original_index int64 2 1.77M | agent_000 stringlengths 1 540 ⌀ | agent_001 stringlengths 1 852 ⌀ | agent_002 stringlengths 1 247 ⌀ | date_of_experiment timestamp[ns]date | extracted_from_file stringclasses 489 values | grant_date timestamp[ns]date 1976-01-01 00:01:00 2016-01-01 00:09:00 | is_mapped bool 1 class | procedure_details stringlengths 8 24.5k | product_000 stringlengths 1 484 | product_001 stringlengths 1 208 ⌀ | reactant_000 stringlengths 1 902 | reactant_001 stringlengths 1 902 ⌀ | reactant_002 stringlengths 1 285 ⌀ | rxn_str stringlengths 87 6.12k | rxn_time float64 0 2.16k ⌀ | solvent_000 stringclasses 446 values | solvent_001 stringclasses 405 values | solvent_002 stringclasses 330 values | temperature float64 -230 30.1k ⌀ | yield_000 float64 0 90,205,156,600B ⌀ | yield_001 float64 0 100M ⌀ | 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_003 null | solvent_004 null | solvent_005 null | solvent_006 null | solvent_007 null | solvent_008 null | solvent_009 null | solvent_010 null |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1,704,561 | O=C[O-] | [NH4+] | null | null | ord_dataset-54347fcace774f89850681d6dec8009f | 2016-01-01T00:03:00 | true | A mixture of benzyl ((3R,4R)-4-fluoro-1-(9-isopropyl-6-((1-methyl-1H-pyrazol-4-yl)amino)-9H-purin-2-yl)pyrrolidin-3-yl)carbamate (390 mg, 0.8 mmol), ammonium formate (514 mg, 8 mmol) in ethanol (20 mL) was degassed for 3 min and 10%-Pd/C (50 mg) was then added. The reaction was stirred and heated to gentle reflux for 45 min. The catalyst was removed by filtration and washed well with ethanol (40 mL). The combined liquors were concentrated to give a residue, which was taken into water (5 mL) and extracted with DCM-isopropanol (9:1, 2×70 mL). The combined organic extracts were washed with saturated NaHCO3 (5 mL), dried over Na2SO4 and evaporated to give the title compound as a light yellow solid (272 mg, 96% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.58 (s, 1 H) 8.00 (s, 2 H) 7.90 (s, 2 H) 7.73 (s, 1 H) 4.89-5.08 (m, 1 H) 4.56-4.66 (m, 1 H) 3.86-4.00 (m, 1 H) 3.81-3.85 (m, 3 H) 3.58-3.80 (m, 3 H) 3.53 (d, J=11.13 Hz, 1 H) 1.51 (d, J=6.72 Hz, 6 H). 19F NMR (376 MHz, DMSO-d6) δ ppm −177.42 (s, 1F). m/z (APCI+) for C16H22FN9 360.2 (M+H)+. Chiral purity was determined as below (using racemic sample to compare): | CC(C)n1cnc2c(Nc3cnn(C)c3)nc(N3C[C@@H](N)[C@H](F)C3)nc21 | null | CC(C)n1cnc2c(Nc3cnn(C)c3)nc(N3C[C@@H](F)[C@H](NC(=O)OCc4ccccc4)C3)nc21 | null | null | [F:1][C@@H:2]1[CH2:6][N:5]([C:7]2[N:15]=[C:14]3[C:10]([N:11]=[CH:12][N:13]3[CH:16]([CH3:18])[CH3:17])=[C:9]([NH:19][C:20]3[CH:21]=[N:22][N:23]([CH3:25])[CH:24]=3)[N:8]=2)[CH2:4][C@H:3]1[NH:26]C(=O)OCC1C=CC=CC=1.C([O-])=O.[NH4+].O>C(O)C>[NH2:26][C@H:3]1[C@H:2]([F:1])[CH2:6][N:5]([C:7]2[N:15]=[C:14]3[C:10]([N:11]=[CH:12][N:13]3[CH:16]([CH3:18])[CH3:17])=[C:9]([NH:19][C:20]3[CH:21]=[N:22][N:23]([CH3:25])[CH:24]=3)[N:8]=2)[CH2:4]1 | null | CCO | O | null | null | null | 94.6 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,488,457 | [Pd] | [NH4+] | [OH-] | null | ord_dataset-c3c1091f873b4f40827973a6f1f9b685 | 2014-01-01T00:09:00 | true | A solution of 1-(4-chloro-pyrrolo[2,3-d]pyrimidin-7-yl)-cyclopropanecarboxylic acid methyl ester (Preparation 245, 920 mg, 3.65 mmol) in ethanol (20 mL) was degassed with argon for 15 min. Ammonium hydroxide (4 mL) and 10% palladium on charcoal were added and the reaction mixture was stirred at room temperature under hydrogen (balloon pressure) for 5 hours. The reaction mixture was filtered on a celite bed, washed with ethanol (2×10 mL) and the filtrate was evaporated in vacuo. The crude material was purified by column chromatography on silica gel (gradient of DCM:methanol 100:0 to 98:2) to afford the title compound as a gum in 59% yield, 470 mg. | COC(=O)C1(n2ccc3cncnc32)CC1 | null | COC(=O)C1(n2ccc3c(Cl)ncnc32)CC1 | null | null | [CH3:1][O:2][C:3]([C:5]1([N:8]2[C:12]3[N:13]=[CH:14][N:15]=[C:16](Cl)[C:11]=3[CH:10]=[CH:9]2)[CH2:7][CH2:6]1)=[O:4].[OH-].[NH4+]>C(O)C.[Pd]>[CH3:1][O:2][C:3]([C:5]1([N:8]2[C:12]3[N:13]=[CH:14][N:15]=[CH:16][C:11]=3[CH:10]=[CH:9]2)[CH2:6][CH2:7]1)=[O:4] | 5 | CCO | null | null | 25 | 59 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
786,033 | O=C([O-])[O-] | [Br-] | [Cs+] | null | ord_dataset-4ad5db8537994579bef51f16dd8bf0bd | 2007-01-01T00:08:00 | true | Phenol (0.518 g, 5.5 mmol) is combined with anhydrous acetonitrile (20 mL) and cesium carbonate (2.3 g, 10 mmol) and allowed to stir at room temperature under nitrogen. To the reaction is added 4-bromomethyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carboxylic acid ethyl ester (1.97 g, 5.00 mmol). The reaction is monitored by TLC until all of the bromide is consumed. The reaction is diluted with ethyl ether (100 mL), then o.1N NaOH (50 mL) is added. The two phases are separated, then the organic layer is washed with water (50 mL) and brine (50 mL). The organic layer is dried over anhydrous sodium sulfate, then concentrated. The material is further purified using flash chromatography to yield 1.75 g or 86% yield of the product. | CCOC(=O)c1sc(-c2ccc(C(F)(F)F)cc2)nc1COc1ccccc1 | null | CCOC(=O)c1sc(-c2ccc(C(F)(F)F)cc2)nc1CBr | Oc1ccccc1 | null | [C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:14]([O:16][C:17]([C:19]1[S:23][C:22]([C:24]2[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][CH:25]=2)=[N:21][C:20]=1[CH2:34]Br)=[O:18])[CH3:15].[Br-]>C(#N)C>[CH2:14]([O:16][C:17]([C:19]1[S:23][C:22]([C:24]2[CH:29]=[CH:28][C:27]([C:30]([F:32])([F:33])[F:31])=[CH:26][CH:25]=2)=[N:21][C:20]=1[CH2:34][O:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)=[O:18])[CH3:15] | null | CC#N | null | null | 25 | null | 86 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
753,699 | O=C([O-])[O-] | [Cs+] | null | null | ord_dataset-844a22e1fcab44a5b59c5e2922b2855a | 2007-01-01T00:01:00 | true | Stir at 50° C. for 10 min. a mixture of 3-(4-pyridinylamino)-1H-indole-2-carboxylic acid (1.27 g, 5 mmol) in DMF (25 mL), and add Cs2CO3 (1.63 g, 5 mmol). After 10 min. add bromomethyl acetate (0.95 g, 6.21 mmol) and one minute thereafter quench into aqueous NH4Cl solution. Extract with EtOAc and wash the extract with aqueous NaHCO3 solution. Dry the extract (MgSO4), filter and concentrate under vacuum to give a solid. Triturate the solid with EtOAc and obtain the title compound as a solid: MS 326(M+H). | CC(=O)OCOC(=O)c1[nH]c2ccccc2c1Nc1ccncc1 | null | CC(=O)OCBr | O=C(O)c1[nH]c2ccccc2c1Nc1ccncc1 | null | [N:1]1[CH:6]=[CH:5][C:4]([NH:7][C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[NH:10][C:9]=2[C:17]([OH:19])=[O:18])=[CH:3][CH:2]=1.C([O-])([O-])=O.[Cs+].[Cs+].[C:26]([O:29][CH2:30]Br)(=[O:28])[CH3:27]>CN(C=O)C>[C:26]([O:29][CH2:30][O:18][C:17]([C:9]1[NH:10][C:11]2[C:16]([C:8]=1[NH:7][C:4]1[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=1)=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:19])(=[O:28])[CH3:27] | 0.17 | CN(C)C=O | null | null | 50 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
588,681 | [Pt] | null | null | null | ord_dataset-7a74d48eeefd45aba53e7258f3ae067a | 2003-01-01T00:04:00 | true | N-(4-Chloro-3-methyl-5-isothiazolyl)-4-hydroxy-3-nitrophenylacetamide (374 g, 0.114 mol) was hydrogenated at 15 bar over a 3% w/w platinum on carbon catalyst (15 g) in N,N-dimethylformamide (180 ml). Once the reduction was complete, the catalyst was removed by filtration and the filtrate was evaporated in vacuo to give N-(4-chloro-3-methyl-5-isothiazolyl)-3-amino-4-hydroxyphenylacetamide (26.8 g) as a pale brown solid, which used without further purification in the next step. | Cc1nsc(NC(=O)Cc2ccc(O)c(N)c2)c1Cl | null | Cc1nsc(NC(=O)Cc2ccc(O)c([N+](=O)[O-])c2)c1Cl | null | null | [Cl:1][C:2]1[C:3]([CH3:21])=[N:4][S:5][C:6]=1[NH:7][C:8](=[O:20])[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([OH:16])=[C:12]([N+:17]([O-])=O)[CH:11]=1>[Pt].CN(C)C=O>[Cl:1][C:2]1[C:3]([CH3:21])=[N:4][S:5][C:6]=1[NH:7][C:8](=[O:20])[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([OH:16])=[C:12]([NH2:17])[CH:11]=1 | null | CN(C)C=O | null | null | null | null | 79 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
