]3[CH:26]=[CH:27][C:28]([OH:31])=[CH:29][CH:30]=3)[S:8][C:7]=2[CH:33]=1 | COc1ccc(-c2sc3cc(OC)ccc3c2C(=O)c2ccc(OCOC(C)=O)cc2)cc1 | null | null | [Al+3] | [Cl-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCS | null | null | null | null | null | null | null | null | null | null | null | null | [6-Methoxy-2-(4-methoxyphenyl)benzo[b]thiophen-3-yl][4-(Acetoxymethoxy)phenyl]methanone (1.7 g, 2.5 mmol) was converted to the title compound by the procedure of Example 3 using 500 mg (7.5 mmol) of ethanethiol and 1.0 g (7.5 mmol) of aluminum chloride except that the total reaction time was 4 hours. | CC(=O)OCOc1ccc(C(=O)c2c(-c3ccc(O)cc3)sc3cc(O)ccc23)cc1 | null | 29 | null |
857,571 | ord_dataset-faa0236be76c4501841c954527cd1b6c | null | 2008-01-01T00:12:00 | true | [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:12]([C:14]2[CH:19]=[C:18]([O:20][CH3:21])[C:17]([O:22][CH3:23])=[C:16]([O:24][CH3:25])[CH:15]=2)[OH:13])[CH:6]=[CH:7][C:8]=1[N+:9]([O-:11])=[O:10]>C(Cl)Cl.O=[Mn]=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:12]([C:14]2[CH:19]=[C:18]([O:20][CH3:21])[C:17]([O:22][CH3:23])=[C:16]([O:24][CH3:25])[CH:15]=2)=[O:13])[CH:6]=[CH:7][C:8]=1[N+:9]([O-:11])=[O:10] | COc1cc(C(O)c2cc(OC)c(OC)c(OC)c2)ccc1[N+](=O)[O-] | null | null | O=[Mn]=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 | 48 | A suspension of (3-methoxy-4-nitro-phenyl)-(3,4,5-trimethoxy-phenyl)-methanol (2.1 g, 6.1 mmol) and MnO2 (6.0 g, 69 mmol) in CH2Cl2 (100 mL) was stirred at room temperature for 2 days. The mixture was filtered through Celite and the filtrate was concentrated. The crude product was purified by flash chromatography (silica gel, Hexane:EtOAc 7:3) to afford (3-methoxy-4-nitro-phenyl)-(3,4,5-trimethoxy-phenyl)-methanone (1.0 g, 48%): 1H NMR (CDCl3) δ 7.90 (d, J=8 Hz, 1H), 7.50 (d, J=0 Hz, 1H), 7.37 (d, J=6 Hz, 1H), 7.05 (s, 2H), 4.02 (s, 3H), 3.96 (s, 3H), 3.88 (s, 6H). | COc1cc(C(=O)c2cc(OC)c(OC)c(OC)c2)ccc1[N+](=O)[O-] | null | 47.2 | null |
1,244,021 | ord_dataset-c544c0c663f54dbea4ddb52ddde7934e | null | 2013-01-01T00:01:00 | true | [CH3:1][N:2]1[CH2:6][CH2:5][CH:4]([NH2:7])[CH2:3]1.C(N(CC)C(C)C)(C)C.Cl[S:18]([C:21]1[CH:22]=[C:23]([C:27]2[C:36]([CH3:38])([CH3:37])[CH2:35][C:34]3[C:29](=[CH:30][CH:31]=[C:32]([C:39]([O:41][CH3:42])=[O:40])[CH:33]=3)[N:28]=2)[CH:24]=[CH:25][CH:26]=1)(=[O:20])=[O:19]>ClCCl>[CH3:37][C:36]1([CH3:38])[CH2:35][C:34]2[C:29](=[CH:30][CH:31]=[C:32]([C:39]([O:41][CH3:42])=[O:40])[CH:33]=2)[N:28]=[C:27]1[C:23]1[CH:24]=[CH:25][CH:26]=[C:21]([S:18](=[O:20])(=[O:19])[NH:7][CH:4]2[CH2:5][CH2:6][N:2]([CH3:1])[CH2:3]2)[CH:22]=1 | COC(=O)c1ccc2c(c1)CC(C)(C)C(c1cccc(S(=O)(=O)Cl)c1)=N2 | CN1CCC(N)C1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | CCN(C(C)C)C(C)C | null | null | null | null | null | null | null | null | null | 25 | 3 | To a stirred solution of 1-methylpyrrolidin-3-amine (52 mg, 0.52 mmol) and N,N-diisopropylethylamine (112 mg, 0.86 mmol) in dichloromethane (4 mL) was added methyl 2-(3-(chlorosulfonyl)phenyl)-3,3-dimethyl-3,4-dihydroquinoline-6-carboxylate (170 mg, 0.43 mmol) portionwise. The resultant yellow solution was stirred for 3 h at room temperature. The mixture was purified on preparative Thin layer chromatography to afford 152 mg of methyl 3,3-dimethyl-2-(3-(N-(1-methylpyrrolidin-3-yl)sulfamoyl)phenyl)-3,4-dihydroquinoline-6-carboxylate, which was used directly. | COC(=O)c1ccc2c(c1)CC(C)(C)C(c1cccc(S(=O)(=O)NC3CCN(C)C3)c1)=N2 | null | 77.6 | null |
1,361,296 | ord_dataset-d932d1d683704a8bad3d064bcb197acc | null | 2013-01-01T00:11:00 | true | [F:1][C:2]([C:5]1[O:9][C:8]([CH2:10][N:11]2[N:15]=[C:14]([NH2:16])[CH:13]=[N:12]2)=[CH:7][CH:6]=1)([F:4])[CH3:3].[C:17]1([C:23]2[O:27][CH:26]=[N:25][C:24]=2[C:28](O)=[O:29])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>>[F:4][C:2]([C:5]1[O:9][C:8]([CH2:10][N:11]2[N:15]=[C:14]([NH:16][C:28]([C:24]3[N:25]=[CH:26][O:27][C:23]=3[C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)=[O:29])[CH:13]=[N:12]2)=[CH:7][CH:6]=1)([F:1])[CH3:3] | CC(F)(F)c1ccc(Cn2ncc(N)n2)o1 | O=C(O)c1ncoc1-c1ccccc1 | 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 | Following general procedure Z2, starting from 2-[5-(1,1-difluoro-ethyl)-furan-2-ylmethyl]-2H-[1,2,3]triazol-4-ylamine and 5-phenyl-oxazole-4-carboxylic acid. | CC(F)(F)c1ccc(Cn2ncc(NC(=O)c3ncoc3-c3ccccc3)n2)o1 | null | null | null |
528,330 | ord_dataset-f027aa93238e424fbbf9bad1c7699adc | null | 2001-01-01T00:12:00 | true | [NH2:1][C:2]1[N:10]=[C:9]([SH:11])[N:8]=[C:7]2[C:3]=1[N:4]=[C:5]([OH:19])[N:6]2[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:26]([O:33][CH2:34]Cl)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>CN(C)C=O>[NH2:1][C:2]1[N:10]=[C:9]([S:11][CH2:34][O:33][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[N:8]=[C:7]2[C:3]=1[N:4]=[C:5]([OH:19])[N:6]2[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1 | ClCOCc1ccccc1 | Nc1nc(S)nc2c1nc(O)n2Cc1ccccc1 | null | O=C([O-])[O-] | [K+] | 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 | 25 | 4 | Crude 6-amino-9-benzyl-8-hydroxy-2-mercaptopurine (134 mg, 0.49 mmol) was suspended in dimethylformamide (60 ml). To the suspension were added potassium carbonate (100 mg, 0.72 mmol) and benzyloxymethyl chloride (0.1 ml, 0.7 mmol) in order. The mixture was stirred at room temperature for 4 hours. The solvent was removed in vacuo, and the residue was purified by silica gel chromatography (3% methanol/chloroform) to give the subject compound (90 mg, yield 47%). | Nc1nc(SCOCc2ccccc2)nc2c1nc(O)n2Cc1ccccc1 | null | 46.7 | null |
890,383 | ord_dataset-11068b1e475b4c5b82e56726ab0dddb7 | null | 2009-01-01T00:07:00 | true | [CH3:1][O:2][C:3](=[O:27])[CH:4]([C:9]1[CH:10]=[C:11]([C:16]2[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([F:26])[CH:17]=2)[CH:12]=[C:13]([OH:15])[CH:14]=1)[CH2:5][CH:6]([CH3:8])[CH3:7].[F:28][C:29]1[CH:30]=[C:31](B(O)O)[CH:32]=[C:33]([F:35])[CH:34]=1>>[CH3:1][O:2][C:3](=[O:27])[CH:4]([C:9]1[CH:10]=[C:11]([C:16]2[CH:21]=[C:20]([C:22]([F:24])([F:23])[F:25])[CH:19]=[C:18]([F:26])[CH:17]=2)[CH:12]=[C:13]([O:15][C:31]2[CH:30]=[C:29]([F:28])[CH:34]=[C:33]([F:35])[CH:32]=2)[CH:14]=1)[CH2:5][CH:6]([CH3:8])[CH3:7] | COC(=O)C(CC(C)C)c1cc(O)cc(-c2cc(F)cc(C(F)(F)F)c2)c1 | OB(O)c1cc(F)cc(F)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 in 83% yield from 2-(3′-fluoro-5-hydroxy-5′-trifluoromethyl-biphenyl-3-yl)-4-methyl-pentanoic acid methyl ester (prepared in Example B) and 3,5-difluorobenzene boronic acid under the conditions described in Example 15, step (g). | COC(=O)C(CC(C)C)c1cc(Oc2cc(F)cc(F)c2)cc(-c2cc(F)cc(C(F)(F)F)c2)c1 | null | 83 | null |
1,542,521 | ord_dataset-cac8df8aff894288876df4e093c9877f | null | 2015-01-01T00:02:00 | true | [OH:1][CH2:2][CH2:3][SH:4].[NH2:5][C:6]1[CH:11]=[N:10][C:9](Br)=[CH:8][N:7]=1>CN(C)C=O.O.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>[NH2:5][C:6]1[N:7]=[CH:8][C:9]([S:4][CH2:3][CH2:2][OH:1])=[N:10][CH:11]=1 | OCCS | Nc1cnc(Br)cn1 | 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 | CN(C)C=O | null | null | null | null | null | null | null | null | null | 120 | 3 | According to the method described in WO2004/052869, 2-hydroxy-1-ethanethiol (0.93 mL) and tetrakis(triphenylphosphine)palladium (3.39 g) were added to a solution of 2-amino-5-bromopyrazine (1.00 g, 5.75 mmol) in N,N-dimethylformamide (15.1 mL), and the mixture was heated and stirred at 120° C. in a sealed tube for about 3 hours. After cooling, the reaction mixture was diluted with water and extracted with a mixed solution (dichloromethane:ethanol=5:1) (100 mL×6). The organic layer was dried over anhydrous sodium sulfate and then filtrated, and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (hexane:ethyl acetate=1:1, then ethyl acetate, and then ethyl acetate:methanol=10:1) and was recrystallized (using chloroform) to give the title compound as yellow needle crystals (470 mg, yield: 44%). | Nc1cnc(SCCO)cn1 | null | null | null |
684,811 | ord_dataset-359b8fc87f4244be89d6f02bc5036eac | null | 2005-01-01T00:09:00 | true | [F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][S:10][C:11]1[N:16]=[C:15]([NH2:17])[C:14]([NH2:18])=[C:13]([NH2:19])[N:12]=1.[C:20](OCC)(=O)[CH:21]=[O:22].O.Cl>[Na].CO>[NH2:17][C:15]1[C:14]2[N:18]=[CH:20][C:21](=[O:22])[NH:19][C:13]=2[N:12]=[C:11]([S:10][CH2:9][C:3]2[CH:4]=[CH:5][CH:6]=[C:7]([F:8])[C:2]=2[F:1])[N:16]=1 | Nc1nc(SCc2cccc(F)c2F)nc(N)c1N | CCOC(=O)C=O | null | Cl | [Na] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | O | null | null | null | null | null | null | null | null | null | 25 | 0.25 | The product of example 2, step (c) (100 mg) was dissolved in a solution of sodium (0.05 g) in methanol (5 ml). This was left to stir for 15 min at room temperature, then ethyl glyoxalate (134 μl) was added to the mixture which was left to stir for 12 hr at room temperature. Water (5 ml) was added, then concentrated hydrochloric acid was slowly .5 added to acidify the solution to ˜pH5 whereupon a solid precipitated which was isolated by filtration and dried over P2O5 at 50° C. to yield a pale yellow solid (44.5 mg). | Nc1nc(SCc2cccc(F)c2F)nc2[nH]c(=O)cnc12 | null | null | null |