979,306 | O=[Os](=O)(=O)=O | [Na+] | null | null | ord_dataset-f886e51ba1484c76a94bce1482f1eab9 | 2010-01-01T00:07:00 | true | A commercial 4% w/w solution of osmium tetraoxide (10 mL, 0.82 mmol, 0.005 eq) was added to a stirred mixture of 4-allyloxy-7a-methyl-hexahydro-indene-1,5-dione (36.4 g, 164 mmol), 2,6-lutidine (57.2 mL, 246 mmol, 1.5 eq) and sodium periodate (210.6 g, 492 mmol, 3 eq) in dioxane (900 mL) and water (300 mL) at 0° C. The reaction mixture was then allowed to warm slowly to room temperature, and stirred for 24 h. The reaction mixture was cooled to 0° C., and then filtered through a fritted funnel. DCM (1 L) was used to wash to salt cake, and the filtrate was used to extract the separated aqueous solution (4×250 mL). The combined organic layer was dried with magnesium sulfate. The resulting mixture was filtered, condensed and the resulting residue purified by flash chromatography using 20-90% ethyl acetate in hexane yield the title compound as a light yellow foam. | CC12CCC(=O)C(OCC=O)C1CCC2=O | null | [O-][I+3]([O-])([O-])[O-] | C=CCOC1C(=O)CCC2(C)C(=O)CCC12 | null | [CH2:1]([O:4][CH:5]1[C:13](=[O:14])[CH2:12][CH2:11][C:10]2([CH3:15])[CH:6]1[CH2:7][CH2:8][C:9]2=[O:16])[CH:2]=C.N1C(C)=CC=CC=1C.I([O-])(=O)(=O)=[O:26].[Na+]>O1CCOCC1.O.[Os](=O)(=O)(=O)=O>[CH3:15][C:10]12[C:9](=[O:16])[CH2:8][CH2:7][CH:6]1[CH:5]([O:4][CH2:1][CH:2]=[O:26])[C:13](=[O:14])[CH2:12][CH2:11]2 | 24 | C1COCCO1 | Cc1cccc(C)n1 | O | 25 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
910,920 | Br | null | null | null | ord_dataset-c663259b80f947e2a8923796fb0e9a6b | 2009-01-01T00:10:00 | true | To N-[6-(4-fluorobenzyl)-4-methoxy-2-methyl-3,5-dioxo-2,3,5,6,7,8-hexahydro-2,6-naphthyridin-1-yl]-N-methylacetamide (0.070 g, 0.181 mmol) was dissolved in 1 mL glacial acetic acid and 0.75 mL 30% by weight HBr in acetic acid solution was added. The reaction was stirred for 1.5 hours, water was added and the reaction evaporated to dryness under vacuum. The residue was purified on reverse phase and the fractions collected and evaporated. The residue was dissolved in dioxane, from which crystals formed and were collected. The crystals were dried under vacuum with heat to give the product. | CC(=O)N(C)c1c2c(c(O)c(=O)n1C)C(=O)N(Cc1ccc(F)cc1)CC2 | null | COc1c2c(c(N(C)C(C)=O)n(C)c1=O)CCN(Cc1ccc(F)cc1)C2=O | null | null | [F:1][C:2]1[CH:28]=[CH:27][C:5]([CH2:6][N:7]2[CH2:16][CH2:15][C:14]3[C:9](=[C:10]([O:24]C)[C:11](=[O:23])[N:12]([CH3:22])[C:13]=3[N:17]([CH3:21])[C:18](=[O:20])[CH3:19])[C:8]2=[O:26])=[CH:4][CH:3]=1.Br.O>C(O)(=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]2[CH2:16][CH2:15][C:14]3[C:9](=[C:10]([OH:24])[C:11](=[O:23])[N:12]([CH3:22])[C:13]=3[N:17]([CH3:21])[C:18](=[O:20])[CH3:19])[C:8]2=[O:26])=[CH:27][CH:28]=1 | 1.5 | O | CC(=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 |
608,384 | O=C([O-])Cl | [K+] | null | null | ord_dataset-73916d628db147c89020b3baac642d48 | 2003-01-01T00:09:00 | true | The preparation was carried out as in Example 2 but using 250 g of ethylene carbonate, 90 g (1.55 mol) of potassium fluoride and 162.6 g (1.0 mol) of cyclohexyl chloroformate. After addition of the chloroformate, stirring of the mixture was continued for 45 minutes at 45° C. Evaporation under vacuum was carried out as above. By distillation under reduced pressure, 122.7 g (84% yield) of cyclohexyl fluoroformate with a boiling point of 55-56° C. at 22 mm Hg were obtained. | O=C(F)OC1CCCCC1 | null | O=C(Cl)OC1CCCCC1 | [F-] | null | C1(=O)OCCO1.[F-:7].[K+].Cl[C:10]([O:12][CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)=[O:11].ClC([O-])=O>>[F:7][C:10]([O:12][CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)=[O:11] | 0.75 | O=C1OCCO1 | null | null | null | null | 83.9 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,113,509 | CN(C)C(On1nnc2ccccc21)=[N+](C)C | F[P-](F)(F)(F)(F)F | null | null | ord_dataset-375a420ee9b042918ddca20f02df37d3 | 2011-01-01T00:11:00 | true | A mixture of 3-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]benzoic acid (69 mg), 1,1-dimethylethyl (2S)-4-{[3′-(aminomethyl)-3-biphenylyl]methyl}-2-methyl-1-piperazinecarboxylate (60 mg), HBTU (68 mg) and diisopropyl ethyl amine (112.5 μL) in DCM (5 mL) and THF (1 mL) were stirred at room temperature overnight. It was concentrated. Separation via CombiFlash then afforded the desired product (33 mg). | CCc1nc2c(cnn2CC)c(NC2CCOCC2)c1CNC(=O)c1cccc(C(=O)NCc2cccc(-c3cccc(CN4CCN(C(=O)OC(C)(C)C)[C@@H](C)C4)c3)c2)c1 | null | C[C@H]1CN(Cc2cccc(-c3cccc(CN)c3)c2)CCN1C(=O)OC(C)(C)C | CCc1nc2c(cnn2CC)c(NC2CCOCC2)c1CNC(=O)c1cccc(C(=O)O)c1 | null | [CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:32][CH3:33])=[C:10]([CH2:19][NH:20][C:21]([C:23]3[CH:24]=[C:25]([CH:29]=[CH:30][CH:31]=3)[C:26](O)=[O:27])=[O:22])[C:11]([NH:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2].[NH2:34][CH2:35][C:36]1[CH:37]=[C:38]([C:42]2[CH:47]=[CH:46][CH:45]=[C:44]([CH2:48][N:49]3[CH2:54][CH2:53][N:52]([C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])[C@@H:51]([CH3:62])[CH2:50]3)[CH:43]=2)[CH:39]=[CH:40][CH:41]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>C(Cl)Cl.C1COCC1>[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:32][CH3:33])=[C:10]([CH2:19][NH:20][C:21]([C:23]3[CH:24]=[C:25]([C:26]([NH:34][CH2:35][C:36]4[CH:37]=[C:38]([C:42]5[CH:47]=[CH:46][CH:45]=[C:44]([CH2:48][N:49]6[CH2:54][CH2:53][N:52]([C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])[C@@H:51]([CH3:62])[CH2:50]6)[CH:43]=5)[CH:39]=[CH:40][CH:41]=4)=[O:27])[CH:29]=[CH:30][CH:31]=3)=[O:22])[C:11]([NH:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2] | 8 | C1CCOC1 | CCN(C(C)C)C(C)C | ClCCl | 25 | 26.2 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,576,890 | [N-]=O | [NH-]O | null | null | ord_dataset-9741bb5fd93044078df2a45f45733054 | 2015-01-01T00:04:00 | true | Coupling of (S)-1-benzyl-5-oxopyrrolidine-2-carboxylic acid with 3-amino-2-hydroxy-4-phenylbutanamide was followed by oxidation of the resulting hydroxyamide intermediate to the corresponding ketoamide. | NC(=O)C(=O)C(Cc1ccccc1)NC(=O)[C@@H]1CCC(=O)N1Cc1ccccc1 | null | NC(=O)C(O)C(N)Cc1ccccc1 | O=C(O)[C@@H]1CCC(=O)N1Cc1ccccc1 | null | [CH2:1]([N:8]1[C:12](=[O:13])[CH2:11][CH2:10][C@H:9]1[C:14]([OH:16])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:17][CH:18]([CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH:19]([OH:23])[C:20]([NH2:22])=[O:21].O[NH-].O=[N-]>>[NH2:22][C:20](=[O:21])[C:19](=[O:23])[CH:18]([NH:17][C:14]([C@@H:9]1[CH2:10][CH2:11][C:12](=[O:13])[N:8]1[CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:16])[CH2:24][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
839,737 | Cl | [Li+] | [OH-] | null | ord_dataset-074f86301ec5441ab3b52d902ac06949 | 2008-01-01T00:09:00 | true | To a solution of 5-tert-Butoxycarbonylamino-2-tert-butoxycarbonylmethyl-2H-pyrazole-3-carboxylic acid methyl ester (0.5 gm) dissolved in 25 ml of tetrahydrofuran was added 5 ml of 1M lithium hydroxide. After stirring the reaction mixture at 60 C for 2 hours, 1N hydrochloric acid was added and the product extracted with dichloromethane. The extract was dried over magnesium sulfate, filtered and evaporated to obtain 0.49 gm of title product. ESI M+1=286. | CC(C)(C)OC(=O)Nc1cc(C(=O)O)n(CC(=O)O)n1 | null | COC(=O)c1cc(NC(=O)OC(C)(C)C)nn1CC(=O)OC(C)(C)C | null | null | C[O:2][C:3]([C:5]1[N:6]([CH2:18][C:19]([O:21]C(C)(C)C)=[O:20])[N:7]=[C:8]([NH:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH:9]=1)=[O:4].[OH-].[Li+].Cl>O1CCCC1>[C:14]([O:13][C:11]([NH:10][C:8]1[CH:9]=[C:5]([C:3]([OH:4])=[O:2])[N:6]([CH2:18][C:19]([OH:21])=[O:20])[N:7]=1)=[O:12])([CH3:17])([CH3:15])[CH3:16] | 2 | C1CCOC1 | null | null | null | null | 122.1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,682,523 | null | null | null | null | ord_dataset-3953983e052a4076aa7cc0880b79cb8b | 2016-01-01T00:01:00 | true | A stirred solution of 2-(2-(2-(2,5-Dichloropyrimidin-4-yl)ethyl)phenyl)propanamide (A30) (0.120 g, 0.370 mmol), tert-butyl 4-(4-amino-1H-pyrazol-1-yl)piperidine-1-carboxylate (0.177 g, 0.666 mmol) in n-butanol (3 mL) and glacial acetic acid (0.004 mL, 0.074 mmol) was stirred at 150° C. in the microwave for 30 minutes. After cooling, the solvent was removed to afford a crude purple oil which was purified by silica gel column chromatography (Combiflash Rf, 0-30% MeOH in DCM) to give the title compound A32 as a red oil (0.090 g, 44% yield). LCMS-C: rt 5.44 min; m/z 554 [M+H]+. | CC(C(N)=O)c1ccccc1CCc1nc(Nc2cnn(C3CCN(C(=O)OC(C)(C)C)CC3)c2)ncc1Cl | null | CC(C)(C)OC(=O)N1CCC(n2cc(N)cn2)CC1 | CC(C(N)=O)c1ccccc1CCc1nc(Cl)ncc1Cl | null | Cl[C:2]1[N:7]=[C:6]([CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH:16]([CH3:20])[C:17]([NH2:19])=[O:18])[C:5]([Cl:21])=[CH:4][N:3]=1.[NH2:22][C:23]1[CH:24]=[N:25][N:26]([CH:28]2[CH2:33][CH2:32][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:30][CH2:29]2)[CH:27]=1.C(O)(=O)C>C(O)CCC>[NH2:19][C:17](=[O:18])[CH:16]([C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=1[CH2:9][CH2:8][C:6]1[C:5]([Cl:21])=[CH:4][N:3]=[C:2]([NH:22][C:23]2[CH:24]=[N:25][N:26]([CH:28]3[CH2:29][CH2:30][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:32][CH2:33]3)[CH:27]=2)[N:7]=1)[CH3:20] | null | CCCCO | CC(=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 |
391,988 | null | null | null | null | ord_dataset-4bc8addcf9cf4845817557760d62d5b5 | 1998-01-01T00:02:00 | true | Water (9 ml) and N,N'-dimethylethylenediamine (0.8 ml, 7.7 mmol) were added to 6-amino-4,5-dichloro-2-methyl-3(2H)-pyridazinone (500 mg, 2.6 mmol) as described in Chemical Pharmaceutical Bulletin, 30, 832 (1982), and the mixture was refluxed under heating for 3 hours. The reaction mixture was concentrated, added with chloroform, washed with water and brine and dried over anhydrous sodium sulfate. The solvent was distilled away and the residue obtained was subjected to silica gel column chromatography (chloroform:methanol=40:1) to give 448 mg of 8-amino-1,2,3,4-tetrahydro-1,4,6-trimethylpyrazino[2,3-d]pyridazin-5(6H)-one. | CN1CCN(C)c2c1c(N)nn(C)c2=O | null | Cn1nc(N)c(Cl)c(Cl)c1=O | CNCCNC | null | O.[CH3:2][NH:3][CH2:4][CH2:5][NH:6][CH3:7].[NH2:8][C:9]1[C:10](Cl)=[C:11](Cl)[C:12](=[O:16])[N:13]([CH3:15])[N:14]=1.C(Cl)(Cl)Cl>CO>[NH2:8][C:9]1[C:10]2[N:3]([CH3:2])[CH2:4][CH2:5][N:6]([CH3:7])[C:11]=2[C:12](=[O:16])[N:13]([CH3:15])[N:14]=1 | null | CO | ClC(Cl)Cl | O | null | null | 82.3 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,203,456 | null | null | null | null | ord_dataset-fb72428f30234761b4216139dc228d0c | 2012-01-01T00:09:00 | true | Intermediate 111 was coupled with 2-(3,5-difluoro-phenyl)-ethylamine following procedure F. The resulting product was deprotected following procedure G2. LC-MS showed the product had the expected M+H+ of 425. 1H NMR (Varian 300 MHz, CD3OD, shifts relative to the solvent peak at 3.3 ppm) δ 8.72 (s, 1H), 8.36 (t, 2H), 7.97 (d, 1H), 7.73 (d, 1H), 7.69 (d, 1H), 7.01 (d, 2H), 6.72 (s, 1H), 4.43 (d, 1H), 4.05 (m, 3H), 3.55 (m, 6H), 3.39 (m, 1H), 3.06 (t, 2H), 1.77 (d, 3H). | C[C@@H]1CNCCN1Cc1cccc(-c2ccnc(NCCc3cc(F)cc(F)c3)n2)c1 | null | CC1CN(C(=O)OC(C)(C)C)CCN1Cc1cccc(-c2ccnc(Cl)n2)c1 | NCCc1cc(F)cc(F)c1 | null | C(OC([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]3[CH:26]=[CH:25][N:24]=[C:23](Cl)[N:22]=3)[CH:16]=2)[CH:10]([CH3:28])[CH2:9]1)=O)(C)(C)C.[F:29][C:30]1[CH:31]=[C:32]([CH2:37][CH2:38][NH2:39])[CH:33]=[C:34]([F:36])[CH:35]=1>>[F:29][C:30]1[CH:31]=[C:32]([CH2:37][CH2:38][NH:39][C:23]2[N:22]=[C:21]([C:17]3[CH:18]=[CH:19][CH:20]=[C:15]([CH2:14][N:11]4[CH2:12][CH2:13][NH:8][CH2:9][C@H:10]4[CH3:28])[CH:16]=3)[CH:26]=[CH:25][N:24]=2)[CH:33]=[C:34]([F:36])[CH:35]=1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
274,081 | c1ccc(P(c2ccccc2)c2ccccc2)cc1 | null | null | null | ord_dataset-ee287d49cb8642e59ae9c3951f746312 | 1993-01-01T00:08:00 | true | A flask was charged with (S)-1-[(tert-Butyldiphenylsilyl)oxy]-3-butyn-2-ol (1) (1.30 g, 4 mmol), triphenylphosphine (2.52 g, 9.60 mmol), THF (30 mL), pyridine (360 mg, 4.56 mmol). To this mixture was added carbon tetrabromide (1.53 g, 4.60 mmol) in THF (10 ml) over a 5 minute period. The resulting reaction mixture was stirred for 45 minutes. Hexanes (50 mL) was added, and the mixture was filtered and concentrated in vacuo. The residue was taken up into hexanes (50 mL), washed with 1 M HCl (40 mL), saturated NaCl (40 mL). The organic extracts were dried (MgSO4) and concentrated by rotary evaporation to yield a yellow oil. Purification by flash silica gel chromatography (98:02 hexane/EtOAc) afforded (R)-2-bromo-1-[tert-butyldiphenylsilyloxy]-3-butyne (4) (1.50 g, 97%) as a colorless oil (Note: this material is unstable and should be used immediately): Rf 0.74 (90:10 hexane/EtOAc); IR (neat) 3308, 1437, 1112, 701 cm-1 ; 1H NMR (CDCl3) δ 7.70 (m, 4 H), 7.42 (m, 6 H), 4.46 (dt, J1 =6.66 Hz, J2 =2.36 Hz, 1 H), 3.91 (ddd, J1 =10.7 Hz, J2 =6.32, Hz, J3 =3.78 Hz, 2H), 2.59 (d, J=2.4 Hz, 2 H), 1.08 (m, 9H); 13C NMR (CDCl3); δ 135.8, 132.8, 129.6, 127.6, 80.3, 75.6, 67.5, 36.2, 26.8, 19.3. ##STR19## | C#C[C@@H](Br)CO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C | null | C#C[C@H](O)CO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C | BrC(Br)(Br)Br | null | [Si:1]([O:18][CH2:19][C@@H:20](O)[C:21]#[CH:22])([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N1C=CC=CC=1.C(Br)(Br)(Br)[Br:50]>C1COCC1>[Br:50][C@H:20]([C:21]#[CH:22])[CH2:19][O:18][Si:1]([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1 | 0.75 | C1CCOC1 | c1ccncc1 | null | null | null | 96.8 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,348,892 | null | null | null | null | ord_dataset-6034127657614f02860ed057b62b882e | 2013-01-01T00:10:00 | true | In an analogous procedure to Example 651, part c, 7-Amino-5,5-dimethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-one and 3-(2,5-Dichloro-pyrimidin-4-ylamino)-N-methyl-benzamide were combined to yield 3-[5-Chloro-2-(5,5-dimethyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide (19.47 mg, 19% yield) as a white amorphous solid. 1H-NMR (CDCl3) δ 8.10 (s, 1H), 8.01 (s, 1H), 7.75 (d, J=7.8 Hz, 1H), 7.58 (d, J=8.60 Hz, 1H), 7.48 (m, 1H), 7.38 (m, 1H), 7.38 (m, 1H), 7.32 (s, 1H), 7.17 (d, J=14.9 Hz, 1H), 7.07 (s, 1H), 6.81 (d, J=7.8 Hz, 1H), 6.06 (br s, 1H), 2.97 (s, 3H), 2.37 (m, 2H), 2.07 (m, 2H), 1.33 (s, 6H). LC/MS (ESI+)=465 (M+H). MP=184.5° C. | CNC(=O)c1cccc(Nc2nc(Nc3ccc4c(c3)C(C)(C)CCC(=O)N4)ncc2Cl)c1 | null | CNC(=O)c1cccc(Nc2nc(Cl)ncc2Cl)c1 | CC1(C)CCC(=O)Nc2ccc(N)cc21 | null | [NH2:1][C:2]1[CH:15]=[CH:14][C:5]2[NH:6][C:7](=[O:13])[CH2:8][CH2:9][C:10]([CH3:12])([CH3:11])[C:4]=2[CH:3]=1.Cl[C:17]1[N:22]=[C:21]([NH:23][C:24]2[CH:25]=[C:26]([CH:31]=[CH:32][CH:33]=2)[C:27]([NH:29][CH3:30])=[O:28])[C:20]([Cl:34])=[CH:19][N:18]=1>>[Cl:34][C:20]1[C:21]([NH:23][C:24]2[CH:25]=[C:26]([CH:31]=[CH:32][CH:33]=2)[C:27]([NH:29][CH3:30])=[O:28])=[N:22][C:17]([NH:1][C:2]2[CH:15]=[CH:14][C:5]3[NH:6][C:7](=[O:13])[CH2:8][CH2:9][C:10]([CH3:12])([CH3:11])[C:4]=3[CH:3]=2)=[N:18][CH:19]=1 | null | null | null | null | null | 19 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
173,940 | [K+] | [OH-] | null | null | ord_dataset-3844acbccc714c04ab757ec4fca10bd0 | 1988-01-01T00:06:00 | true | To a stirred warm solution of 58.0 g (0.88 mol) of potassium hydroxide (85%) in 500 ml of methanol was added portionwise 81.7 g (0.21 mol) of 1,3,4,5-tetrahydro-3-(methoxycarbonyl)-4-(methoxyphenyl)-6-(trifluoromethyl)-2H-1-benzazepin-2-one - most of the solid dissolved. The mixture was diluted with 100 ml of dioxane and the resulting solution was refluxed for 6 hours. After standing overnight at room temperature, about 50% of the solvent was removed on a rotary evaporator and the residue was diluted with 4 liters of cold water. The insoluble material was filtered and dried (10 g) and the filtrate was cooled and treated portionwise with 270 ml of acetic acid to give a colorless granular solid. The latter was filtered, washed with cold water and dried in a desicator; yield 69.0 g, melting point 179°-181° C. (s. 128° C.). | COc1ccccc1C1Cc2c(cccc2C(F)(F)F)NC(=O)C1C(=O)O | null | COC(=O)C1C(=O)Nc2cccc(C(F)(F)F)c2CC1c1ccccc1OC | null | null | [OH-].[K+].C[O:4][C:5]([CH:7]1[CH:13]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[O:20][CH3:21])[CH2:12][C:11]2[C:22]([C:26]([F:29])([F:28])[F:27])=[CH:23][CH:24]=[CH:25][C:10]=2[NH:9][C:8]1=[O:30])=[O:6]>CO.O1CCOCC1>[C:5]([CH:7]1[CH:13]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[O:20][CH3:21])[CH2:12][C:11]2[C:22]([C:26]([F:28])([F:29])[F:27])=[CH:23][CH:24]=[CH:25][C:10]=2[NH:9][C:8]1=[O:30])([OH:6])=[O:4] | 8 | CO | C1COCCO1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