1,582,960 | ord_dataset-380e279f82154dba9e08ab51b3bdd08a | null | 2015-01-01T00:05:00 | true | [NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[CH:10]=2)[C:6]=1[C:7]#[N:8].[C:16]([O:22][CH2:23][CH3:24])(=[O:21])[CH2:17][C:18]([CH3:20])=O.Cl[Sn](Cl)(Cl)Cl>C1(C)C=CC=CC=1>[NH2:8][C:7]1[C:17]([C:16]([O:22][CH2:23][CH3:24])=[O:21])=[C:18]([CH3:20])[N:1]=[C:2]2[S:3][CH:4]=[C:5]([C:9]3[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[CH:10]=3)[C:6]=12 | Cc1cccc(-c2csc(N)c2C#N)c1 | CCOC(=O)CC(C)=O | null | Cl[Sn](Cl)(Cl)Cl | 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 | To a stirred solution of 2-amino-4-(3-methylphenyl)-3-thiophenecarbonitrile (Description 56) (2.98 g, 13.91 mmol) in toluene (75 mL) at RT was added ethyl acetoacetate (1.76 mL, 13.91 mmol) and SnCl4 (3.26 mL, 27.8 mmol). The reaction mixture was refluxed under a nitrogen atmosphere for ca. 4 h and was then cooled to RT and concentrated in vacuo. The residue was re-partitioned between ethyl acetate and water (ca. 80 mL each) and the aqueous layer separated and re-extracted with ethyl acetate (ca. 50 mL×2). The combined organic layer was then passed though a phase separator and the solvent removed in vacuo. The residue was purified by chromatography on silica, eluting with a gradient of 0-50% ethyl acetate in cyclohexane, to give the title compound (880 mg). LCMS (A) m/z: 327 [M+1]+, Rt 1.23 min (acidic). | CCOC(=O)c1c(C)nc2scc(-c3cccc(C)c3)c2c1N | null | 19.4 | null |
214,126 | ord_dataset-b67d30cd146f49dcbf24faee022f1a09 | null | 1990-01-01T00:08:00 | true | [Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12][C:13](=O)[CH3:14])=[CH:8][CH:7]=1.C([O-])(=O)C.[NH4+].C([BH3-])#[N:22].[Na+]>CO>[Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12][CH:13]([NH2:22])[CH3:14])=[CH:8][CH:7]=1 | CC(=O)Cc1ccc(OCCCCl)cc1 | [BH3-]C#N | null | CC(=O)[O-] | [NH4+] | [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 | null | 5 | A 1.36 g sample of 4-(3-chloropropoxy)phenylacetone, prepared above, was dissolved in 200 mL of methanol. To this was added 7.71 g of ammonium acetate followed by 0.76 g sodium cyanoborohydride with stirring. After 5 hours, the solvent was evaporated in vacuo, the residue was dissolved in 150 mL diethylether and 200 ml of 1 N hydrochloric acid solution. The aqueous phase was separated and washed with a second portion of diethylether, basified to a pH of 10-12 with 6 N sodium hydroxide, and extracted with three, 100 mL portions of diethylether. The basic ether extracts were | CC(N)Cc1ccc(OCCCCl)cc1 | null | null | null |
1,226,646 | ord_dataset-cde802cdb7434a5f82a22981ccaefc4e | null | 2012-01-01T00:11:00 | true | [Cl:1][C:2]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14](=[O:17])[N:13]([CH2:18][CH2:19][O:20][C:21]3[C:30]4[C:25](=[CH:26][C:27]([O:31][CH3:32])=[CH:28][CH:29]=4)[N:24]=[CH:23][CH:22]=3)[N:12]=2)[CH:8]=[CH:7][C:3]=1[C:4]([NH2:6])=O.N1C=CC=CC=1.S(Cl)(Cl)=O>>[Cl:1][C:2]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14](=[O:17])[N:13]([CH2:18][CH2:19][O:20][C:21]3[C:30]4[C:25](=[CH:26][C:27]([O:31][CH3:32])=[CH:28][CH:29]=4)[N:24]=[CH:23][CH:22]=3)[N:12]=2)[CH:8]=[CH:7][C:3]=1[C:4]#[N:6] | COc1ccc2c(OCCn3nc(-c4ccc(C(N)=O)c(Cl)c4)ccc3=O)ccnc2c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O=S(Cl)Cl | c1ccncc1 | null | null | null | null | null | null | null | null | null | 23 | 18 | See example 75 for a general synthesis. To a solution of 2-chloro-4-(1-(2-(7-methoxyquinolin-4-yloxy)ethyl)-6-oxo-1,6-dihydropyridazin-3-yl)benzamide (120 mg, 266 μmol) in pyridine (10763 μL, 133075 μmol) was added thionyl chloride (194 μL, 2661 μmol). The reaction was then stirred overnight at 23° C. for 18 hours. The reaction was then chilled to 0° C., and quenched with sat. NH4Cl. The organic contents were extracted with DCM (30 mL), separated, dried over MgSO4, then concentrated to a solid under reduced pressure. The product was then purified on silica (12 g) eluting with 3>5% of NH3 in MeOH/DCM and isolated as an off white solid. MS (ESI pos. ion) m/z: (MH+); calc'd for C23H17ClN4O3: 432. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 3.92 (s, 3 H) 4.67 (t, J=5.02 Hz, 2 H) 4.81 (t, J=5.27 Hz, 2 H) 6.65 (d, J=5.52 Hz, 1 H) 6.99 (dd, J=9.29, 2.26 Hz, 1 H) 7.09 (d, J=9.54 Hz, 1 H) 7.30 (s, 1 H) 7.65 (d, J=9.54 Hz, 2 H) 7.68-7.74 (m, 1 H) 7.87 (s, 1 H) 7.95 (d, J=9.54 Hz, 1 H) 8.64 (d, J=5.02 Hz, 1 H). | COc1ccc2c(OCCn3nc(-c4ccc(C#N)c(Cl)c4)ccc3=O)ccnc2c1 | null | null | null |
1,086,834 | ord_dataset-52a37d876ddb453e86de0c15fa233d29 | null | 2011-01-01T00:09:00 | true | C(N(CC)CC)C.Cl.[CH3:9][O:10][C:11](=[O:24])[C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH2:18][NH2:19])[C:13]=1[C:20]([O:22][CH3:23])=[O:21].[C:25](Cl)(=[O:27])[CH3:26]>ClCCl>[CH3:9][O:10][C:11](=[O:24])[C:12]1[C:13](=[C:14]([CH2:18][NH:19][C:25](=[O:27])[CH3:26])[CH:15]=[CH:16][CH:17]=1)[C:20]([O:22][CH3:23])=[O:21] | CC(=O)Cl | COC(=O)c1cccc(CN)c1C(=O)OC | null | Cl | 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 | 4 | null | Triethylamine (1.87 g, 18 mmol) was added slowly to a stirred suspension of methyl-3-(aminomethyl)-2-(methoxycarbonyl)benzoate hydrochloride (2.0 g, 8 mmol) in dichloromethane (30 ml). The resulting mixture was cooled in an ice bath to 4° C. Acetyl chloride (0.73 g, 9 mmol) was added dropwise at a rate such that the temperature stayed between 4-7° C. After addition was complete, the mixture was stirred in the ice bath for an additional 30 minutes and then allowed to warm to room temperature and maintained for 2 hours. The reaction mixture was washed with water (2×30 ml), brine (30 ml) and dried. Solvent was removed in vacuo and the product was purified by chromatography (dichloromethane/ethyl acetate 6 to 4) to afford 1.65 g (80%) of the product as an oil: 1H NMR (CDCl3) δ 7.86 (d, J=7.7 Hz, 1H), 7.62 (d, J=7.6 Hz); 7.46 (t, J=7.7 Hz); 6.29 (b, 1H), 4.39 (d, J=6.1 Hz, 2H), 3.93 (s, 3H), 3.90 (s, 3H), 1.96 (s, 3H). | COC(=O)c1cccc(CNC(C)=O)c1C(=O)OC | null | 77.8 | null |
285,273 | ord_dataset-d63ab258f4634f87bdebbaff0a341c28 | null | 1994-01-01T00:02:00 | true | [N+]([O-])(O)=[O:2].[CH3:5][C:6]1([CH3:15])[CH2:11][CH2:10][CH2:9][C@@H:8]([CH3:12])[C@@H:7]1[CH:13]=[O:14]>>[CH3:15][C:6]1([CH3:5])[CH2:11][CH2:10][CH2:9][C@@H:8]([CH3:12])[C@@H:7]1[C:13]([OH:2])=[O:14] | C[C@@H]1CCCC(C)(C)[C@H]1C=O | O=[N+]([O-])O | 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 | 55 | 2 | In a 300-ml 4-necked flask equipped with a condenser, a thermometer, a dropping funnel, and a stirrer was placed 38 g of nitric acid (aqueous 60% solution) and heated to 55° C. Then, 90 g of (1S,6R)-2,2,6-trimethylcyclohexanecarbaldehyde (14) [composition: 91% of the (1S,6R)-form, 9% of the (1R,6R)-form] synthesized in Synthesis Example 5-A) was added dropwise thereto with stirring over a period of 2 hours. After carrying out the reaction for 3 hours at the same temperature, the reaction mixture was washed with water with 90 g of toluene and 100 g of water at room temperature, followed by separating an organic layer formed from an aqueous layer. The organic layer was washed thrice with 100 g of a saturated aqueous sodium chloride solution, followed by separating the organic layer from an aqueous layer. The toluene was distilled off from an organic layer by an evaporator under reduced pressure to provide 98 g of crude (1S,6R)-2,2,6-trimethylcyclohexanecarboxylic acid (15) [composition: 91% of the (1S,6R)-form, 9% of the (1R,6R)-form]. The product was recrystallized from methylene chloride as a solvent to provide 46 g of pure (1S,6R)-2,2,6-trimethylcyclohexanecarboxylic acid (15) [melting point: 67° C. to 68° C.; optical rotation; [α]D25 =-14.40°]. | C[C@@H]1CCCC(C)(C)[C@H]1C(=O)O | null | 98.7 | null |
907,571 | ord_dataset-46d216f2c4374ef5b9df90427e2a4cd4 | null | 2009-01-01T00:09:00 | true | [CH3:1][NH:2][CH3:3].[Cl:4][C:5]1[CH:13]=[CH:12][C:8]([C:9](O)=[O:10])=[CH:7][N:6]=1>>[Cl:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]([N:2]([CH3:3])[CH3:1])=[O:10])=[CH:7][N:6]=1 | CNC | O=C(O)c1ccc(Cl)nc1 | 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 (D36) was prepared from dimethylamine and 6-chloronicotinic acid according to the procedure described for Description 35. MS electrospray (+ve ion) 185 (MH+). | CN(C)C(=O)c1ccc(Cl)nc1 | null | null | null |
1,514,733 | ord_dataset-8c74302143c04eb9983e4b3a7ead2d72 | null | 2014-01-01T00:12:00 | true | [CH2:1](Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:9]1([C:15]2[NH:19][N:18]=[C:17]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH:16]=2)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O>[CH2:1]([N:19]1[C:15]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:16][C:17]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[N:18]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1 | BrCc1ccccc1 | CCOC(=O)c1cc(-c2ccccc2)[nH]n1 | null | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | O | null | null | null | null | null | null | null | null | null | null | null | Benzyl bromide (696 mg, 4.01 mmol) was added to ethyl 5-phenyl-1H-pyrazole-3-carboxylate (880 mg, 4.1 mmol) and potassium carbonate (562 mg, 4.01) in DMF (8 mL). The reaction was stirred for several h and then diluted with water. The mixture was washed several times with ethyl acetate and the combine extracts were dried over sodium sulfate. The solvent was removed under reduced pressure and the residue was purified on ISCO using 0-100% ethyl acetate/hexane gradient to give ethyl 1-benzyl-5-phenyl-1H-pyrazole-3-carboxylate (1.3 g, quantitative). MS (ESI) m/z: Calculated for C19H18N2O2: 306.14. found: 307.1 (M+H)+. | CCOC(=O)c1cc(-c2ccccc2)n(Cc2ccccc2)n1 | null | 105.8 | null |