830,492 | null | null | null | null | ord_dataset-47bd90bf5ec74fcd99ce250a56e18c8f | 2008-01-01T00:07:00 | true | 4-{3-Hydroxy-1-[(methylamino)methyl]propyl}benzonitrile (0.55 g, 2.69 mmol) and DIPEA (0.77 g, 5.9 mmol) were dissolved in CH2Cl2 (5 mL). 3-Cyano-1-naphthoyl chloride (sse Method 11; 0.58 g, 2.69 mmol) was added in portions with stirring and cooling (external ice-bath). The mixture was stirred for 2 h with cooling and then diluted with CH2Cl2 (10 mL). The solution was washed twice with water, twice with a saturated aqueous KHSO4 solution and then with brine. The solvent was removed by evaporation and the residue flash chromatographed on silica gel (CH2Cl2-MeOH, 9:1). There was obtained 0.70 g (67%) of 3-cyano-N-[2-(4-cyanophenyl)-4-hydroxybutyl]-N-methyl-1-naphthamide as a white solid. 1H NMR (400 MHz, CDCl3): 1.4-2.5 (cm, 2H), 2.6 (s, 3H), 3.1-4.6 (cm, 6H), 6.4-7.8 (cm, 8H), 7.9 (d, 1H), 8.2 (s, 1H); LCMS: m/z 384 (M+1)+. | CN(CC(CCO)c1ccc(C#N)cc1)C(=O)c1cc(C#N)cc2ccccc12 | null | N#Cc1cc(C(=O)Cl)c2ccccc2c1 | CNCC(CCO)c1ccc(C#N)cc1 | null | [OH:1][CH2:2][CH2:3][CH:4]([C:8]1[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[CH:10][CH:9]=1)[CH2:5][NH:6][CH3:7].CCN(C(C)C)C(C)C.[C:25]([C:27]1[CH:28]=[C:29]([C:37](Cl)=[O:38])[C:30]2[C:35]([CH:36]=1)=[CH:34][CH:33]=[CH:32][CH:31]=2)#[N:26]>C(Cl)Cl>[C:25]([C:27]1[CH:28]=[C:29]([C:37]([N:6]([CH2:5][CH:4]([C:8]2[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[CH:10][CH:9]=2)[CH2:3][CH2:2][OH:1])[CH3:7])=[O:38])[C:30]2[C:35]([CH:36]=1)=[CH:34][CH:33]=[CH:32][CH:31]=2)#[N:26] | null | ClCCl | CCN(C(C)C)C(C)C | null | null | null | 67.9 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,703,575 | O=c1[nH]nc(CCc2ccccc2)cc1O | null | null | null | ord_dataset-54347fcace774f89850681d6dec8009f | 2016-01-01T00:03:00 | true | Prepared as described for 4-hydroxy-6-(2-phenylethyl)pyridazin-3(2H)-one (Example 1) from 3,4-bis(benzyloxy)-6-[(E)-2-[2,4-bis(trifluoromethyl)phenyl]-ethenyl]pyridazine (Intermediate 72) in 31% yield. | O=c1[nH]nc(CCc2ccc(C(F)(F)F)cc2C(F)(F)F)cc1O | null | FC(F)(F)c1ccc(/C=C/c2cc(OCc3ccccc3)c(OCc3ccccc3)nn2)c(C(F)(F)F)c1 | null | null | OC1C(=O)NN=C(CCC2C=CC=CC=2)C=1.C([O:24][C:25]1[N:26]=[N:27][C:28](/[CH:39]=[CH:40]/[C:41]2[CH:46]=[CH:45][C:44]([C:47]([F:50])([F:49])[F:48])=[CH:43][C:42]=2[C:51]([F:54])([F:53])[F:52])=[CH:29][C:30]=1[O:31]CC1C=CC=CC=1)C1C=CC=CC=1>>[F:54][C:51]([F:52])([F:53])[C:42]1[CH:43]=[C:44]([C:47]([F:48])([F:50])[F:49])[CH:45]=[CH:46][C:41]=1[CH2:40][CH2:39][C:28]1[CH:29]=[C:30]([OH:31])[C:25](=[O:24])[NH:26][N:27]=1 | null | null | null | null | null | null | 31 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
526,007 | null | null | null | null | ord_dataset-293186f5c9b441cab57f03cd3a18ac26 | 2001-01-01T00:11:00 | true | A mixture of 4-(2,3-diaminobenzoyl)amino-3-methoxy-N-methyl-N-[4-methyl-2-[5-(4-methylpiperazin-1-yl)carbonylpent-1-yloxy]phenyl]benzamide (150 mg) and diphenyl N-sulfamoylcarbonimidate (85 mg) in dichloromethane (8 ml) was refluxed for 24 hours under nitrogen. The reaction mixture was poured into water and extracted with chloroform. The organic layer was washed with water, driver over magnesium sulfate and evaporated in vacuo. The residue was purified by preparative thin-layer chromatography (chloroform:methanol=10:1/chloroform:methanol=6:1) to give 3-methoxy-N-methyl-N-[4-methyl-2-[5-(4-methylpiperazin-1-yl)carbonylpent-1-yloxy]phenyl]-4-(2-sulfamoylamino-1H-benzimidazol-4-yl)carbonylaminobenzamide (38 mg). | COc1cc(C(=O)N(C)c2ccc(C)cc2OCCCCCC(=O)N2CCN(C)CC2)ccc1NC(=O)c1cccc2[nH]c(NS(N)(=O)=O)nc12 | null | NS(=O)(=O)N=C(Oc1ccccc1)Oc1ccccc1 | COc1cc(C(=O)N(C)c2ccc(C)cc2OCCCCCC(=O)N2CCN(C)CC2)ccc1NC(=O)c1cccc(N)c1N | null | [NH2:1][C:2]1[C:44]([NH2:45])=[CH:43][CH:42]=[CH:41][C:3]=1[C:4]([NH:6][C:7]1[CH:38]=[CH:37][C:10]([C:11]([N:13]([CH3:36])[C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][C:15]=2[O:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][C:27]([N:29]2[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]2)=[O:28])=[O:12])=[CH:9][C:8]=1[O:39][CH3:40])=[O:5].[S:46]([N:50]=[C:51](OC1C=CC=CC=1)OC1C=CC=CC=1)(=[O:49])(=[O:48])[NH2:47].O>ClCCl>[CH3:40][O:39][C:8]1[CH:9]=[C:10]([CH:37]=[CH:38][C:7]=1[NH:6][C:4]([C:3]1[C:2]2[N:1]=[C:51]([NH:50][S:46](=[O:49])(=[O:48])[NH2:47])[NH:45][C:44]=2[CH:43]=[CH:42][CH:41]=1)=[O:5])[C:11]([N:13]([CH3:36])[C:14]1[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][C:15]=1[O:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][C:27]([N:29]1[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]1)=[O:28])=[O:12] | null | ClCCl | O | null | null | null | 21.7 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
882,795 | null | null | null | null | ord_dataset-3592bd645cd143ee8274cd0d834ae581 | 2009-01-01T00:05:00 | true | To a solution of Example 139 (40 mg, 0.078 mmol) in dioxane (3 mL) was added a solution of 6N aqueous hydrochloric acid (3 mL). The mixture was heated at 65 C for 3 hours, and the solvent removed in vacuo. The resultant residue was purified by reverse phase preparative HPLC on a Waters Symmetry C8 column (25 mm×100 mm, 7 μm particle size) using a gradient of 10% to 100% acetonitrile/0.1% trifluoroacetic acid in water over 8 minutes (10 minutes run time) at a flow rate of 40 mL/min to provide the title (4 mg, 9%). MS (ESI) m/z=550 (M−H)+. 1H NMR (300 MHz, DMSO-d6): δ 0.96 (m, 1H), 1.24 (m, 1H), 1.40 (s, 3H), 1.42 (s, 3H), 1.60 (s, 3H), 2.29 (m, 1H), 2.42 (m, 1H), 3.08 (s, 3H), 7.56 (m, 3H), 7.73 (m, 3H), 8.16 (d, J=7.4 Hz, 1H), 10.24 (s, 1H), 13.81 (s, 1H). | CC(C)(Cl)CCC1(C)C(=O)C(C2=NS(=O)(=O)c3cc(NS(C)(=O)=O)ccc3N2)=C(O)c2ccccc21 | null | CC(C)=CCC1(C)C(=O)C(C2=NS(=O)(=O)c3cc(NS(C)(=O)=O)ccc3N2)=C(O)c2ccccc21 | Cl | null | [OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([CH3:17])([CH2:12][CH:13]=[C:14]([CH3:16])[CH3:15])[C:4](=[O:18])[C:3]=1[C:19]1[NH:24][C:23]2[CH:25]=[CH:26][C:27]([NH:29][S:30]([CH3:33])(=[O:32])=[O:31])=[CH:28][C:22]=2[S:21](=[O:35])(=[O:34])[N:20]=1.[ClH:36]>O1CCOCC1>[Cl:36][C:14]([CH3:15])([CH3:16])[CH2:13][CH2:12][C:5]1([CH3:17])[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:2]([OH:1])=[C:3]([C:19]2[NH:24][C:23]3[CH:25]=[CH:26][C:27]([NH:29][S:30]([CH3:33])(=[O:32])=[O:31])=[CH:28][C:22]=3[S:21](=[O:35])(=[O:34])[N:20]=2)[C:4]1=[O:18] | null | C1COCCO1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
563,936 | [Pd] | null | null | null | ord_dataset-7c28974b7fcf4c9c86d5f2a42ba328a2 | 2002-01-01T00:09:00 | true | To a solution of ethyl 4-nitromesitylenate (7.7 g) in ethyl acetate (300 ml) was added 10% palladium-carbon (3 g) and the mixture was stirred for 3.5 hr under a hydrogen atmosphere. The catalyst was filtered off from the reaction mixture and the filtrate was washed with water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated to give the title compound (6.6 g) as pale-brown crystals. | CCOC(=O)c1cc(C)c(N)c(C)c1 | null | CCOC(=O)c1cc(C)c([N+](=O)[O-])c(C)c1 | null | null | [N+:1]([C:4]1[C:9]([CH3:10])=[CH:8][C:7]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:6][C:5]=1[CH3:16])([O-])=O>C(OCC)(=O)C.[C].[Pd]>[NH2:1][C:4]1[C:9]([CH3:10])=[CH:8][C:7]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:6][C:5]=1[CH3:16] | 3.5 | CCOC(C)=O | null | null | null | null | 99 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,283,230 | O=C([O-])O | [Na+] | null | null | ord_dataset-d5c54236ecd94d61aaa071461bcfc426 | 2013-01-01T00:04:00 | true | A solution of 1-[(1-methylcyclopropyl)sulfonyl]-3-[(triethylsilyl)oxy]azetidine (0.125 g, 0.41 mmol) in tetrahydrofuran (3 mL), water (1 mL) and acetic acid (1 mL) was stirred at room temperature for four hours. The mixture was neutralized by pouring into a solution of sodium bicarbonate. The product was extracted with ethyl acetate, the extracts were washed with brine, dried over sodium sulfate, decanted and concentrated to afford product, used without further purification (64 mg, 82%). | CC1(S(=O)(=O)N2CC(O)C2)CC1 | null | CC[Si](CC)(CC)OC1CN(S(=O)(=O)C2(C)CC2)C1 | null | null | [CH3:1][C:2]1([S:5]([N:8]2[CH2:11][CH:10]([O:12][Si](CC)(CC)CC)[CH2:9]2)(=[O:7])=[O:6])[CH2:4][CH2:3]1.C(=O)(O)[O-].[Na+]>O1CCCC1.O.C(O)(=O)C>[CH3:1][C:2]1([S:5]([N:8]2[CH2:9][CH:10]([OH:12])[CH2:11]2)(=[O:7])=[O:6])[CH2:4][CH2:3]1 | null | CC(=O)O | C1CCOC1 | 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 |
57,321 | Cl | [K+] | [OH-] | null | ord_dataset-56a7c92b497c48c59951f153285b4adc | 1979-01-01T00:07:00 | true | 2-Hydroxy-3,6-dichlorobenzoic acid (44.4 g) is dissolved in a solution of potassium hydroxide (11.2 g, 0.2 mole) and water (100 ml). The solution is heated to reflux (about 100° C.) and stirred vigorously while dimethyl sulfate (63.1 g, 0.5 mole) is added dropwise. The reaction mixture is then treated with a solution of potassium hydroxide (14.0 g, 0.25 mole) in 25.0 ml of water and refluxed for an additional 2 hours. The reaction mixture is then cooled and acidified to Congo red with hydrochloric acid to precipitate the desired 2-methoxy-3,6-dichlorobenzoic acid. | COc1c(Cl)ccc(Cl)c1C(=O)O | null | COS(=O)(=O)OC | O=C(O)c1c(Cl)ccc(Cl)c1O | null | [OH:1][C:2]1[C:10]([Cl:11])=[CH:9][CH:8]=[C:7]([Cl:12])[C:3]=1[C:4]([OH:6])=[O:5].[OH-].