362,280 | ord_dataset-0b24d1f58a024ed7bc2bda95b2430c72 | null | 1997-01-01T00:04:00 | true | C([NH:4][C:5]1[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[C:7]([C:15]([F:18])([F:17])[F:16])[C:6]=1[N+:19]([O-:21])=[O:20])(=O)C>Cl.CCO>[N+:19]([C:6]1[C:7]([C:15]([F:16])([F:17])[F:18])=[CH:8][C:9]([C:11]([F:12])([F:13])[F:14])=[CH:10][C:5]=1[NH2:4])([O-:21])=[O:20] | CC(=O)Nc1cc(C(F)(F)F)cc(C(F)(F)F)c1[N+](=O)[O-] | null | null | Cl | 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 | null | A mixture of 1-acetamido-2-nitro-3,5-bis(trifluoromethyl)benzene (200 mg, 0.63 mmol) in concentrated HCl (3 mL) and EtOH (3 mL) was refluxed overnight, then it was extracted by ethyl acetate (2×3 mL). The extract was dried over Mg2SO4 and evaporated to give 2-nitro-3,5-bis(trifluoromethyl)aniline 123 mg (71%). 1H NMR (DMSO-d6): δ6.392 (s, 2H), 7.131 (s, 1H), 7.375 (s, 1H). | Nc1cc(C(F)(F)F)cc(C(F)(F)F)c1[N+](=O)[O-] | null | 71.2 | null |
1,673,857 | ord_dataset-9cc455db05a444779921f786a45b21a6 | null | 2015-01-01T00:12:00 | true | [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9](=O)[CH:8]([NH:14][C:15]([C:17]1[O:21][N:20]=[C:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:18]=1[C:28]([F:31])([F:30])[F:29])=O)[CH2:7][CH2:6]2.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:41])=CC=1>C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]1[S:41][C:15]([C:17]3[O:21][N:20]=[C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[C:18]=3[C:28]([F:31])([F:30])[F:29])=[N:14][C:8]=1[CH2:7][CH2:6]2 | COc1ccc2c(c1)CCC(NC(=O)c1onc(-c3ccccc3)c1C(F)(F)F)C2=O | 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 | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | 140 | null | A mixture of N-(6-methoxy-1-oxo-1,2,3,4-tetrahydronaphthalen-2-yl)-3-phenyl-4-(trifluoromethyl)isoxazole-5-carboxamide (Preparation 56A, 337 mg, 0.783 mmol) and Lawesson's reagent (2,4-Bis-[4-methoxyphenyl]-1,3-dithia-2,4-diphosphetane 2,4-disulfide) (475 mg, 1.175 mmol) in THF (4.0 ml) was heated for 33 min at 140° C. on a microwave which resulted in an incomplete reaction. The reaction mixture was then microwaved for 15 min more at 140° C. The crude reaction mixture was loaded onto a 40 g silica gel Redisep® cartridge which was presaturated with 10% EtOAc-hexanes and eluted with the same. The 5-(7-methoxy-4,5-dihydronaphtho[2,1-d]thiazol-2-yl)-3-phenyl-4-(trifluoromethyl)isoxazole (0.365 g, 0.852 mmol, quant. yield) was isolated as a yellow solid. The product had an LC ret. time=2.62 min. (condition: Start % B=0; Final % B=100; Gradient Time=2 min; Flow Rate=5 ml/min; Wavelength=220; Solvent Pair=MeOH/H2O/TFA; Solvent A=0.1% TFA in MeOH: H2O (10:90); Solvent B=0.1% TFA in; MeOH: H2O (10:90); Column 1=Waters Sunfire C18 5 um 4.6×30 mm); LC/MS M+1=429.04. | COc1ccc2c(c1)CCc1nc(-c3onc(-c4ccccc4)c3C(F)(F)F)sc1-2 | null | 108.8 | null |
1,393,148 | ord_dataset-12dc3bd21bcf44d09e5b4249afe15161 | null | 2014-01-01T00:02:00 | true | [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:14]([NH:16]C(=O)OCC2C=CC=CC=2)[CH3:15])[CH:6]=[CH:7][C:8]=1[NH:9][S:10]([CH3:13])(=[O:12])=[O:11].C(N)C>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:14]([NH2:16])[CH3:15])[CH:6]=[CH:7][C:8]=1[NH:9][S:10]([CH3:13])(=[O:12])=[O:11] | COc1cc(C(C)NC(=O)OCc2ccccc2)ccc1NS(C)(=O)=O | null | null | CCN | 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 | Through similar procedure to that in Example 1-2 excepting using Benzyl N-{1-[3-methoxy-4-(methylsulfonylamino)phenyl]ethyl}carbamate (14-1) as a starting material, □1□3-Methoxy-4-(methylsulfonylamino)phenyl]ethyl amine (14-3, CHK-570) having following physicochemical properties was synthesized: | COc1cc(C(C)N)ccc1NS(C)(=O)=O | null | null | null |
225,796 | ord_dataset-67612e25ea9d4b29966a776893a43d59 | null | 1991-01-01T00:04:00 | true | [NH2:1][CH:2]1[N:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[F:15])[C:6]2[CH:16]=[CH:17][CH:18]=[CH:19][C:5]=2[NH:4][C:3]1=[O:20].[C:21](Cl)(=[O:30])[CH:22]=[CH:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(N(CC)CC)C>C(Cl)Cl>[C:21]([NH:1][CH:2]1[N:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[F:15])[C:6]2[CH:16]=[CH:17][CH:18]=[CH:19][C:5]=2[NH:4][C:3]1=[O:20])(=[O:30])[CH:22]=[CH:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1 | O=C(Cl)C=Cc1ccccc1 | NC1N=C(c2ccccc2F)c2ccccc2NC1=O | 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 | null | 16 | 3-(RS)-Amino-1,3-dihydro-5-(2'-fluorophenyl)-2H-1,4-benzodiazepin-2-one (50 mg, 0.186 mmol) was suspended in methylene chloride (1 ml). Cinnamoyl chloride (34.5 mg, 0.207 mol) was added to the methylene chloride mixture. The pH of the stirred mixture was adjusted to ~9 with 50 μl of triethylamine. After stirring for 16 hours the mixture was filtered. The product in the filtrate was purified by prep TLC. The product band was collected by washing the silica containing the product, with 80:20:2 CMW. The solvent was evaporated and the residue was dissolved in methanol, placed in a small vial and evaporated. Yield 16.6 mg. | O=C(C=Cc1ccccc1)NC1N=C(c2ccccc2F)c2ccccc2NC1=O | null | null | null |
1,310,455 | ord_dataset-2d6edb8ffd434003bb508360153bd9bb | null | 2013-01-01T00:07:00 | true | C(N(CC)CC)C.[NH2:8][C:9]1[C:18]2[N:19]=[C:20]([CH2:31][O:32][CH2:33][CH3:34])[N:21]([CH2:22][C:23]([NH:26][S:27]([CH3:30])(=[O:29])=[O:28])([CH3:25])[CH3:24])[C:17]=2[C:16]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[N:10]=1.Cl[C:36]([O:38][CH2:39][CH2:40][CH3:41])=[O:37]>ClCCl>[CH2:33]([O:32][CH2:31][C:20]1[N:21]([CH2:22][C:23]([CH3:25])([NH:26][S:27]([CH3:30])(=[O:29])=[O:28])[CH3:24])[C:17]2[C:16]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[N:10]=[C:9]([NH:8][C:36](=[O:37])[O:38][CH2:39][CH2:40][CH3:41])[C:18]=2[N:19]=1)[CH3:34] | CCOCc1nc2c(N)nc3ccccc3c2n1CC(C)(C)NS(C)(=O)=O | CCCOC(=O)Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | CCN(CC)CC | null | null | null | null | null | null | null | null | null | 0 | 24 | Triethylamine (2.67 mL, 5 eq) was added to a chilled (ice/water bath) suspension of N-{2-[4-amino-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-yl]-1,1-dimethylethyl}methanesulfonamide (1.5 g, 1 eq) in dichloromethane (150 mL). A solution of propyl chloroformate (1.55 g, 3.3 eq) in dichloromethane (5 mL) was added dropwise to give a clear solution. The reaction mixture was allowed to come to ambient temperature with stirring for 24 hours. The reaction mixture was washed sequentially with water (150 mL), 4% sodium carbonate (150 mL), water (150 mL), and brine (150 mL). The organic layer was concentrated under reduced pressure. The residue was purified by automated flash chromatography (silica gel eluted with a linear gradient of 0-20% CMA in chloroform, 1500 mL) followed by recrystallization from diethyl ether to provide 1.23 g of propyl 2-ethoxymethyl-1-{2-methyl-2-[(methylsulfonyl)amino]propyl}-1H-imidazo[4,5-c]quinolin-4-ylcarbamate as a white powder, mp 177-179° C. Anal calcd for C22H31N5O5S: C, 55.33; H, 6.54; N, 14.66. Found: C, 55.41; H, 6.47; N, 14.45. | CCCOC(=O)Nc1nc2ccccc2c2c1nc(COCC)n2CC(C)(C)NS(C)(=O)=O | null | 67.2 | null |
1,709,415 | ord_dataset-3f2a531ffbae4b9eb1048afcd7953beb | null | 2016-01-01T00:04:00 | true | [CH3:1][C:2]1[NH:6][C:5]2[CH:7]=[CH:8][CH:9]=[CH:10][C:4]=2[N:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:18][CH2:19][OH:20]>CN(C=O)C.CCOC(C)=O>[CH3:1][C:2]1[N:6]([CH2:18][CH2:19][OH:20])[C:5]2[CH:7]=[CH:8][CH:9]=[CH:10][C:4]=2[N:3]=1 | Cc1nc2ccccc2[nH]1 | OCCBr | null | O=C([O-])[O-] | [Cs+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOC(C)=O | CN(C)C=O | null | null | null | null | null | null | null | null | null | 150 | 1 | To a solution of 2-methyl-1H-benzimidazole (3.50 g, 25.95 mmol) in DMF (70.0 mL), Cs2CO3 (12.08 g, 36.33 mmol) and 2-bromoethanol (2.5 mL, 34.15 mmol) was added. After stirring at 150° C. for 1 h, the reaction mixture was allowed to reach rt and was diluted with EtOAc. The org. layer was separated and the aq. layer was extracted with EtOAc (5×). The combined org. layers were washed with brine, dried (MgSO4), filtered and the solvent was removed under reduced pressure to yield 2-(2-methyl-1H-benzoimidazol-1-yl)ethanol which was used in the next step without further purification. LC-MS conditions B: tR=0.25 min, [M+H]+=177.17. | Cc1nc2ccccc2n1CCO | null | null | null |
102,932 | ord_dataset-bdb961f26fac426eaa2de8f54a284acf | null | 1983-01-01T00:02:00 | true | [OH:1][N:2]=[C:3]([C:9](=[O:11])[CH3:10])[C:4]([O:6][CH2:7][CH3:8])=[O:5].[Cl:12][C:13]1[CH:20]=[C:19]([Cl:21])[CH:18]=[CH:17][C:14]=1[CH2:15]Cl.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>C(OCC)(=O)C>[Cl:12][C:13]1[CH:20]=[C:19]([Cl:21])[CH:18]=[CH:17][C:14]=1[CH2:15][O:1][N:2]=[C:3]([C:9](=[O:11])[CH3:10])[C:4]([O:6][CH2:7][CH3:8])=[O:5] | CCOC(=O)C(=NO)C(C)=O | ClCc1ccc(Cl)cc1Cl | null | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | CCOC(C)=O | null | null | null | null | null | null | null | null | null | null | null | Ethyl 2-hydroxyimino-3-oxobutyrate (syn isomer, 17.0 g.), 2,4-dichlorobenzyl chloride (25 g.), potassium carbonate (22.0 g.), N,N-dimethylformamide (25 ml.) and ethyl acetate (25 ml.) were treated in a similar manner to that of Example A-(1) to give ethyl 2-(2,4-dichlorobenzyloxyimino)-3-oxobutyrate (syn isomer, 33.7 g.) | CCOC(=O)C(=NOCc1ccc(Cl)cc1Cl)C(C)=O | null | 99.2 | null |
1,182,019 | ord_dataset-9cd817a75dfc4fe7ad19d4232772d5ff | null | 2012-01-01T00:07:00 | true | [CH3:1][C:2]12[CH2:14][C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[CH:3]1[NH:4][CH2:5][CH2:6][CH2:7]2.[C:15](O)(=O)[CH3:16].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>ClCCCl>[CH2:15]([N:4]1[CH2:5][CH2:6][CH2:7][C:2]2([CH3:1])[CH2:14][C:13]3[C:8]([CH:3]12)=[CH:9][CH:10]=[CH:11][CH:12]=3)[CH3:16] | CC(=O)O | CC12CCCNC1c1ccccc1C2 | null | CC(=O)O[BH-](OC(C)=O)OC(C)=O | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCCl | null | null | null | null | null | null | null | null | null | null | 70 | 3 | To a solution of (4aRS,9bRS)-4a-methyl-2,3,4,4a,5,9b-hexahydro-1H-indeno[1,2-b]pyridine (140 mg) in 1,2-dichloroethane (3 ml) were added acetic acid (0.214 ml) and sodium triacetoxyborohydride (1.1 g), followed by heating and stirring at 70° C. for 3 hours. The reaction solution was basified by adding a 1 M aqueous sodium hydroxide solution, extracted with chloroform, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to obtain (4aRS,9bRS)-1-ethyl-4a-methyl-2,3,4,4a,5,9b-hexahydro-1H-indeno[1,2-b]pyridine (105 mg) as an oily substance. This was made into a hydrochloride by a conventional method, washed with ethyl acetate, and collected by filtration to obtain (4aRS,9bRS)-1-ethyl-4a-methyl-2,3,4,4a,5,9b-hexahydro-1H-indeno[1,2-b]pyridine hydrochloride (108 mg) as a colorless powder. | CCN1CCCC2(C)Cc3ccccc3C12 | null | null | null |
459,136 | ord_dataset-aa5bc55d09b7465ab353e144a7ac3ad1 | null | 2000-01-01T00:03:00 | true | C(=O)([O-])[O-].[K+].[K+].[CH3:7][O:8][C:9]1[S:13][C:12](=[O:14])[NH:11][N:10]=1.Cl[CH2:16][C:17](=[O:19])[CH3:18]>O1CCOCC1>[CH3:7][O:8][C:9]1[S:13][C:12](=[O:14])[N:11]([CH2:16][C:17](=[O:19])[CH3:18])[N:10]=1 | CC(=O)CCl | COc1n[nH]c(=O)s1 | null | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1COCCO1 | null | null | null | null | null | null | null | null | null | null | null | 20 | 69 g of potassium carbonate are added to a solution of 33 g of 5-methoxy-3H-[1,3,4]thiadiazol-2-one in 400 ml of dioxane and the reaction mixture is heated to 60°. Then 21 g of chloroacetone are added dropwise within a short period of time and the reaction mixture is stirred at 70° for 20 hours and then, at 20°, is filtered over Celite. The filtrate is concentrated by evaporation. The residue is stirred with diisopropyl ether and filtered with suction. 45 g of crystals of the title compound having a melting point of 66-67° are thus obtained. | COc1nn(CC(C)=O)c(=O)s1 | null | null | null |
407,819 | ord_dataset-d5bb2294ac964841b8ffc9e0a34e93af | null | 1998-01-01T00:07:00 | true | Cl.C[O:3][C:4](=[O:29])[C@H:5]([CH2:19][C:20]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[NH:22][CH:21]=1)[NH:6][C:7](=[O:18])[C@@H:8]([CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[NH:9][CH3:10].[C:30]1([CH3:39])[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([OH:38])=O)[CH:31]=1>>[CH3:39][C:30]1[CH:31]=[C:32]([CH:33]=[CH:34][CH:35]=1)[C:36]([N:9]([CH3:10])[C@@H:8]([C:7]([NH:6][C@H:5]([C:4]([OH:29])=[O:3])[CH2:19][C:20]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[NH:22][CH:21]=1)=[O:18])[CH2:11][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)=[O:38] | CN[C@H](Cc1ccccc1)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)OC | Cc1cccc(C(=O)O)c1 | null | Cl | 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 | Coupling of N-methyl-(D)-phenylalanyl-(L)-tryptophan methyl ester hydrochloride (see example 1) with m-toluic acid according to example 12 followed by hydrolysis of the methyl ester moiety according to example 1 gives N-(3-methylbenzoyl)-N-methyl-(D)-phenylalanyl-(L)-tryptophan; FAB-MS m/e 484 (M+H)+. | Cc1cccc(C(=O)N(C)[C@H](Cc2ccccc2)C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)O)c1 | null | null | null |
1,638,137 | ord_dataset-f0794d5ded7a4d3fab45cc3d7a89ee3d | null | 2015-01-01T00:09:00 | true | [CH3:1][N:2]1[CH:6]=[C:5]([CH:7]=[O:8])[C:4]([CH:9]([F:11])[F:10])=[N:3]1.S(Cl)([Cl:15])(=O)=O>ClC1C=CC=CC=1>[CH3:1][N:2]1[CH:6]=[C:5]([C:7]([Cl:15])=[O:8])[C:4]([CH:9]([F:10])[F:11])=[N:3]1 | O=S(=O)(Cl)Cl | Cn1cc(C=O)c(C(F)F)n1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Clc1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | null | The solution of 16 g (100 mol) of 1-methyl-3-difluoromethyl-1H-pyrazole-4-carbaldehyde, 13.5 g (100 mmol) of sulphuryl chloride and 0.2 g of 2,2-azoisobutyronitrile in 50 ml of chlorobenzene was stirred at 70-80° C. for 6 h. The reaction solution was concentrated. 18.8 g of the product (95% yield) was obtained as an oil with a purity (GC) of 98%. | Cn1cc(C(=O)Cl)c(C(F)F)n1 | null | 96.6 | null |
1,243,131 | ord_dataset-c544c0c663f54dbea4ddb52ddde7934e | null | 2013-01-01T00:01:00 | true | Br[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[O:11][CH3:12].[F:13][C:14]([F:19])([F:18])C([O-])=O.[K+].C1(C)C=CC=CC=1>CN(C)C=O>[CH3:12][O:11][C:3]1[CH:4]=[C:5]([N+:8]([O-:10])=[O:9])[CH:6]=[CH:7][C:2]=1[C:14]([F:19])([F:18])[F:13] | COc1cc([N+](=O)[O-])ccc1Br | O=C([O-])C(F)(F)F | null | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | Cc1ccccc1 | null | null | null | null | null | null | null | null | null | 155 | 20 | To a solution of 1-bromo-2-methoxy-4-nitrobenzene (10.0 g, 43.0 mmol) in N,N-dimethylformamide (200 mL) were added potassium trifluoroacetate (13.0 g, 86.0 mmol), copper iodide(I) and toluene (40 mL), and the mixture was stirred at 155° C. for 20 hr while removing the produced water drops by a Dean-Stark trap. The reaction mixture was cooled to room temperature, and concentrated under reduced pressure. The residue was suspended in ethyl acetate (300 mL), the insoluble material was filtered off, and the filtrate was washed with water (150 mL) and saturated brine (150 mL), and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=98/2→88/12). The obtained solution was concentrated under reduced pressure to give the title compound (6.86 g, 72%) as a pale-yellow oil. | COc1cc([N+](=O)[O-])ccc1C(F)(F)F | null | 72.1 | null |
32,397 | ord_dataset-8f61d01cf5b34e85a3ccc89f8901797b | null | 1977-01-01T00:11:00 | true | [C:1]([C:4]1[CH:12]=[CH:11][CH:10]=[CH:9][C:5]=1[C:6]([OH:8])=O)(=O)[CH3:2].[CH2:13]([NH2:17])[CH2:14][CH2:15][NH2:16]>>[CH3:2][C:1]12[NH:17][CH2:13][CH2:14][CH2:15][N:16]1[C:6](=[O:8])[C:5]1[C:4]2=[CH:12][CH:11]=[CH:10][CH:9]=1 | CC(=O)c1ccccc1C(=O)O | NCCCN | 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 | 16.4 Parts of o-acetyl-benzoic acid and 8 parts of 1,3-propanediamine are heated for 2 hours at 150°-160°. The reaction mixture is then distilled under high vacuum. The 10b-methyl-1,3,4,10b-tetrahydro-pyrimido[2,1-a]isoindol -6(2H)-one obtained of the formula ##STR35## boils at 120°-123°/0.1 Torr. After recrystallising from ethyl acetate/benzine, it melts at 64.5°. The following compounds are obtained in an analogous manner: | CC12NCCCN1C(=O)c1ccccc12 | null | null | null |
251,240 | ord_dataset-41ea179beba54bed8cd874a5ec3469f7 | null | 1992-01-01T00:07:00 | true | O.[C:2]1([CH3:11])[CH:7]=[CH:6][C:5]([S:8]([O-:10])=[O:9])=[CH:4][CH:3]=1.[Na+].Br[CH2:14][CH2:15][CH:16]1[O:20][CH2:19][CH2:18][O:17]1.N>CN(C=O)C>[CH2:19]1[O:20][CH:16]([CH2:15][CH2:14][S:8]([C:5]2[CH:6]=[CH:7][C:2]([CH3:11])=[CH:3][CH:4]=2)(=[O:10])=[O:9])[O:17][CH2:18]1 | BrCCC1OCCO1 | Cc1ccc(S(=O)[O-])cc1 | null | N | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CN(C)C=O | null | null | null | null | null | null | null | null | null | 0 | null | A mixture of sodium 4-toluenesulphinate monohydrate (37.2 g, 0.19 mole) and 2-(2-bromoethyl)-1,3-dioxolane (20 ml, 0.17 mole) in dry DMF (100 ml) was stirred at room temperature for 64h, resulting in a homogenous solution. This was poured into ice/water (1 liter) containing conc. ammonia solution (100 ml) and stirred vigorously until a white precipitate formed. The solid was filtered off, washed with water, dried and recrystallised from propan-2-ol/ether to give the title compound (D24) as a white solid (28.7 g, 66%) m.p. 78°-80° C. | Cc1ccc(S(=O)(=O)CCC2OCCO2)cc1 | null | 65.9 | null |