[K+].S(OC)(O[CH3:19])(=O)=O.Cl>O>[CH3:19][O:1][C:2]1[C:10]([Cl:11])=[CH:9][CH:8]=[C:7]([Cl:12])[C:3]=1[C:4]([OH:6])=[O:5] | null | O | null | null | 100 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,495,752 | [Cs+] | null | null | null | ord_dataset-366bdd9ee72d474cbe6f3f9e54dd96d2 | 2014-01-01T00:10:00 | true | 1-Bromopropane (192 mg, 1.57 mmol) was added to a solution of 2-chloro-5H-pyrrolo[3,2-d]pyrimidine (200 mg, 1.31 mmol) in DMF (15 mL) followed by cesium carbonate (0.855 g, 2.63 mmol), and the mixture was stirred at 70° C. for 0.5 h. Insoluble solids were filtered off, filtrate was concentrated and partitioned between ethyl acetate and water. Organic layer was separated, washed with brine, dried over sodium sulphate and filtered. The filtrate was concentrated in vacuo to afford title compound (0.22 g, 86%) as an oil. 1H NMR (300 MHz, CDCl3): δ 7.59 (d, J=8.7 Hz, 1H), 7.34 (d, J=3.3 Hz, 1H), 7.10 (d, J=8.4 Hz, 1H), 6.62 (d, J=3.6 Hz, 1H), 4.07 (t, J=6.9 Hz, 2H), 1.86 (m, 2H), 0.91 (t, J=7.5 Hz, 3H). | CCCn1ccc2nc(Cl)ccc21 | null | Clc1ncc2[nH]ccc2n1 | O=C([O-])[O-] | CCCBr | Br[CH2:2][CH2:3][CH3:4].[Cl:5][C:6]1N=[CH:8][C:9]2[NH:14][CH:13]=[CH:12][C:10]=2[N:11]=1.[C:15](=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[Cl:5][C:6]1[N:11]=[C:10]2[CH:12]=[CH:13][N:14]([CH2:2][CH2:3][CH3:4])[C:9]2=[CH:8][CH:15]=1 | 0.5 | CN(C)C=O | null | null | 70 | null | 86.3 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,549,652 | null | null | null | null | ord_dataset-cac8df8aff894288876df4e093c9877f | 2015-01-01T00:02:00 | true | 4.6 g of methyl 6-chloronicotinate and 40.5 ml of N-benzylethylenediamine are heated at 135° C. for 6 hours in a round-bottomed flask. The resulting product is poured into water and extraction is carried out with ethyl acetate. The resulting product is dried and evaporated under vacuum; the crude product thus obtained is purified by flash chromatography. | COC(=O)c1ccc(NCCNCc2ccccc2)nc1 | null | NCCNCc1ccccc1 | COC(=O)c1ccc(Cl)nc1 | null | Cl[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][N:3]=1.[CH2:12]([NH:19][CH2:20][CH2:21][NH2:22])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.O>C(OCC)(=O)C>[CH3:9][O:8][C:6](=[O:7])[C:5]1[CH:10]=[CH:11][C:2]([NH:22][CH2:21][CH2:20][NH:19][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[N:3][CH:4]=1 | null | CCOC(C)=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 |
1,649,591 | null | null | null | null | ord_dataset-bcc0b01d4f58457a8733b10a099f43ba | 2015-01-01T00:10:00 | true | To a solution of (S)-tert-butyl pyrrolidin-3-ylcarbamate (0.50 g, 2.7 mmol, 1 eq) and diisopropylamine (0.66 mL, 3.8 mmol, 1.4 eq) in 0.2 mL of NMP was added 4-chloropyrazolo[1,5-a]pyrazine (0.47 mL, 3.1 mmol, 1.1 eq). After stirring for 1 h at room temperature, the mixture was concentrated and purified by silica gel column chromatography (100% EtOAc) to afford (S)-tert-butyl (1-(pyrazolo[1,5-a]pyrazin-4-yl)pyrrolidin-3-yl)carbamate (0.740 g, 2.4 mmol, 91%). | CC(C)(C)OC(=O)N[C@H]1CCN(c2nccn3nccc23)C1 | null | CC(C)(C)OC(=O)N[C@H]1CCNC1 | Clc1nccn2nccc12 | null | [NH:1]1[CH2:5][CH2:4][C@H:3]([NH:6][C:7](=[O:13])[O:8][C:9]([CH3:12])([CH3:11])[CH3:10])[CH2:2]1.C(NC(C)C)(C)C.Cl[C:22]1[C:23]2[N:24]([N:28]=[CH:29][CH:30]=2)[CH:25]=[CH:26][N:27]=1>CN1C(=O)CCC1>[N:28]1[N:24]2[CH:25]=[CH:26][N:27]=[C:22]([N:1]3[CH2:5][CH2:4][C@H:3]([NH:6][C:7](=[O:13])[O:8][C:9]([CH3:10])([CH3:12])[CH3:11])[CH2:2]3)[C:23]2=[CH:30][CH:29]=1 | 1 | CC(C)NC(C)C | CN1CCCC1=O | null | 25 | null | 88.9 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,174,947 | [BH3-]C#N | [Na+] | null | null | ord_dataset-0f9d2dbe929a45c3892ae75e81e99443 | 2012-01-01T00:06:00 | true | A solution of 1-methyl-2-formylbenzimidazole (1 g) in methanol (27 mL) and acetic acid (0.54 mL) was treated with aminoacetaldehyde diethylacetal (0.9 g, 1 equivalent) and NaCNBH3 (0.85 g, 2 equivalents) at 25° C., stirred for 1 hour. The mixture was partitioned between water and ethyl acetate. The organic layer was separated, washed sequentially with saturated NaHCO3 and brine, and concentrated. The residue was chromatographed on silica gel, eluting with 8% methanol/dichloromethane to give 1.2 g (64%) of the title compound. | COC(CNCc1nc2ccccc2n1C)OC | null | Cn1c(C=O)nc2ccccc21 | CCOC(CN)OCC | null | [CH3:1][N:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[N:4]=[C:3]1[CH:11]=O.[CH2:13]([O:15][CH:16]([O:19][CH2:20]C)[CH2:17][NH2:18])C.[BH3-]C#N.[Na+]>CO.C(O)(=O)C>[CH3:13][O:15][CH:16]([O:19][CH3:20])[CH2:17][NH:18][CH2:11][C:3]1[N:2]([CH3:1])[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[N:4]=1 | 1 | CC(=O)O | CO | null | null | null | 77.1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
144,326 | null | null | null | null | ord_dataset-d6cdba90760a47779a36ece5962905eb | 1986-01-01T00:06:00 | true | 6-Amino-3,4-dihydrocarbostyril (1 g) is suspended in benzene (20 ml), and thereto is added dropwise a solution of N,N-dimethylcarbamoyl chloride (0.86 ml) in benzene (10 ml) at room temperature. The mixture is reacted at 50° C. for 3 hours, and thereto is added triethylamine (0.86 ml), and the mixture is further reacted at 50° to 60° C. for 5 hours. After the reaction, benzene is distilled off under reduced pressure, and water is added to the residue. The resulting precipitate is separated by filtration and washed with water. The crystal thus obtained is purified by silica gel column chromatography (solvent; chloroform:methanol=100:1) and then recrystallized from methanol-diethyl ether to give 6-(3,3-dimethylureido)-3,4-dihydrocarbostyril (0.6 g), as colorless prisms, m.p. 181°-183° C. | CN(C)C(=O)Nc1ccc2c(c1)CCC(=O)N2 | null | CN(C)C(=O)Cl | Nc1ccc2c(c1)CCC(=O)N2 | null | [NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH2:6][CH2:5]2.[CH3:13][N:14]([CH3:18])[C:15](Cl)=[O:16].C(N(CC)CC)C>C1C=CC=CC=1>[CH3:13][N:14]([CH3:18])[C:15](=[O:16])[NH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH2:6][CH2:5]2 | null | CCN(CC)CC | 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 |
1,045,453 | null | null | null | null | ord_dataset-dd320ded4b3f4764af39de99491533f7 | 2011-01-01T00:04:00 | true | The above mentioned tert-butyl (S)-1-(5-(3-fluoro-4-nitrophenyl)-1,3,4-thiadiazol-2-yl-boc-amino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate was dissolved in 20 mL 2M THF solution of methanamine (20 mL, 40 mmol) in a microwave heating tube. The tube was heated at 120° C. for 10 minutes. The THF solution was mixed with 200 mL EtOAc. The organic phase was washed with water, twice with saturated aqueous ammonium sulfate twice, and dried over sodium sulfate. After removing the solvent, the product was used directly in the next step. | CNc1cc(-c2nnc(N(C[C@H](Cc3ccc(C(F)(F)F)cc3)NC(=O)OC(C)(C)C)C(=O)OC(C)(C)C)s2)ccc1[N+](=O)[O-] | null | CN | CC(C)(C)OC(=O)N[C@@H](Cc1ccc(C(F)(F)F)cc1)CN(C(=O)OC(C)(C)C)c1nnc(-c2ccc([N+](=O)[O-])c(F)c2)s1 | null | F[C:2]1[CH:3]=[C:4]([C:11]2[S:15][C:14]([N:16]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:17][C@@H:18]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH2:19][C:20]3[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=3)=[N:13][N:12]=2)[CH:5]=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9].[CH3:45][NH2:46].CCOC(C)=O>C1COCC1>[CH3:45][NH:46][C:2]1[CH:3]=[C:4]([C:11]2[S:15][C:14]([N:16]([C:38]([O:40][C:41]([CH3:44])([CH3:42])[CH3:43])=[O:39])[CH2:17][C@@H:18]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:34])[CH3:35])[CH2:19][C:20]3[CH:21]=[CH:22][C:23]([C:26]([F:29])([F:27])[F:28])=[CH:24][CH:25]=3)=[N:13][N:12]=2)[CH:5]=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9] | null | CCOC(C)=O | C1CCOC1 | null | 120 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
880,434 | O=C(C(F)(F)F)C(F)(F)F | [F-] | [K+] | null | ord_dataset-3592bd645cd143ee8274cd0d834ae581 | 2009-01-01T00:05:00 | true | CH2═C(CF3)CF2OSO2F (10 g, 0.041 mole) is added at 20° C. to (CF3)2CFOK, prepared from freshly dried potassium fluoride (KF) (2.4 g, 0.041 mole), hexafluoroacetone (HFA) (9.3 g, 0.056 mole) and dry diglyme (10 ml). The reaction mixture is agitated for 2 hours and then poured into water, the organic layer separating. The organic layer is washed with dilute hydrochloric acid, then sodium bicarbonate solution, then water, after which it is dried over magnesium sulfate (MgSO4). Distillation of the reaction mixture gives CH2═C(CF3)CF2OCF(CF3)2 (10.2 g, 75% yield, b.pt. 87-88° C.). | C=C(C(F)(F)F)C(F)(F)OC(F)(C(F)(F)F)C(F)(F)F | null | C=C(C(F)(F)F)C(F)(F)OS(=O)(=O)F | FC(F)(F)C(F)(O[K])C(F)(F)F | null | [CH2:1]=[C:2]([C:7]([O:10]S(F)(=O)=O)([F:9])[F:8])[C:3]([F:6])([F:5])[F:4].[C:15](O[K])([C:21]([F:24])([F:23])[F:22])([C:17]([F:20])([F:19])[F:18])[F:16].[F-].[K+].FC(F)(F)C(C(F)(F)F)=O>O.COCCOCCOC>[CH2:1]=[C:2]([C:7]([O:10][C:15]([C:21]([F:24])([F:23])[F:22])([C:17]([F:20])([F:19])[F:18])[F:16])([F:9])[F:8])[C:3]([F:6])([F:5])[F:4] | 2 | O | COCCOCCOC | null | null | 75 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,070,361 | Cl | null | null | null | ord_dataset-5df93261afc143c3ae919a57ff4fc1d4 | 2011-01-01T00:07:00 | true | To a suspension of trans-2-aminocyclohexylmethanol hydrochloride (214 mg, 1.30 mmol) and triethylamine (0.538 mL, 3.9 mmol) in 5 mL dichloromethane at 0° C. was added a solution of 5-chlorothiophene-2-sulfonyl chloride (0.267 mL, 1.23 mmol) in 1 mL dichloromethane. The reaction was stirred at 0° C. for 30 min and at room temperature for 30 min. The crude reaction mixture was purified by flash chromatography on silica gel using a gradient of 0 to 100% ethyl acetate in hexane to give 5-chloro-N-(trans-2-(hydroxymethyl)cyclohexyl)thiophene-2-sulfonamide (330 mg, 84%). 1H NMR (400 MHz, CDCl3) δ ppm 7.40 (d, J=4.03 Hz, 1H), 6.91 (d, J=4.03 Hz, 1H), 5.24 (d, J=7.30 Hz, 1H), 3.86 (d, J=11.33 Hz, 1H), 3.32-3.48 (m, 1H), 3.05 (d, J=6.55 Hz, 1H), 2.32 (br. s., 1H), 1.72-1.83 (m, 1H), 1.58-1.73 (m, 3H), 1.11-1.36 (m, 5H). MS [M+H]+=310; [M+Na]+=332. | O=S(=O)(N[C@@H]1CCCC[C@H]1CO)c1ccc(Cl)s1 | null | N[C@@H]1CCCC[C@H]1CO | O=S(=O)(Cl)c1ccc(Cl)s1 | null | Cl.[NH2:2][C@@H:3]1[CH2:8][CH2:7][CH2:6][CH2:5][C@H:4]1[CH2:9][OH:10].C(N(CC)CC)C.[Cl:18][C:19]1[S:23][C:22]([S:24](Cl)(=[O:26])=[O:25])=[CH:21][CH:20]=1>ClCCl>[Cl:18][C:19]1[S:23][C:22]([S:24]([NH:2][C@@H:3]2[CH2:8][CH2:7][CH2:6][CH2:5][C@H:4]2[CH2:9][OH:10])(=[O:26])=[O:25])=[CH:21][CH:20]=1 | 0.5 | CCN(CC)CC | ClCCl | null | 0 | null | 86.6 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
318,313 | [H-] | [Na+] | null | null | ord_dataset-eb32c2b9cbdf4fc39ce6c9fe0fa11430 | 1995-01-01T00:10:00 | true | To a solution of 3-(pyridin-3-yl)-7-(6-phenylmethoxyindol-3-yl)carbonyl-1H,3H-pyrrolo[1,2-c]thiazole (200 mg, 0.443 mmol), prepared as in Example 4, in DMF (12 mL) was added NaH (60% oil dispersion, 19 mg, 0.465 mmol) and the reaction mixture was stirred for 7 min at ambient temperature. 4-nitrophenyl chloroformate (94 mg, 0.45 mmol) was added and the amber solution was stirred for two hours at ambient temperature. The reaction mixture was partitioned between H2O and ethyl acetate. The organic phase was dried over MgSO4, filtered,and concentrated. The title compound (98 mg), was purified by flash chromatography on silica gel (60 g, 1:1 ethyl acetate, hexanes). | O=C(c1ccn2c1CSC2c1cccnc1)c1cn(C(=O)Oc2ccc([N+](=O)[O-])cc2)c2cc(OCc3ccccc3)ccc12 | null | O=C(c1ccn2c1CSC2c1cccnc1)c1c[nH]c2cc(OCc3ccccc3)ccc12 | O=C(Cl)Oc1ccc([N+](=O)[O-])cc1 | null | [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH:7]2[N:11]3[CH:12]=[CH:13][C:14]([C:15]([C:17]4[C:25]5[C:20](=[CH:21][C:22]([O:26][CH2:27][C:28]6[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=6)=[CH:23][CH:24]=5)[NH:19][CH:18]=4)=[O:16])=[C:10]3[CH2:9][S:8]2)[CH:2]=1.[H-].[Na+].Cl[C:37]([O:39][C:40]1[CH:45]=[CH:44][C:43]([N+:46]([O-:48])=[O:47])=[CH:42][CH:41]=1)=[O:38]>CN(C=O)C>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH:7]2[N:11]3[CH:12]=[CH:13][C:14]([C:15]([C:17]4[C:25]5[C:20](=[CH:21][C:22]([O:26][CH2:27][C:28]6[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=6)=[CH:23][CH:24]=5)[N:19]([C:37]([O:39][C:40]5[CH:41]=[CH:42][C:43]([N+:46]([O-:48])=[O:47])=[CH:44][CH:45]=5)=[O:38])[CH:18]=4)=[O:16])=[C:10]3[CH2:9][S:8]2)[CH:2]=1 | 0.12 | CN(C)C=O | null | null | 25 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,607,743 | null | null | null | null | ord_dataset-9cecb3a8d3b9494191b28dcefea66af2 | 2015-01-01T00:07:00 | true | To a solution of the compound (0.10 g) obtained in Example 33, step 1 in THF (3 mL)/diethyl ether (3 mL) was added tert-butyl isocyanate (41 μL), and the mixture was stirred at room temperature for 16 hr. The solvent was evaporated under reduced pressure, and the obtained solid was washed with diethyl ether/hexane to give tert-butyl 8-{4-[(tert-butylamino)carbonyl]piperazin-1-yl}-2,3-dihydropyrido[3,2-f][1,4]oxazepine-4(5H)-carboxylate (0.11 g, 85%) as a white powder. | CC(C)(C)NC(=O)N1CCN(c2ccc3c(n2)OCCN(C(=O)OC(C)(C)C)C3)CC1 | null | CC(C)(C)N=C=O | CC(C)(C)OC(=O)N1CCOc2nc(N3CCNCC3)ccc2C1 | null | [N:1]1([C:7]2[CH:8]=[CH:9][C:10]3[CH2:11][N:12]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13][CH2:14][O:15][C:16]=3[N:17]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.C(OCC)C.[C:30]([N:34]=[C:35]=[O:36])([CH3:33])([CH3:32])[CH3:31]>C1COCC1>[C:30]([NH:34][C:35]([N:4]1[CH2:5][CH2:6][N:1]([C:7]2[CH:8]=[CH:9][C:10]3[CH2:11][N:12]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13][CH2:14][O:15][C:16]=3[N:17]=2)[CH2:2][CH2:3]1)=[O:36])([CH3:33])([CH3:32])[CH3:31] | 16 | C1CCOC1 | CCOCC | null | 25 | null | 85 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,035,997 | null | null | null | null | ord_dataset-3af92aec23dc4810b92eb0d8c60023ee | 2011-01-01T00:03:00 | true | Isobutylamine (15.6 mL, 157 mmol) was added dropwise to a 5° C. solution of 4-chloro-3-nitro[1,5]naphthyridine (15.0 g, 71.6 mmol) in dichloromethane (300 mL). The reaction was allowed to stir at room temperature for 4 hours, then was concentrated under reduced pressure to afford a residue that was treated with water (300 mL). The mixture was stirred for 30 minutes, then a solid was isolated by filtration, rinsed with water (100 mL), and dried in a vacuum oven at 50° C. overnight to afford 17.25 g of N-(2-methylpropyl)-3-nitro[1,5]naphthyridin-4-amine as a yellow solid. | CC(C)CNc1c([N+](=O)[O-])cnc2cccnc12 | null | O=[N+]([O-])c1cnc2cccnc2c1Cl | CC(C)CN | null | [CH2:1]([NH2:5])[CH:2]([CH3:4])[CH3:3].Cl[C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][N:15]=2)[N:10]=[CH:9][C:8]=1[N+:17]([O-:19])=[O:18].O>ClCCl>[CH3:3][CH:2]([CH3:4])[CH2:1][NH:5][C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][N:15]=2)[N:10]=[CH:9][C:8]=1[N+:17]([O-:19])=[O:18] | 4 | O | ClCCl | null | 25 | 97.8 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,437,344 | C=C[Mg]Br | null | null | null | ord_dataset-275a3da8f45f4536ad29727f0ef9ba66 | 2014-01-01T00:06:00 | true | In a flame dried roundbottomflask (E)-but-2-enoic acid methoxy-methyl-amide (Einhorn et al., Synth. Commun. 20 (8), 1105-1112 (1990)) (8.0 g, 61.9 mmol) was dissolved in 150 ml of THF. A 1M solution of vinylmagnesium bromide in Et2O (68.1 ml, 68.1 mmol) was added at 0° C. and then the mixture was stirred for 1 h at rt. (S)-(−)-alpha-methylbenzylamin (15.8 ml, 124 mmol) was added at rt, followed by water (15 ml). The reaction was stirred at rt for 1 h. THF was evaporated and 150 ml of water was added. Then the mixture was extracted three times with CH2Cl2 The organic layer was washed with brine, dried over Na2 SO4 and evaporated. The crude product was purified by flash chromatography (silica gel, 20% EtOAc/cyclohexane) which furnished the (S,S) product as the first fraction (confirmed by x-ray). | C[C@H]1CC(=O)CCN1[C@@H](C)c1ccccc1 | null | CCc1nn2c(C)cc(C)nc2c1Cc1ccc(O)cc1 | C[C@H](N)c1ccccc1 | null | C(C1C(C[C:15]2[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=2)=C2N=C(C)C=C(C)N2N=1)C.C([Mg]Br)=C.CCOCC.[CH3:31][C@H:32]([NH2:39])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>C1COCC1.O>[CH3:15][C@H:16]1[CH2:17][C:18](=[O:21])[CH2:19][CH2:20][N:39]1[C@H:32]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[CH3:31] | 1 | O | C1CCOC1 | CCOCC | 25 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,707,554 | [Na] | null | null | null | ord_dataset-54347fcace774f89850681d6dec8009f | 2016-01-01T00:03:00 | true | Sodium metal (12 mg, 0.52 mmol) was added to anhydrous ethanol (3 mL) at room temperature and the mixture was stirred for 15 min. 1-(1H-pyrazol-1-yl)cyclopropanecarbonitrile (0.1 g, 0.75 mmol) dissolved in ethanol (2 mL) was added and the reaction mixture was heated to 70° C. for 90 min. The resulting solution was used without further purification. | CCOC(=N)C1(n2cccn2)CC1 | null | N#CC1(n2cccn2)CC1 | CCO | null | [Na].[N:2]1([C:7]2([C:10]#[N:11])[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[N:3]1.[CH2:12]([OH:14])[CH3:13]>>[N:2]1([C:7]2([C:10](=[NH:11])[O:14][CH2:12][CH3:13])[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[N:3]1 | 0.25 | null | null | null | 70 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
848,765 | [BH4-] | [Na+] | null | null | ord_dataset-171b840ae6e84e45bab43b987d09f5c7 | 2008-01-01T00:11:00 | true | To a solution of 2-(tetrahydropyran-4-ylamino)-6-(2-fluorobenzoyl)thieno[2,3-d]pyrimidine (300 mg) in ethanol (30 mL) was added sodium borohydride (0.4 g) at room temperature and stirred overnight. Ethyl acetate (50 mL) was added to the reaction mixture. The organic layer was separated, washed with brine, dried, and evaporated. Purification by preparative TLC (silica gel, 50% EtOAc/hexanes) gave 140 mg of the alcohol. MS: 360.2 (M+H). | OC(c1cc2cnc(NC3CCOCC3)nc2s1)c1ccccc1F | null | O=C(c1cc2cnc(NC3CCOCC3)nc2s1)c1ccccc1F | null | null | [O:1]1[CH2:6][CH2:5][CH:4]([NH:7][C:8]2[N:9]=[CH:10][C:11]3[CH:16]=[C:15]([C:17](=[O:25])[C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=4[F:24])[S:14][C:12]=3[N:13]=2)[CH2:3][CH2:2]1.[BH4-].[Na+].C(OCC)(=O)C>C(O)C>[O:1]1[CH2:2][CH2:3][CH:4]([NH:7][C:8]2[N:9]=[CH:10][C:11]3[CH:16]=[C:15]([CH:17]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=4[F:24])[OH:25])[S:14][C:12]=3[N:13]=2)[CH2:5][CH2:6]1 | 8 | CCO | CCOC(C)=O | null | null | 46.4 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