436,669 | ord_dataset-a1e9aa99368e4e5da8b1786b1c05521d | null | 1999-01-01T00:08:00 | true | [CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][C:10]([F:34])=[C:11]([C:15]4[CH:16]=[C:17]5[C:21](=[CH:22][CH:23]=4)[CH2:20][N:19](S(C4C=CC(C)=CC=4)(=O)=O)[CH2:18]5)[C:12]=3[CH3:14])[C:7](=[O:35])[C:6]([C:36]([OH:38])=[O:37])=[CH:5]2)[CH2:3][CH2:2]1.C1(O)C=CC=CC=1.C(O)(=O)CC.[BrH:51]>>[BrH:51].[CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][C:10]([F:34])=[C:11]([C:15]4[CH:16]=[C:17]5[C:21](=[CH:22][CH:23]=4)[CH2:20][NH:19][CH2:18]5)[C:12]=3[CH3:14])[C:7](=[O:35])[C:6]([C:36]([OH:38])=[O:37])=[CH:5]2)[CH2:2][CH2:3]1 | Cc1ccc(S(=O)(=O)N2Cc3ccc(-c4c(F)cc5c(=O)c(C(=O)O)cn(C6CC6)c5c4C)cc3C2)cc1 | null | null | Br | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCC(=O)O | Oc1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | In 5.3 ml of 47% hydrobromic acid was suspended 0.53 g of 1-cyclopropyl-6-fluoro-8-methyl-7-[2-(p-toluenesulfonyl)isoindolin-5-yl]-1,4-dihydro-4-oxoquinoline-3 carboxylic acid, and 0.28 g of phenol and 3.2 ml of propionic acid were added to the suspension, after which the resulting mixture was heated under reflux for one hour under a nitrogen stream. The reaction mixture was concentrated under reduced pressure, and ethanol was added to the residue obtained, after which the crystals formed were collected by filtration, to obtain 0.38 g of colorless, crystalline 1-cyclopropyl-6-fluoro-8-methyl-7-(isoindolin-5-yl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid hydrobromide. The hydrobromide obtained was suspended in 3.8 ml of ethanol and then dissolved in 7.6 ml of 0.5N aqueous sodium hydroxide solution, after which a carbon dioxide gas was blown into the solution. The crystals formed were collected by filtration, to obtain 0.27 g of colorless, crystalline 1-cyclopropyl-6-fluoro-8-methyl-7-(isoindolin-5-yl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid. | Cc1c(-c2ccc3c(c2)CNC3)c(F)cc2c(=O)c(C(=O)O)cn(C3CC3)c12 | null | null | null |
959,083 | ord_dataset-ed65749688da45af8a8432967b017729 | null | 2010-01-01T00:05:00 | true | [CH:1]1([C:6]2[CH:7]=[C:8]3[C:13](=[CH:14][CH:15]=2)[C:12](=[O:16])[NH:11][C:10](=[O:17])[CH2:9]3)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:18][O:19][CH:20](OC)OC>C(O)(=O)C>[CH:1]1([C:6]2[CH:7]=[C:8]3[C:13](=[CH:14][CH:15]=2)[C:12](=[O:16])[NH:11][C:10](=[O:17])[C:9]3=[CH:18][O:19][CH3:20])[CH2:2][CH2:3][CH2:4][CH2:5]1 | O=C1Cc2cc(C3CCCC3)ccc2C(=O)N1 | COC(OC)OC | null | null | null | null | 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 | 90 | null | A mixture of 6-cyclopentyl-4H-isoquinoline-1,3-dione (222 mg, 0.97 mmole), 10 mL of acetic acid and trimethylorthoformate (212 mg, 2.0 mmole) is stirred and heated to 90° C. After 2 hours at that temperature the reaction mixture is cooled and the solvents were removed in-vacuo and the residue taken up in 4% methanol in dichloromethane, passed through a short pad of Florisil and eluted with 4% methanol in dichloromethane. The eluate is evaporated and the product is treated with 4:1 hexanes-ethyl acetate and collected by filtration to give a yellow solid, 165 mg, (62%), MS (ES+): m/z 272.2 (M+H). | COC=C1C(=O)NC(=O)c2ccc(C3CCCC3)cc21 | null | null | null |
1,600,877 | ord_dataset-e8c6a25568b64529b960953990e6921f | null | 2015-01-01T00:06:00 | true | [F:1][C:2]([F:14])([F:13])[C:3]1[CH:12]=[CH:11][C:10]2[CH:8]3[O:9][CH:7]3[CH2:6][C:5]=2[CH:4]=1.[CH3:15][C@@H:16]1[NH:21][CH2:20][CH2:19][N:18]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:17]1>C(O)C>[OH:9][CH:7]1[CH2:6][C:5]2[C:10](=[CH:11][CH:12]=[C:3]([C:2]([F:14])([F:13])[F:1])[CH:4]=2)[CH:8]1[N:21]1[CH2:20][CH2:19][N:18]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:17][C@@H:16]1[CH3:15] | C[C@H]1CN(C(=O)OC(C)(C)C)CCN1 | FC(F)(F)c1ccc2c(c1)CC1OC21 | 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 | 95 | null | A mixture of 4-(trifluoromethyl)-6,6a-dihydro-1aH-indeno[1,2-b]oxirene (1.2 g, 6.0 mmol) and tert-butyl (3S)-3-methylpiperazine-1-carboxylate (1.4 g, 7.2 mol) in ethanol (20 mL) was refluxed overnight. Another gram of tert-butyl (3S)-3-methylpiperazine-1-carboxylate was added. The mixture was transferred into a sealed flask and heated to 95° C. for 2 days. The solvent was concentrated and the residue was purified by flash chromatography eluting with 25% EtOAc/hexane, followed by 5% MeOH/EtOAc+0.5% concentrated NH4OH. Two isomers were isolated. Isomer 1 (fast moving isomer): 0.45 g; MS calculated for the C20H27F3N2O3 (M+H)+401; found 401.1. Isomer 2 (slow moving isomer): 0.38 g; MS found 401.1. | C[C@H]1CN(C(=O)OC(C)(C)C)CCN1C1c2ccc(C(F)(F)F)cc2CC1O | null | null | null |
1,334,917 | ord_dataset-08852243bba44cb28769a5833f1515fe | null | 2013-01-01T00:09:00 | true | CC1C=CC(S(O[CH2:12][C@H:13]2[O:18][C:17]3[CH:19]=[C:20]([S:23]([CH3:26])(=[O:25])=[O:24])[CH:21]=[CH:22][C:16]=3[O:15][CH2:14]2)(=O)=O)=CC=1.[CH3:27][CH:28]([CH3:31])[CH2:29][NH2:30]>C(#N)C>[CH3:27][CH:28]([CH3:31])[CH2:29][NH:30][CH2:12][C@H:13]1[O:18][C:17]2[CH:19]=[C:20]([S:23]([CH3:26])(=[O:24])=[O:25])[CH:21]=[CH:22][C:16]=2[O:15][CH2:14]1 | Cc1ccc(S(=O)(=O)OC[C@@H]2COc3ccc(S(C)(=O)=O)cc3O2)cc1 | CC(C)CN | 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 | 120 | null | A mixture of [(2S)-7-(methylsulfonyl)-2,3-dihydro-1,4-benzodioxin-2-yl]methyl 4-methylbenzenesulfonate (0.2 g, 0.5 mmol), 2-methylpropane-1-amine (1 ml) and ACN (2 ml) was heated under microwave radiation at 120° C. for 30 min. Purification on SCX-3 column (TEA/MeOH) and flash column chromatography (EtOAc/MeOH). Yield: 0.1 g, 77%. The amine was converted to the hydrochloric acid salt and crystallized from MeOH/Et2O. M.p. 213° C. MS m/z (rel. intensity, 70 eV) 299 (M+, 4), 256 (16), 207 (11), 86 (bp), 57 (8). [α]=+65° (MeOH). | CC(C)CNC[C@@H]1COc2ccc(S(C)(=O)=O)cc2O1 | null | null | null |
159,306 | ord_dataset-41c90677d90b4fa5836ab66e2f5b4f51 | null | 1987-01-01T00:06:00 | true | [CH2:1]([O:3][C:4](=[O:12])[C:5]1[C:6](=[CH:8][CH:9]=[CH:10][CH:11]=1)[NH2:7])[CH3:2].[C:13](O)(=O)[C:14]1C(=CC=C[CH:20]=1)N>>[CH2:1]([O:3][C:4](=[O:12])[C:5]1[C:6](=[CH:8][CH:9]=[CH:10][CH:11]=1)[NH:7][CH:14]([CH3:20])[CH3:13])[CH3:2] | CCOC(=O)c1ccccc1N | Nc1ccccc1C(=O)O | 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 | Following the reaction procedure of Example 8 but substituted a molar equivalent amount of anthranilic acid ethyl ester for the anthranilic acid, there is obtained N-isopropylanthranilic acid ethyl ester. | CCOC(=O)c1ccccc1NC(C)C | null | null | null |
58,294 | ord_dataset-cb9f452f8418479ab5fd99c835dbe015 | null | 1979-01-01T00:09:00 | true | [CH:1]([NH:4][C:5]1[C:18]2[C:17](=[O:19])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][C:15]=3[OH:20])[C:10](=[O:21])[C:9]=2[C:8](Br)=[CH:7][CH:6]=1)([CH3:3])[CH3:2].[CH:23]1([NH2:29])[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1.C([O-])(=O)C.[K+].[Cl-]>CO>[CH:1]([NH:4][C:5]1[C:18]2[C:17](=[O:19])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][C:15]=3[OH:20])[C:10](=[O:21])[C:9]=2[C:8]([NH:29][CH:23]2[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)=[CH:7][CH:6]=1)([CH3:3])[CH3:2] | CC(C)Nc1ccc(Br)c2c1C(=O)c1c(O)cccc1C2=O | NC1CCCCC1 | null | CC(=O)[O-] | [Cl-] | [K+] | 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 | 18 g of 1-isopropylamino-4-bromo-8-hydroxy-anthraquinone, 36 ml of cyclohexylamine, 6.5 of potassium acetate and catalytic amounts of copperI chloride are stirred at 80°-90° until only a little starting material is still detectable. The mixture is now diluted with 36 ml of methanol and the reaction product which has separated out is filtered off at 60°, washed with boiling hot methanol, finally stirring with dilute hydrochloric acid, filtered off, washed until neutral and dried. | CC(C)Nc1ccc(NC2CCCCC2)c2c1C(=O)c1c(O)cccc1C2=O | null | null | null |
395,866 | ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a | null | 1998-01-01T00:03:00 | true | [NH2:1][C:2]1[CH:3]=[C:4]([C:8](=[O:10])[CH3:9])[CH:5]=[CH:6][CH:7]=1.[NH2:11][C:12]1[N:17]=[C:16](Cl)[CH:15]=[C:14]([CH3:19])[N:13]=1.Cl.[OH-].[K+]>O>[C:8]([C:4]1[CH:3]=[C:2]([NH:1][C:16]2[CH:15]=[C:14]([CH3:19])[N:13]=[C:12]([NH2:11])[N:17]=2)[CH:7]=[CH:6][CH:5]=1)(=[O:10])[CH3:9] | CC(=O)c1cccc(N)c1 | Cc1cc(Cl)nc(N)n1 | null | Cl | [K+] | [OH-] | 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 | Compound No. 15: A suspension of m-aminoacetophenone (2.7 g) and 2-amino-4-chloro-6-methylpyrimidine (2.87 g) in 40 mL water was treated with 1.7 mL concentrated HCl and heated at reflux for 1 hour. Addition of 40 mL 1N KOH gave a light buff solid, which was filtered out and dried to give 3.8 g 4-(3-acetylphenyl)amino-2-amino-6-methylpyrimidine, mp 196°-98° C. | CC(=O)c1cccc(Nc2cc(C)nc(N)n2)c1 | null | 78.5 | null |