26,446 | O=C([O-])[O-] | [Na+] | null | null | ord_dataset-2ada3fda46fc44719ba0c8001f53c1b3 | 1977-01-01T00:06:00 | true | A mixture of 7.3 parts of N-(2-bromoethyl)-4-fluoro-2-nitrobenzamide, 6.2 parts of 5-chloro-1,3-dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-one, 5.2 parts of sodium carbonate and 80 parts of 4-methyl-2-pentanone is stirred and refluxed overnight. The reaction mixture is cooled, water is added and the layers are separated. The aqueous phase is extracted with 4-methyl-2-pentanone. The combined organic phases are washed with water, dried, filtered and evaporated. The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (90:10 by volume) as eluent. The pure fractions are collected and the eluent is evaporated. The oily residue is crystallized from 2-propanone. The product is filtered off and dried, yielding 1 part of N-{2-[4-(5-chloro-2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)-1-piperidinyl]-ethyl}-4-fluoro-2-nitrobenzamide. | O=C(NCCN1CCC(n2c(=O)[nH]c3cc(Cl)ccc32)CC1)c1ccc(F)cc1[N+](=O)[O-] | null | O=c1[nH]c2cc(Cl)ccc2n1C1CCNCC1 | O=C(NCCBr)c1ccc(F)cc1[N+](=O)[O-] | null | Br[CH2:2][CH2:3][NH:4][C:5](=[O:16])[C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][C:7]=1[N+:13]([O-:15])=[O:14].[Cl:17][C:18]1[CH:33]=[CH:32][C:21]2[N:22]([CH:26]3[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]3)[C:23](=[O:25])[NH:24][C:20]=2[CH:19]=1.C(=O)([O-])[O-].[Na+].[Na+].CC(C)CC(=O)C>O>[Cl:17][C:18]1[CH:33]=[CH:32][C:21]2[N:22]([CH:26]3[CH2:27][CH2:28][N:29]([CH2:2][CH2:3][NH:4][C:5](=[O:16])[C:6]4[CH:11]=[CH:10][C:9]([F:12])=[CH:8][C:7]=4[N+:13]([O-:15])=[O:14])[CH2:30][CH2:31]3)[C:23](=[O:25])[NH:24][C:20]=2[CH:19]=1 | null | O | CC(=O)CC(C)C | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
11,646 | null | null | null | null | ord_dataset-7c810806c4564bada4a9550135bbb06f | 1976-01-01T00:08:00 | true | The reaction of ethyl 2-hydroxyimino-2-cyanoacetate (8.5 g) with ethyl chloroformate (6.0 g) is carried out as in Example 3 to give ethyl 2-ethoxycarbonyloxyimino-2-cyanoacetate (8.8 g) as an oil. | CCOC(=O)ON=C(C#N)C(=O)OCC | null | CCOC(=O)C(C#N)=NO | CCOC(=O)Cl | null | [OH:1][N:2]=[C:3]([C:9]#[N:10])[C:4]([O:6][CH2:7][CH3:8])=[O:5].Cl[C:12]([O:14][CH2:15][CH3:16])=[O:13]>>[CH2:15]([O:14][C:12]([O:1][N:2]=[C:3]([C:9]#[N:10])[C:4]([O:6][CH2:7][CH3:8])=[O:5])=[O:13])[CH3:16] | null | null | null | null | null | null | 74.3 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
516,276 | BrB(Br)Br | null | null | null | ord_dataset-a495451286334c5c9bbcbd48a00c1350 | 2001-01-01T00:09:00 | true | To a solution of {2-[3-ethyl-3-(3-methoxy-phenyl)-2-oxo-azepan-1-yl]-ethyl}-urea (as described above in Step B) (0.14 g, 0.421 mmol) in CH2Cl2 (10 mL) at −78° C. was added BBr3 (1M, 0.842 mL, 0.842 rnmol). After stirring for 1 hr at 25° C. the reaction was quenched with H2O and partitioned with EtOAc and 10% HCl. The organic layer was washed with brine and dried (MgSO4), and the solvent removed in vacuo to obtain the title compound. | CCC1(c2cccc(O)c2)CCCCN(CCNC(N)=O)C1=O | null | CCC1(c2cccc(OC)c2)CCCCN(CCNC(N)=O)C1=O | null | null | [CH2:1]([C:3]1([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([O:23]C)[CH:18]=2)[CH2:9][CH2:8][CH2:7][CH2:6][N:5]([CH2:10][CH2:11][NH:12][C:13]([NH2:15])=[O:14])[C:4]1=[O:16])[CH3:2].B(Br)(Br)Br>C(Cl)Cl>[CH2:1]([C:3]1([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([OH:23])[CH:18]=2)[CH2:9][CH2:8][CH2:7][CH2:6][N:5]([CH2:10][CH2:11][NH:12][C:13]([NH2:15])=[O:14])[C:4]1=[O:16])[CH3:2] | 1 | ClCCl | null | null | 25 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
853,503 | [K+] | null | null | null | ord_dataset-faa0236be76c4501841c954527cd1b6c | 2008-01-01T00:12:00 | true | A mixture of 2-bromopyridine (3.4 mmol), 3-pyrazolecarboxaldehyde (3.2 mmol), and potassium carbonate (3.4 mmol) in anhydrous DMF (6 mL) was heated to 120° C. for 24 h. The reaction was cooled to RT, diluted with water, and extracted with EtOAc (3 x). The organic layers were combined and dried (Na2SO4), filtered, and concentrated. The title compound was obtained upon purification (SGC using EtOAc:hexanes gradient eluant from 0% to 100% EtOAc). | O=Cc1cnn(-c2ccccn2)c1 | null | O=C([O-])[O-] | O=Cc1cc[nH]n1 | Brc1ccccn1 | Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[NH:8]1[CH:12]=[CH:11][C:10](C=O)=[N:9]1.[C:15](=O)([O-])[O-:16].[K+].[K+]>CN(C=O)C.O>[N:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[N:9]1[CH:10]=[C:11]([CH:15]=[O:16])[CH:12]=[N:8]1 | null | O | CN(C)C=O | null | 120 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,395,874 | [Pd] | CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21 | O=C(/C=C/c1ccccc1)/C=C/c1ccccc1 | null | ord_dataset-12dc3bd21bcf44d09e5b4249afe15161 | 2014-01-01T00:02:00 | true | A mixture of 2-(5-bromo-2-neopentyl-1H-benzo[d]imidazol-1-yl)-N,N-dimethylethanamine (prepared in STEP A of Example 1, 1.41 g, 4.15 mmol), tert-butyl 4-(mercaptomethyl)piperidine-1-carboxylate (prepared in STEP B of Example 5, 1.20 g, 5.19 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (120 mg, 0.208 mmol), tris(dibenzylideneacetone)dipalladium(0) (95.2 mg, 0.104 mmol) and N,N-diisopropylethylamine (1.09 mL, 6.23 mmol) in 1,4-dioxane (8.5 mL) was stirred at 130° C. for 18 h. The mixture was filtered through a celite and the filtrate was concentrated in vacuo. The residue (2.40 g) was used for the next step without purification. | CN(C)CCn1c(CC(C)(C)C)nc2cc(SCC3CCN(C(=O)OC(C)(C)C)CC3)ccc21 | null | CN(C)CCn1c(CC(C)(C)C)nc2cc(Br)ccc21 | CC(C)(C)OC(=O)N1CCC(CS)CC1 | null | Br[C:2]1[CH:20]=[CH:19][C:5]2[N:6]([CH2:14][CH2:15][N:16]([CH3:18])[CH3:17])[C:7]([CH2:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[N:8][C:4]=2[CH:3]=1.[SH:21][CH2:22][CH:23]1[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(N(CC)C(C)C)(C)C>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:17][N:16]([CH3:18])[CH2:15][CH2:14][N:6]1[C:5]2[CH:19]=[CH:20][C:2]([S:21][CH2:22][CH:23]3[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]3)=[CH:3][C:4]=2[N:8]=[C:7]1[CH2:9][C:10]([CH3:13])([CH3:12])[CH3:11] | 18 | CCN(C(C)C)C(C)C | C1COCCO1 | null | 130 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
966,514 | [Li+] | [OH-] | null | null | ord_dataset-03ba810b7f464a06b5d8787af2e8b64e | 2010-01-01T00:06:00 | true | Methyl 3-[(dipropylamino)carbonyl]-5-(1,3-thiazol-2-yl)benzoate (4.4 g, 12.8 mmol) is dissolved in 1:1:1 tetrahydrofuran/methanol/water (60 mL), and lithium hydroxide monohydrate is added (1.1 g, 25.6 mmol). The reaction is stirred 15 min and is concentrated under reduced pressure. The residue is diluted in chloroform and washed with water, brine, dried (magnesium sulfate), filtered, and concentrated under reduced pressure to give the title compound. ESI MS m/z 333.1 [M+H]+. | CCCN(CCC)C(=O)c1cc(C(=O)O)cc(-c2nccs2)c1 | null | CCCN(CCC)C(=O)c1cc(C(=O)OC)cc(-c2nccs2)c1 | null | null | [CH2:1]([N:4]([CH2:22][CH2:23][CH3:24])[C:5]([C:7]1[CH:8]=[C:9]([CH:14]=[C:15]([C:17]2[S:18][CH:19]=[CH:20][N:21]=2)[CH:16]=1)[C:10]([O:12]C)=[O:11])=[O:6])[CH2:2][CH3:3]>O1CCCC1.CO.O.O.[OH-].[Li+]>[CH2:22]([N:4]([CH2:1][CH2:2][CH3:3])[C:5]([C:7]1[CH:8]=[C:9]([CH:14]=[C:15]([C:17]2[S:18][CH:19]=[CH:20][N:21]=2)[CH:16]=1)[C:10]([OH:12])=[O:11])=[O:6])[CH2:23][CH3:24] | 0.25 | CO | C1CCOC1 | 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 |