947,790 | ord_dataset-3feb2a95f66e4706a4a50c977ccd9bf8 | null | 2010-01-01T00:04:00 | true | ClC(Cl)(Cl)[C:3]([C:5]1[N:14]2[C:8]([CH2:9][N:10]([C:19](=[O:29])[CH2:20][S:21][C:22]3[CH:27]=[CH:26][C:25]([Br:28])=[CH:24][CH:23]=3)[C:11]3[CH:18]=[CH:17][CH:16]=[CH:15][C:12]=3[CH2:13]2)=[CH:7][CH:6]=1)=[O:4].[F:32][C:33]([F:43])([F:42])[C:34]1[CH:35]=[C:36]([CH:39]=[CH:40][CH:41]=1)[CH2:37][NH2:38]>>[Br:28][C:25]1[CH:24]=[CH:23][C:22]([S:21][CH2:20][C:19]([N:10]2[C:11]3[CH:18]=[CH:17][CH:16]=[CH:15][C:12]=3[CH2:13][N:14]3[C:5]([C:3]([NH:38][CH2:37][C:36]4[CH:39]=[CH:40][CH:41]=[C:34]([C:33]([F:32])([F:42])[F:43])[CH:35]=4)=[O:4])=[CH:6][CH:7]=[C:8]3[CH2:9]2)=[O:29])=[CH:27][CH:26]=1 | O=C(CSc1ccc(Br)cc1)N1Cc2ccc(C(=O)C(Cl)(Cl)Cl)n2Cc2ccccc21 | NCc1cccc(C(F)(F)F)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 synthesized in the manner of Example 81 from 2,2,2-trichloro-1-[10-{[(4-bromophenyl)thio]acetyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-yl]-ethanone of Example 80 and 3-trifluoromethylbenzylamine, m.p. 102° C. MS [(+)ESI, m/z]: 614 [M+H]+ Anal. Calcd for C29H23BrF3N3O2S: C, 56.69; H, 3.77; N, 6.84. Found: C, 56.79; H, 3.66; N, 6.76. | O=C(NCc1cccc(C(F)(F)F)c1)c1ccc2n1Cc1ccccc1N(C(=O)CSc1ccc(Br)cc1)C2 | null | null | null |
1,362,972 | ord_dataset-d932d1d683704a8bad3d064bcb197acc | null | 2013-01-01T00:11:00 | true | [C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([N:14]3[CH:18]=[C:17]([CH3:19])[N:16]=[CH:15]3)=[CH:11][CH:12]=2)[CH:7]([NH:20][C:21]2[N:26]=[CH:25][C:24]([C:27]([OH:29])=[O:28])=[CH:23][CH:22]=2)[CH2:6][CH:5]1[CH3:30])(=[O:3])[CH3:2].Cl.[CH3:32]O>>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([N:14]3[CH:18]=[C:17]([CH3:19])[N:16]=[CH:15]3)=[CH:11][CH:12]=2)[C@H:7]([NH:20][C:21]2[N:26]=[CH:25][C:24]([C:27]([O:29][CH3:32])=[O:28])=[CH:23][CH:22]=2)[CH2:6][C@@H:5]1[CH3:30])(=[O:3])[CH3:2] | CC(=O)N1c2ccc(-n3cnc(C)c3)cc2C(Nc2ccc(C(=O)O)cn2)CC1C | CO | null | Cl | 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 | 25 | 1 | A solution of 6-{[1-acetyl-2-methyl-6-(4-methyl-1H-imidazol-1-yl)-1,2,3,4-tetrahydro-4-quinolinyl]amino}-3-pyridinecarboxylic acid (for a preparation see example 143) (40 mg, 0.099 mmol) in dry methanol (2 mL) was treated at room temperature with HCl (4M in 1,4-dioxane, 200 μl, 0.800 mmol) and the resulting mixture was stirred at this temperature for one hour. Another portion of HCl (4M in 1,4-dioxane, 200 μl, 0.800 mmol) was added and the mixture was refluxed for 1 hour then cooled to room temperature and concentrated in vacuo. The residue was purified using MDAP (modifier: ammonium formate) to give methyl 6-{[(cis)-1-acetyl-2-methyl-6-(4-methyl-1H-imidazol-1-yl)-1,2,3,4-tetrahydro-4-quinolinyl]amino}-3-pyridinecarboxylate (12 mg, 0.029 mmol, 29%) as a white solid. | COC(=O)c1ccc(N[C@@H]2C[C@H](C)N(C(C)=O)c3ccc(-n4cnc(C)c4)cc32)nc1 | null | 29 | null |
1,596,780 | ord_dataset-e8c6a25568b64529b960953990e6921f | null | 2015-01-01T00:06:00 | true | [N:1]1[N:2]([C:10]2[N:31]=[CH:30][CH:29]=[CH:28][C:11]=2[C:12]([NH:14][CH:15]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:16]([OH:20])[C:17](O)=[O:18])=[O:13])[CH:3]=[C:4]2[C:9]=1[CH2:8][CH2:7][CH2:6][CH2:5]2.Cl.[CH3:33][O:34][NH2:35]>>[OH:20][CH:16]([C:17]([NH:35][O:34][CH3:33])=[O:18])[CH:15]([NH:14][C:12](=[O:13])[C:11]1[CH:28]=[CH:29][CH:30]=[N:31][C:10]=1[N:2]1[CH:3]=[C:4]2[C:9]([CH2:8][CH2:7][CH2:6][CH2:5]2)=[N:1]1)[CH2:21][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1 | CON | O=C(NC(Cc1ccccc1)C(O)C(=O)O)c1cccnc1-n1cc2c(n1)CCCC2 | null | Cl | 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 was carried out in analogy to reaction step 3.1 by reacting 3-[2-(4,5,6,7-tetrahydro-2H-indazol-2-yl)nicotinamido]-2-hydroxy-4-phenylbutanoic acid and O-methylhydroxylamine hydrochloride. | CONC(=O)C(O)C(Cc1ccccc1)NC(=O)c1cccnc1-n1cc2c(n1)CCCC2 | null | null | null |
78,883 | ord_dataset-0c37e633e9814a6e886187796cacf216 | null | 1981-01-01T00:03:00 | true | [C:1]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[Na].[CH3:13][C:14]([CH3:18])=[C:15]=[CH:16]Br.O>C(O)C>[CH3:13][C:14]([CH3:18])([C:15]#[CH:16])[CH:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])[C:1]([O:9][CH2:10][CH3:11])=[O:8] | CCOC(=O)CC(=O)OCC | CC(C)=C=CBr | null | [Na] | 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 | Diethyl malonate (34.8 g.) was added to a solution of sodium (5.0 g.) in ethanol (500 ml.) and the mixture stirred for a few minutes. 3,3-Dimethyl-1-bromoallene (32.0 g.) was then added dropwise at the ambient temperature after which the mixture was refluxed for 3 hours. The ethanolic solution obtained was poured into an excess of water and the mixture extracted with chloroform (3×200 ml.). The extracts were combined, dried with anhydrous sodium sulphate and evaporated and the residual oil distilled under reduced pressure to yield ethyl 3,3-dimethyl-2-ethoxycarbonylpent-4-ynoate, as an oil b.p. 56°-60°/0.1 mm. Hg. | C#CC(C)(C)C(C(=O)OCC)C(=O)OCC | null | null | null |
975,642 | ord_dataset-f886e51ba1484c76a94bce1482f1eab9 | null | 2010-01-01T00:07:00 | true | [Br:1]N1C(=O)CCC1=O.OS(O)(=O)=O.[O:14]1[C:18]2[CH:19]=[CH:20][C:21]([C:23]3[C:24]4[CH2:38][O:37][C:36](=[O:39])[C:25]=4[CH:26]=[C:27]4[C:35]=3[C:31]3[O:32][CH2:33][O:34][C:30]=3[CH:29]=[CH:28]4)=[CH:22][C:17]=2[O:16][CH2:15]1>C1COCC1.CCOC(C)=O>[O:14]1[C:18]2[CH:19]=[CH:20][C:21]([C:23]3[C:24]4[CH2:38][O:37][C:36](=[O:39])[C:25]=4[CH:26]=[C:27]4[C:35]=3[C:31]3[O:32][CH2:33][O:34][C:30]=3[CH:29]=[C:28]4[Br:1])=[CH:22][C:17]=2[O:16][CH2:15]1 | O=C1OCc2c1cc1ccc3c(c1c2-c1ccc2c(c1)OCO2)OCO3 | O=C1CCC(=O)N1Br | null | O=S(=O)(O)O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOC(C)=O | C1CCOC1 | null | null | null | null | null | null | null | null | null | 25 | 20 | N-bromosuccinimide (10.7 mg, 0.06 mmol) and concentrated H2SO4 (5 μL) were added to a solution of 2 (15.4 mg, 0.044 mmol) in THF (1 mL). The solution was stirred at room temperature for 20 h, and then diluted with EtOAc (30 μL). The same workup and purification procedure as described for the isolation of 37 gave 38 (12 mg, 64%) as a pale yellow powder. mp 256° C. (decomp.); 1H NMR (CDCl3) δ 8.89 (s, 1H, H4), 7.65 (s, 1H, H6), 6.76-6.91 (m, 3H, H2′+H5′+H6′), 6.08 (AB, 2H, 3′,4′-OCH2O—, Δδ=8.7 Hz, J=1.5 Hz), 5.97 (AB, 2H, 7,8-OCH2O—, Δδ=7.8 Hz, J=1.5 Hz), 5.22 (q, 2H, lactone-CH2—, J=8.4 Hz); MS (EI) m/z 428 [M+2]+, 426 [M]+. | O=C1OCc2c1cc1c(Br)cc3c(c1c2-c1ccc2c(c1)OCO2)OCO3 | null | 63.8 | null |
102,083 | ord_dataset-72d9f7ef86df410fac4765c9632d459b | null | 1983-01-01T00:01:00 | true | O=[C:2]1[CH2:7][CH2:6][C:5]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=2)([C:8]#[N:9])[CH2:4][CH2:3]1.[C:16]1([C:22]2([C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.CC1C=CC(S(O)(=O)=O)=CC=1.CC1C=CC=CC=1>O>[C:8]([C:5]1([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=2)[CH2:6][CH2:7][C:2]([N:25]2[CH2:24][CH2:23][C:22]([C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)([C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH2:27][CH2:26]2)=[CH:3][CH2:4]1)#[N:9] | CCOC(=O)C1(c2ccccc2)CCNCC1 | N#CC1(c2ccccn2)CCC(=O)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 | O | null | null | null | null | null | null | null | null | null | null | null | A mixture of 4.5 parts of 4-oxo-1-(2-pyridinyl)cyclohexanecarbonitrile, 5.2 parts of ethyl 4-phenyl-4-piperidinecarboxylate, 1 part of 4-methylbenzenesulfonic acid and 225 parts of methylbenzene is stirred and refluxed overnight using a water-separator. The reaction mixture is evaporated and the residue is crystallized from 2-propanol, yielding 4.5 parts (45%) of ethyl 1-[4-cyano-4-(2-pyridinyl)-1-cyclohexeneyl]-4-phenyl-4-piperidinecarboxylate; mp. 160° C. | CCOC(=O)C1(c2ccccc2)CCN(C2=CCC(C#N)(c3ccccn3)CC2)CC1 | null | 45 | null |
59,779 | ord_dataset-09e9a37ee5794dc28c0ad7bf7a442c18 | null | 1979-01-01T00:11:00 | true | [C:1]1([SH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH:8]([C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14])[CH2:9][C:10]([OH:12])=[O:11]>ClCCl>[C:1]1([S:7][O:12][C:10](=[O:11])[CH2:9][NH:8][C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:14])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1 | Sc1ccccc1 | O=C(O)CNC(=O)OCc1ccccc1 | 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 | null | null | Using thiophenol and Z-Gly.OH, Example 78 was repeated; except that dichloromethane was used in place of ethyl acetate as the extraction solvent, to obtain N-benzyloxycarbonyl-glycine-phenythio ester (hereinafter represented by ##STR12## in a yield of 62%. | O=C(CNC(=O)OCc1ccccc1)OSc1ccccc1 | null | 62 | null |
965,666 | ord_dataset-03ba810b7f464a06b5d8787af2e8b64e | null | 2010-01-01T00:06:00 | true | [N:1]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[C:7](O)=O.Cl.CN(C)CCCN=C=NCC.N1C=CC=CC=1.[N:28]1[CH:33]=[CH:32][CH:31]=[C:30]([O:34][C:35]2[CH:36]=[C:37]([NH2:49])[C:38]([NH2:48])=[CH:39][C:40]=2[O:41][C:42]2[CH:43]=[N:44][CH:45]=[CH:46][CH:47]=2)[CH:29]=1>C(OCC)(=O)C>[N:1]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[C:7]1[NH:49][C:37]2[CH:36]=[C:35]([O:34][C:30]3[CH:29]=[N:28][CH:33]=[CH:32][CH:31]=3)[C:40]([O:41][C:42]3[CH:43]=[N:44][CH:45]=[CH:46][CH:47]=3)=[CH:39][C:38]=2[N:48]=1 | Nc1cc(Oc2cccnc2)c(Oc2cccnc2)cc1N | O=C(O)c1cnccn1 | null | CCN=C=NCCCN(C)C | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOC(C)=O | c1ccncc1 | null | null | null | null | null | null | null | null | null | 25 | 8 | 7.7 mg of pyrazine-2-carboxylic acid and 20 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide monohydrochloride were added to a pyridine (1 ml) solution of 15 mg of 4,5-bis(pyridin-3-yloxy)-benzene-1,2-diamine obtained in Example 1 (step 3), and the reaction liquid was stirred overnight at room temperature. The reaction liquid was diluted with ethyl acetate, washed with saturated sodium bicarbonate solution, water and saturated saline in order, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and the resulting residue was suspended in 1 ml of phosphorus oxychloride, and the reaction liquid was stirred overnight at 100° C. Phosphorus oxychloride was evaporated away under reduced pressure, and this was diluted with ethyl acetate, washed with saturated sodium bicarbonate solution and saturated saline in order, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and the residue was purified through partitioning thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=15/1+0.1% aqueous ammonia) to obtain the entitled compound as a yellow solid. | c1cncc(Oc2cc3nc(-c4cnccn4)[nH]c3cc2Oc2cccnc2)c1 | null | null | null |
1,065,588 | ord_dataset-ffbef48837674f39816de887b5dc8bae | null | 2011-01-01T00:06:00 | true | [F:1][C:2]([F:18])([F:17])[CH:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1[C:15]([CH3:16])=[CH:14][S:13][CH:12]=1)[OH:4].[NH2:19][C:20]1[N:25]=[C:24](Cl)[CH:23]=[C:22]([Cl:27])[N:21]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O1CCOCC1>C(OCC)(=O)C>[Cl:27][C:22]1[CH:23]=[C:24]([O:4][CH:3]([C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=2[C:11]2[C:15]([CH3:16])=[CH:14][S:13][CH:12]=2)[C:2]([F:1])([F:17])[F:18])[N:25]=[C:20]([NH2:19])[N:21]=1 | Cc1cscc1-c1ccccc1C(O)C(F)(F)F | Nc1nc(Cl)cc(Cl)n1 | null | O=C([O-])[O-] | [Cs+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1COCCO1 | CCOC(C)=O | null | null | null | null | null | null | null | null | null | 110 | null | A mixture of 2,2,2-trifluoro-1-[2-(4-methyl-thiophen-3-yl)-phenyl]-ethanol (100 mg, 0.37 mmol), 2-amino-4,6-dichloro-pyrimidine (54 mg, 0.33 mmol), cesium carbonate (481 mg, 1.48 mmol) and 1,4-dioxane (1 ml) was heated at 110° C. overnight. The reaction mixture was cooled to room temperature; 10 ml of ethyl acetate was added. The mixture was then filtered through Celite, the filtrate was concentrated to give 100 mg of 4-chloro-6-{2,2,2-trifluoro-1-[2-(4-methyl-thiophen-3-yl)-phenyl]-ethoxy}-pyrimidin-2-ylamine, yield: 76%. | Cc1cscc1-c1ccccc1C(Oc1cc(Cl)nc(N)n1)C(F)(F)F | null | 75.8 | null |
463,925 | ord_dataset-6c36eb0f817d4144988b8963c5d58879 | null | 2000-01-01T00:05:00 | true | [N+:1]([C:4]1[CH:5]=[C:6]([OH:13])[CH:7]=[C:8]([N+:10]([O-:12])=[O:11])[CH:9]=1)([O-:3])=[O:2].Br[CH2:15][C:16]#[N:17].C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>CC(=O)CC>[N+:1]([C:4]1[CH:5]=[C:6]([CH:7]=[C:8]([N+:10]([O-:12])=[O:11])[CH:9]=1)[O:13][CH2:15][C:16]#[N:17])([O-:3])=[O:2] | N#CCBr | O=[N+]([O-])c1cc(O)cc([N+](=O)[O-])c1 | null | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCC(C)=O | CCOC(C)=O | null | null | null | null | null | null | null | null | null | 70 | null | 3,5-Dinitrophenol (15.0 g) and 10.75 g of bromoacetonitrile were dissolved in 85 ml of 2-butanone and the solution was treated with 33.78 g of potassium carbonate. The heterogenous mixture was stirred and heated at 70° C. for 5 hours, cooled to room temperature, poured into ethyl acetate, washed with water, dried over magnesium sulfate, and evaporated. The residue was purified by silica gel chromatography eluting with dichloromethane/hexane (3:1) to give 11.24 g of (3,5-dinitrophenoxy)-acetonitrile as a light yellow solid. | N#CCOc1cc([N+](=O)[O-])cc([N+](=O)[O-])c1 | null | 61.8 | null |
1,133,787 | ord_dataset-aaeaab5f3720492494c1cbbdd0ed2820 | null | 2012-01-01T00:02:00 | true | C[O:2][C:3](=[O:52])[C:4]1[CH:51]=[CH:50][C:7]([C:8]([NH:10][C:11]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([S:20]([C:23]4[CH:28]=[C:27]([F:29])[CH:26]=[C:25]([F:30])[CH:24]=4)(=[O:22])=[O:21])[CH:18]=3)[N:13]([C:31]([C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[N:12]=2)=[O:9])=[CH:6][CH:5]=1.O1CCCC1.O.[OH-].[Li+]>O>[F:30][C:25]1[CH:24]=[C:23]([S:20]([C:17]2[CH:18]=[C:19]3[C:14](=[CH:15][CH:16]=2)[N:13]([C:31]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[N:12]=[C:11]3[NH:10][C:8](=[O:9])[C:7]2[CH:50]=[CH:51][C:4]([C:3]([OH:52])=[O:2])=[CH:5][CH:6]=2)(=[O:22])=[O:21])[CH:28]=[C:27]([F:29])[CH:26]=1 | COC(=O)c1ccc(C(=O)Nc2nn(C(c3ccccc3)(c3ccccc3)c3ccccc3)c3ccc(S(=O)(=O)c4cc(F)cc(F)c4)cc23)cc1 | null | null | [Li+] | [OH-] | 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 | 25 | 8 | A mixture of N-[5-(3,5-difluoro-benzenesulfonyl)-1-trityl-1H-indazol-3-yl]-terephthalamic acid methyl ester (400 mg, 0.56 mmol), tetrahydrofuran (8 mL), water (4 mL) and lithium hydroxide hydrate (35 mg, 1.5 eq) was stirred at room temperature overnight. The solvents were evaporated to dryness. The residue was taken up with ethyl acetate, washed with 5% aqueous solution of potassium bisulfate, brine, dried over sodium sulfate and evaporated to dryness affording the crude title compound that was used as such for the next step without further purification. | O=C(O)c1ccc(C(=O)Nc2nn(C(c3ccccc3)(c3ccccc3)c3ccccc3)c3ccc(S(=O)(=O)c4cc(F)cc(F)c4)cc23)cc1 | null | null | null |
931,676 | ord_dataset-d8a5dc784dde4465894ec7c69d2e3ba6 | null | 2010-01-01T00:01:00 | true | [Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6]Br)=[CH:4][CH:3]=1.[CH3:10][CH:11]1[CH2:16][NH:15][CH2:14][CH2:13][NH:12]1.C(N(CC)CC)C.C(=O)(O)[O-].[Na+]>CN(C=O)C>[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][N:15]2[CH2:14][CH2:13][NH:12][CH:11]([CH3:10])[CH2:16]2)=[CH:4][CH:3]=1 | Clc1ccc(CBr)cc1 | CC1CNCCN1 | null | O=C([O-])O | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(CC)CC | CN(C)C=O | null | null | null | null | null | null | null | null | null | 25 | 16 | 3.49 g (17.0 mmol) 4-Chlorobenzylbromide was added dropwise to a mixture of 2.04 g (20.4 mmol) 2-Methyl piperazine and 2.40 ml (17 mmol) triethylamine in 60 ml DMF at room temperature. The reaction mixture was stirred for 16 hours at room temperature, the poured onto aq. sodium bicarbonate solution and extracted with ethylacetate. Purification of the crude product by flash chromatography gave 2.26 g (10.1 mmol, 59%) of 1-(4-chloro-benzyl)-3-methyl-piperazine as colorless oil. | CC1CN(Cc2ccc(Cl)cc2)CCN1 | null | 59.4 | null |
1,479,971 | ord_dataset-c3c1091f873b4f40827973a6f1f9b685 | null | 2014-01-01T00:09:00 | true | Br[C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[F:22])[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]([Cl:18])([F:17])[F:16])=[CH:10][CH:9]=1)=[O:6].[F:23][C:24]1[CH:25]=[N:26][NH:27][C:28]=1[Sn](CCCC)(CCCC)CCCC.C([O-])([O-])=O.[Na+].[Na+]>CS(C)=O.CCOC(C)=O.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:18][C:15]([F:17])([F:16])[O:14][C:11]1[CH:12]=[CH:13][C:8]([NH:7][C:5](=[O:6])[C:4]2[CH:19]=[CH:20][C:21]([F:22])=[C:2]([C:28]3[NH:27][N:26]=[CH:25][C:24]=3[F:23])[CH:3]=2)=[CH:9][CH:10]=1 | CCCC[Sn](CCCC)(CCCC)c1[nH]ncc1F | O=C(Nc1ccc(OC(F)(F)Cl)cc1)c1ccc(F)c(Br)c1 | null | c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1 | O=C([O-])[O-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CS(C)=O | CCOC(C)=O | null | null | null | null | null | null | null | null | null | 100 | 20 | A mixture of 3-bromo-N-(4-(chlorodifluoromethoxy)phenyl)-4-fluorobenzamide (Stage 20.2, 200 mg, 0.497 mmol), 4-fluoro-5-(tributylstannyl)-1H-pyrazole (211 mg, 0.472 mmol) and Pd(PPh3)4 (28.7 mg, 0.025 mmol) in DMSO (1.5 mL) in a sealed vial was stirred at 100° C. for 20 h under an argon atmosphere. The RM was diluted with EtOAc (30 mL), treated with sat. aq. Na2CO3 (20 mL) and extracted with EtOAc. The combined extracts were washed with water (20 mL) and brine (20 mL), dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give a crude product which was purified by flash chromatography (Silica gel column, 12 g, n-hexane/EtOAc 95:5 to 6:4) to give the title product as a white solid. HPLC (Condition 5) tR=7.20 min, UPLC-MS (Condition 3) tR=1.12 min, m/z=400.1 [M+H]+. | O=C(Nc1ccc(OC(F)(F)Cl)cc1)c1ccc(F)c(-c2[nH]ncc2F)c1 | null | null | null |
1,186,039 | ord_dataset-9cd817a75dfc4fe7ad19d4232772d5ff | null | 2012-01-01T00:07:00 | true | Cl[C:2]([O:4][C:5]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][CH:6]=1)=[O:3].[CH2:14]([CH:17]1[CH2:22][CH2:21][N:20](C(OC(C)(C)C)=O)[CH2:19][CH2:18]1)[C:15]#[CH:16]>>[CH2:14]([CH:17]1[CH2:22][CH2:21][N:20]([C:2]([O:4][C:5]2[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][CH:6]=2)=[O:3])[CH2:19][CH2:18]1)[C:15]#[CH:16] | C#CCC1CCN(C(=O)OC(C)(C)C)CC1 | O=C(Cl)Oc1ccc([N+](=O)[O-])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 | 4-(nitro)phenyl chloroformate (5.0 g, 24.8 mmol) was added to a solution of tert-butyl 4-(prop-2-ynyl)piperidine-1-carboxylate (4.25 g, 19.0 mmol) according to general procedure 1. Yield=5.72 g, 80%. m/z MH+=289.04. HPLC rt=10.4 min. | C#CCC1CCN(C(=O)Oc2ccc([N+](=O)[O-])cc2)CC1 | null | null | null |
1,478,662 | ord_dataset-c3c1091f873b4f40827973a6f1f9b685 | null | 2014-01-01T00:09:00 | true | [CH3:1][C:2]1[O:6][N:5]=[C:4]([O:7][CH:8]2[CH2:11][N:10]([C:12]3[N:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][C:13]=3[C:14]([O:16]C)=[O:15])[CH2:9]2)[CH:3]=1.O.[OH-].[Li+]>O1CCOCC1.O>[CH3:1][C:2]1[O:6][N:5]=[C:4]([O:7][CH:8]2[CH2:11][N:10]([C:12]3[N:21]=[CH:20][C:19]([C:22]([F:25])([F:23])[F:24])=[CH:18][C:13]=3[C:14]([OH:16])=[O:15])[CH2:9]2)[CH:3]=1 | COC(=O)c1cc(C(F)(F)F)cnc1N1CC(Oc2cc(C)on2)C1 | null | null | [Li+] | [OH-] | null | 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 | null | null | To a solution of methyl 2-(3-((5-methylisoxazol-3-yl)oxy)azetidin-1-yl)-5-(trifluoromethyl)nicotinate (D88) (20 mg, 0.056 mmol) in 1,4-dioxane/water (3 ml/1 ml), lithium hydroxide monohydrate (3.52 mg, 0.084 mmol) and the resulting mixture was heated at 130° C. under microwave irradiation 10 min (2 cycles of 5 min each). Solvents were evaporated in vacuo and the residue was taken in a mixture water/1M HCl (5 ml/15 ml) and extracted with ethyl acetate (3×20 ml). Collected organics, after solvent evaporation, afforded the title compound (D129) (19 mg) | Cc1cc(OC2CN(c3ncc(C(F)(F)F)cc3C(=O)O)C2)no1 | null | 98.8 | null |
1,097,178 | ord_dataset-af85e6f81c2d49f08086afd6d9e6959c | null | 2011-01-01T00:10:00 | true | [N:1]1[CH:6]=[CH:5][C:4]([CH2:7][NH:8][C:9]2[CH:28]=[CH:27][CH:26]=[CH:25][C:10]=2[C:11]([NH:13][O:14][CH2:15][C:16]2[CH:24]=[CH:23][C:19]([C:20](O)=[O:21])=[CH:18][CH:17]=2)=[O:12])=[CH:3][CH:2]=1.[CH3:29][N:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1>>[CH3:29][N:30]1[CH2:35][CH2:34][N:33]([C:20]([C:19]2[CH:18]=[CH:17][C:16]([CH2:15][O:14][NH:13][C:11](=[O:12])[C:10]3[CH:25]=[CH:26][CH:27]=[CH:28][C:9]=3[NH:8][CH2:7][C:4]3[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=3)=[CH:24][CH:23]=2)=[O:21])[CH2:32][CH2:31]1 | CN1CCNCC1 | O=C(O)c1ccc(CONC(=O)c2ccccc2NCc2ccncc2)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 | Prepared by a similar procedure as described for preparation of example 405. Starting materials: 4-{2-[(Pyridin-4-ylmethyl)-amino]-benzoylaminooxymethyl}-benzoic acid (see example 404) and 1-methylpiperazine. The title compound was crystallised from toluene. 13C-NMR (DMSO-d6) δ 168.6, 167.2, 149.5, 148.9, 148.2, 137.3, 135.7, 132.4, 128.7, 128.0, 126.8, 121.9, 114.8, 113.3, 111.4, 76.4, 54.4, 46.8, 45.5, 44.8. | CN1CCN(C(=O)c2ccc(CONC(=O)c3ccccc3NCc3ccncc3)cc2)CC1 | null | null | null |
736,539 | ord_dataset-76dd1b78ee414d2da0ed30700ef026f7 | null | 2006-01-01T00:10:00 | true | [NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7]([CH3:15])([CH3:14])[CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[N:6]=1.[Cl:16][C:17]1[CH:22]=[C:21]([Cl:23])[CH:20]=[C:19]([CH3:24])[C:18]=1[S:25](Cl)(=[O:27])=[O:26]>>[Cl:16][C:17]1[CH:22]=[C:21]([Cl:23])[CH:20]=[C:19]([CH3:24])[C:18]=1[S:25]([NH:1][C:2]1[S:3][CH:4]=[C:5]([C:7]([CH3:14])([CH3:15])[CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[N:6]=1)(=[O:27])=[O:26] | Cc1cc(Cl)cc(Cl)c1S(=O)(=O)Cl | CCOC(=O)CC(C)(C)c1csc(N)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 title compound was prepared from ethyl 3-(2-amino-1,3-thiazol-4-yl)-3-methylbutanoate (METHOD I) and 2,4-dichloro-6-methylbenzenesulfonyl chloride as described in the synthetic method to give a white solid (55.0 mg) with purity >90%. MS (pos) m/z 451.2, 453.2. | CCOC(=O)CC(C)(C)c1csc(NS(=O)(=O)c2c(C)cc(Cl)cc2Cl)n1 | null | null | null |
109,864 | ord_dataset-406d20cb3f314e2c967b14f55925f895 | null | 1983-01-01T00:10:00 | true | [CH2:1]([N:3]1[CH2:7][C:6](O[Si](C)(C)C)=[C:5](O[Si](C)(C)C)[CH2:4]1)[CH3:2].Cl.Cl.[NH2:20][CH2:21][C:22]([NH2:24])=[NH:23]>>[CH2:1]([N:3]1[CH2:7][C:6]2[C:5](=[N:23][C:22]([NH2:24])=[CH:21][N:20]=2)[CH2:4]1)[CH3:2] | N=C(N)CN | CCN1CC(O[Si](C)(C)C)=C(O[Si](C)(C)C)C1 | null | Cl | 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 | This compound was prepared analogous to Example 22 from 1-ethyl-2,5-dihydro-3,4-bis(trimethylsilyloxy)-pyrrole and α-amino-acetamidine dihydrochloride. | CCN1Cc2ncc(N)nc2C1 | null | null | null |
1,019,989 | ord_dataset-f024e9664ab64906a71a2ff6004cb3d0 | null | 2010-01-01T00:12:00 | true | [Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:11]([NH2:13])=[O:12])[CH:10]=1)[NH:7][CH:6]=[C:5]2[CH:14]1[CH2:19][CH2:18][N:17]([S:20]([CH:23]=[CH2:24])(=[O:22])=[O:21])[CH2:16][CH2:15]1.[CH3:25][O-:26].[Na+]>CO>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:11]([NH2:13])=[O:12])[CH:10]=1)[NH:7][CH:6]=[C:5]2[CH:14]1[CH2:19][CH2:18][N:17]([S:20]([CH2:23][CH2:24][O:26][CH3:25])(=[O:22])=[O:21])[CH2:16][CH2:15]1 | C=CS(=O)(=O)N1CCC(c2c[nH]c3c(C(N)=O)cc(Br)cc23)CC1 | C[O-] | null | [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 | 80 | 1 | The mixture of 5-bromo-3-[1-(ethenylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide (150 mg, 0.36 mmol), sodium methoxide in methanol (25%, 1.0 mL) and methanol (2.0 mL) was stirred at 80° C. for 1 hr. After which time the reaction mixture was concentrated under reduced pressure. The residue was purified by combiflash to give the title compound (100.0 mg, 63%). | COCCS(=O)(=O)N1CCC(c2c[nH]c3c(C(N)=O)cc(Br)cc23)CC1 | null | 63 | null |
1,011,397 | ord_dataset-7448b89163bf426c9d9777809ce24cec | null | 2010-01-01T00:11:00 | true | [CH:1]([C:3]1[O:7][C:6]([B:8]([OH:10])[OH:9])=[CH:5][CH:4]=1)=O.[CH3:11][NH:12][CH3:13]>COCCOC.C1COCC1>[CH3:11][N:12]([CH2:1][C:3]1[O:7][C:6]([B:8]([OH:10])[OH:9])=[CH:5][CH:4]=1)[CH3:13] | CNC | O=Cc1ccc(B(O)O)o1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | COCCOC | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | 0.08 | To a solution of (5-formyl-2-furyl)boronic acid (50 mg, 0.36 mmol) in DME (1.0 mL) was added a 2.0M solution of dimethylamine in THF (0.53 mL, 1.0 mmol). The reaction mixture stirred for 5 minutes before resin bound MP-BH(OAc)3 (2.2 mmol/g, 0.33 g, 0.714 mmol) was added. The reaction mixture was stirred at room temperature for five hours and an additional 1 equivalent of dimethylamine in THF was added and stirring continued overnight. The reaction mixture was filtered through a plug of glass wool and the resin was washed with DME. The THF/DME filtrate solution containing the desired compound was used immediately in subsequent reactions. | CN(C)Cc1ccc(B(O)O)o1 | null | null | null |
1,636,106 | ord_dataset-f0794d5ded7a4d3fab45cc3d7a89ee3d | null | 2015-01-01T00:09:00 | true | [CH3:1][C:2]1([CH3:28])[CH2:5][CH:4]([CH:6]([NH:16][C:17]2[C:26]([CH3:27])=[CH:25][C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[N:18]=2)[C:7]2[CH:15]=[CH:14][C:10]([C:11](O)=[O:12])=[CH:9][CH:8]=2)[CH2:3]1.Cl.CN(C)CCCN=C=NCC.Cl.[CH3:42][O:43][C:44](=[O:48])[CH2:45][CH2:46][NH2:47].C(N(CC)CC)C>ClCCl>[CH3:42][O:43][C:44](=[O:48])[CH2:45][CH2:46][NH:47][C:11](=[O:12])[C:10]1[CH:14]=[CH:15][C:7]([CH:6]([CH:4]2[CH2:3][C:2]([CH3:1])([CH3:28])[CH2:5]2)[NH:16][C:17]2[C:26]([CH3:27])=[CH:25][C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[N:18]=2)=[CH:8][CH:9]=1 | Cc1cc2ccccc2nc1NC(c1ccc(C(=O)O)cc1)C1CC(C)(C)C1 | COC(=O)CCN | null | CCN=C=NCCCN(C)C | Cl | 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 | null | null | (+/−)-4-[(3,3-dimethyl-cyclobutyl)-(3-methyl-quinolin-2-ylamino)-methyl]-benzoic acid (Intermediate 26, 1.0 eq.), 1-hydrobenzotriazole hydrate (1.2 eq.), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (1.2 eq.), beta-alanine methyl ester hydrochloride (1.1 eq.), and triethylamine (1.3 eq.) were combined in anhydrous dichloromethane in a similar manner as described in the experimental for intermediate 27 to provide (+/−)-3-{4-[(3,3-dimethyl-cyclobutyl)-(3-methyl-quinolin-2-ylamino)-methyl]-benzoylamino}-propionic acid methyl ester which was resolved via chiral chromatography to provide the title compound. Preparative chiral SFC: (Chiralpak AD-H column, 21 mm×25 cm, 40% methanol/carbon dioxide eluent, 0.2% isopropylamine modifier, 65.0 mL/min flow rate, 2.71 retention time); 1H NMR (400 MHz, CDCl3) δ 7.63-7.69 (m, 2H), 7.58 (t, J=3.9 Hz, 2H), 7.45-7.51 (m, 3H), 7.41 (ddd, J=8.4, 7.0, 1.6 Hz, 1H), 7.14 (ddd, J=8.0, 6.9, 1.2 Hz, 1H), 6.72 (t, J=6.0 Hz, 1H), 5.31 (dd, J=9.7, 6.7 Hz, 1H), 4.75 (d, J=6.8 Hz, 1H), 3.69 (q, J=6.2 Hz, 5H), 2.55-2.71 (m, 3H), 2.28 (d, J=0.8 Hz, 3H), 1.95 (ddd, J=11.2, 8.0, 3.0 Hz, 1H), 1.78 (dd, J=11.1, 9.0 Hz, 1H), 1.64-1.72 (m, 2H), 1.15 (s, 3H), 1.08 (s, 3H); MS (M+1): 460.4. | COC(=O)CCNC(=O)c1ccc(C(Nc2nc3ccccc3cc2C)C2CC(C)(C)C2)cc1 | null | null | null |
1,703,114 | ord_dataset-54347fcace774f89850681d6dec8009f | null | 2016-01-01T00:03:00 | true | [CH3:1][S:2](Cl)(=[O:4])=[O:3].[NH:6]1[CH2:10][CH2:9][C@H:8]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH2:7]1.CCN(CC)CC>C(Cl)Cl>[CH3:1][S:2]([N:6]1[CH2:10][CH2:9][C@H:8]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:16])([CH3:15])[CH3:17])[CH2:7]1)(=[O:4])=[O:3] | CC(C)(C)OC(=O)N[C@H]1CCNC1 | CS(=O)(=O)Cl | 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 | null | 2 | Methane sulfonyl chloride (204 mg, 1.78 mmol) was added to a solution of (S)-tert-butyl pyrrolidin-3-ylcarbamate (300 mg, 1.62 mmol) and Et3N (197 mg, 1.94 mmol) in DCM (6 mL) at 0-5° C.; stirring was continued at 20-35° C. for 2 h. The reaction mixture was diluted with DCM, washed with water, aqueous NaHCO3 solution followed by brine to afford 250 mg of the title compound. | CC(C)(C)OC(=O)N[C@H]1CCN(S(C)(=O)=O)C1 | null | 58.4 | null |
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