516,053 | CN(C)C(On1nnc2ccccc21)=[N+](C)C | Cl | F[B-](F)(F)F | null | ord_dataset-a495451286334c5c9bbcbd48a00c1350 | 2001-01-01T00:09:00 | true | To a solution of 3-amino-1-(4-methoxybenzyl)-4-methyl-2-pyridone (5.03 g, 20.6 mmol), DIEA (3.76 mL, 21.6 mmol) and N-Boc-p-nitrophenylalanine (6.71 g, 21.6 mmol) in acetonitrile (100 mL) cooled on ice was added TBTU (7.94 g, 24.7 mmol). The mixture was stirred at rt overnight. Additional DIEA (3.76 mL, 21,6 mmol) was added, and the slurry was stirred for another 6 hours. 1N HCl (50 mL) was added, and the acetonitrile was removed under reduced pressure. Ethyl acetate (300 mL) was added, and the organic suspension was separated and washed with 1N HCl, 2.5N NaOH and brine. Ethyl acetate (50 mL) and THF (100 mL) were added to the suspension to dissolve all solids, and the organic phase was washed with brine, and dried (MgSO4/silica gel/charcoal). Evaporation of the solvent gave 3-2′-(S)-tbutoxycarbonylamino-3′-(4″-nitro)benzene]propanoylamino-1-(4-methoxybenzyl)-4-methyl-2-pyridone as a brown solid (9.73 g, 88%). | CCC(=O)Nc1c(C)ccn(Cc2ccc(OC)cc2)c1=O | null | COc1ccc(Cn2ccc(C)c(N)c2=O)cc1 | CC(C)(C)OC(=O)N[C@@H](Cc1ccc([N+](=O)[O-])cc1)C(=O)O | null | [NH2:1][C:2]1[C:3](=[O:18])[N:4]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=2)[CH:5]=[CH:6][C:7]=1[CH3:8].CCN(C(C)C)C(C)C.C(N[C@H:36]([C:47](O)=[O:48])[CH2:37]C1C=CC([N+]([O-])=O)=CC=1)(OC(C)(C)C)=O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.Cl>C(#N)C>[C:47]([NH:1][C:2]1[C:3](=[O:18])[N:4]([CH2:9][C:10]2[CH:11]=[CH:12][C:13]([O:16][CH3:17])=[CH:14][CH:15]=2)[CH:5]=[CH:6][C:7]=1[CH3:8])(=[O:48])[CH2:36][CH3:37] | 8 | CC#N | CCN(C(C)C)C(C)C | null | 25 | 157.3 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,184,177 | Cc1ccc(S(=O)(=O)O)cc1 | null | null | null | ord_dataset-9cd817a75dfc4fe7ad19d4232772d5ff | 2012-01-01T00:07:00 | true | To a solution of 4-bromo-benzene-1,2-diamine (3.0 g, 16.1 mmol) in anhydrous toluene (50 ml) was added a solution of 3-cyclohexyl-acryloyl chloride (as prepared in STEP B above, 32.5 mmol) in toluene (5 ml). The resulting solution was stirred at 40° C. for 6 h. To the resulting solution was added p-toluenesulfonic acid (3.0 g, 16 mmol) and heated to reflux for 18 h. The resulting solution was concentrated. The residue obtained was partitioned between ethyl acetate and a saturated solution of sodium bicarbonate. The layers were separated. The organic layer was washed successively with saturated sodium bicarbonate, water, brine, then dried over sodium sulfate, filtered and concentrated. The residue was chromatographed using a silica gel to yield 5-bromo-2-(2-cyclohexyl-vinyl)-1H-benzoimidazole. | Brc1ccc2[nH]c(C=CC3CCCCC3)nc2c1 | null | Nc1ccc(Br)cc1N | O=C(Cl)C=CC1CCCCC1 | null | [Br:1][C:2]1[CH:3]=[C:4]([NH2:9])[C:5]([NH2:8])=[CH:6][CH:7]=1.[CH:10]1([CH:16]=[CH:17][C:18](Cl)=O)[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]2[NH:8][C:18]([CH:17]=[CH:16][CH:10]3[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]3)=[N:9][C:4]=2[CH:3]=1 | 6 | Cc1ccccc1 | null | null | 40 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
530,906 | [BH4-] | [Na+] | null | null | ord_dataset-7774db17e619477ea20ee621abe71257 | 2002-01-01T00:01:00 | true | 7-Chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-{4-[2-(2-methylphenyl)acetyl]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine (2.06 g) is dissolved in a mixture of methylene chloride (20 ml) and methanol (20 ml), and thereto ia added with stirring sodium borohydride (0.28 g) under cooling over an ice-bath. The mixture is stirred for two hours over an ice-bath, and the mixture is evaporated to remove almost of the solvent. To the residue is added water, and the mixture is extracted with methylene chloride. The organic layer is washed with a saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated. The residue is purified by silica gel column chromatography (solvent; methylene chloride:methanol=20˜10:1) to give 7-chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-{4-[2-(2-methylphenyl)-1-hydroxyethyl]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine (2.08 g) as colorless amorphous. | Cc1ccccc1CC(O)c1ccc(C(=O)N2CCCC(CC(=O)N3CCN(C)CC3)c3cc(Cl)ccc32)cc1 | null | Cc1ccccc1CC(=O)c1ccc(C(=O)N2CCCC(CC(=O)N3CCN(C)CC3)c3cc(Cl)ccc32)cc1 | null | null | [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([C:12](=[O:29])[C:13]3[CH:18]=[CH:17][C:16]([C:19](=[O:28])[CH2:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[CH3:27])=[CH:15][CH:14]=3)[CH2:10][CH2:9][CH2:8][CH:7]([CH2:30][C:31]([N:33]3[CH2:38][CH2:37][N:36]([CH3:39])[CH2:35][CH2:34]3)=[O:32])[C:6]=2[CH:40]=1.[BH4-].[Na+]>C(Cl)Cl.CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([C:12](=[O:29])[C:13]3[CH:18]=[CH:17][C:16]([CH:19]([OH:28])[CH2:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[CH3:27])=[CH:15][CH:14]=3)[CH2:10][CH2:9][CH2:8][CH:7]([CH2:30][C:31]([N:33]3[CH2:38][CH2:37][N:36]([CH3:39])[CH2:35][CH2:34]3)=[O:32])[C:6]=2[CH:40]=1 | 2 | CO | ClCCl | null | null | 100.6 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,541,479 | null | null | null | null | ord_dataset-cac8df8aff894288876df4e093c9877f | 2015-01-01T00:02:00 | true | The crude product N-hydroxy-1-[2-(trimethylsilyl)ethoxy]methyl-1H-pyrrolo[2,3-b]pyridine-4-carboximidamide (0.06 gm, 0.0002 mol) was dissolved in pyridine (1.0 mL, 0.012 mol) and then 3-cyanobenzoyl chloride (0.040 g, 0.00024 mol) was added at rt. This mixture was stirred for 1 h and heated to 80° C. in an oil bath. After heating for 18 h the reaction was allowed to cool to rt and then diluted with ACN and concentrated in vacuo to give 3-[3-(1-[2-(trimethylsilyl)ethoxy]methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-1,2,4-oxadiazol-5-yl]benzonitrile 0.08 gm as an off white residue, LC/MS (M+H)+ 418. | C[Si](C)(C)CCOCn1ccc2c(-c3noc(-c4cccc(C#N)c4)n3)ccnc21 | null | N#Cc1cccc(C(=O)Cl)c1 | C[Si](C)(C)CCOCn1ccc2c(C(=N)NO)ccnc21 | null | [OH:1][NH:2][C:3]([C:5]1[C:6]2[CH:13]=[CH:12][N:11]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[C:7]=2[N:8]=[CH:9][CH:10]=1)=[NH:4].N1C=CC=CC=1.[C:28]([C:30]1[CH:31]=[C:32]([CH:36]=[CH:37][CH:38]=1)[C:33](Cl)=O)#[N:29]>C(#N)C>[CH3:19][Si:18]([CH3:21])([CH3:20])[CH2:17][CH2:16][O:15][CH2:14][N:11]1[C:7]2=[N:8][CH:9]=[CH:10][C:5]([C:3]3[N:4]=[C:33]([C:32]4[CH:31]=[C:30]([CH:38]=[CH:37][CH:36]=4)[C:28]#[N:29])[O:1][N:2]=3)=[C:6]2[CH:13]=[CH:12]1 | 1 | c1ccncc1 | CC#N | null | 80 | null | 95.8 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
843,364 | null | null | null | null | ord_dataset-e2b35e721c2741999b0005d12691f9fe | 2008-01-01T00:10:00 | true | The pyrazole acid, prepared as described in Procedure 8, was coupled with (R)—N,N-dimethyl-4-phenyl-1,2-butanediamine (prepared as shown in Procedure 2) using the method of Procedure 3. | CN(C)C[C@@H](CCc1ccccc1)NC(=O)c1n[nH]c(NC(=O)c2ccccc2Cl)c1Br | null | CC(CNC(=O)c1n[nH]c(NC(=O)c2ccccc2Cl)c1Br)N1CCCC1 | c1cn[nH]c1 | null | N1[CH:5]=[CH:4][CH:3]=N1.[N:6]1([CH:11](C)[CH2:12][NH:13][C:14]([C:16]2[C:20]([Br:21])=[C:19]([NH:22][C:23](=[O:31])[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[Cl:30])[NH:18][N:17]=2)=[O:15])[CH2:10]CC[CH2:7]1>>[CH3:10][N:6]([CH2:11][C@H:12]([NH:13][C:14]([C:16]1[C:20]([Br:21])=[C:19]([NH:22][C:23](=[O:31])[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[Cl:30])[NH:18][N:17]=1)=[O:15])[CH2:3][CH2:4][C:5]1[CH:28]=[CH:29][CH:24]=[CH:25][CH:26]=1)[CH3:7] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
786,142 | CC(=NO)C(=O)C1CCCCC1 | Cc1ccc(C=O)cc1 | null | null | ord_dataset-4ad5db8537994579bef51f16dd8bf0bd | 2007-01-01T00:08:00 | true | Analogously to the building block synthesis of 4-iodomethyl-5-phenyl-2-p-tolyloxazole, 1-cyclohexyl-1,2-propanedione-2-oxime and p-tolu-aldehyde gave 4-iodomethyl-5-cyclohexyl-2-p-tolyloxazole. | Cc1ccc(-c2nc(CI)c(C3CCCCC3)o2)cc1 | null | Cc1ccc(-c2nc(CI)c(-c3ccccc3)o2)cc1 | null | null | [I:1][CH2:2][C:3]1[N:4]=[C:5]([C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=2)[O:6][C:7]=1[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C1(C(=O)C(=NO)C)CCCCC1.C1(C)C=CC(C=O)=CC=1>>[I:1][CH2:2][C:3]1[N:4]=[C:5]([C:14]2[CH:15]=[CH:16][C:17]([CH3:20])=[CH:18][CH:19]=2)[O:6][C:7]=1[CH:8]1[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,133,628 | null | null | null | null | ord_dataset-aaeaab5f3720492494c1cbbdd0ed2820 | 2012-01-01T00:02:00 | true | The title compound was prepared from (S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-[(S)-1-(4-(4,4,5,5-tetra methyl-1,3,2-d ioxaborolan-2-yl)phenyl)ethyl]-1,3-oxazinan-2-one and 4-bromo-1-(2-methoxy-2-methyl-propyl)-1H-pyridin-2-one following a procedure analogous to that described in Example 75 Method 1. Mass spectrum (ESI+): m/z=533 [M+H]+. | COC(C)(C)Cn1ccc(-c2ccc(C(C)N3CC[C@](CC(C)(C)O)(c4ccccc4)OC3=O)cc2)cc1=O | null | COC(C)(C)Cn1ccc(Br)cc1=O | C[C@@H](c1ccc(B2OC(C)(C)C(C)(C)O2)cc1)N1CC[C@](CC(C)(C)O)(c2ccccc2)OC1=O | null | [OH:1][C:2]([CH3:35])([CH3:34])[CH2:3][C@@:4]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16](B3OC(C)(C)C(C)(C)O3)=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1.Br[C:37]1[CH:42]=[CH:41][N:40]([CH2:43][C:44]([O:47][CH3:48])([CH3:46])[CH3:45])[C:39](=[O:49])[CH:38]=1>>[OH:1][C:2]([CH3:35])([CH3:34])[CH2:3][C@@:4]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[O:9][C:8](=[O:10])[N:7]([CH:11]([C:13]2[CH:14]=[CH:15][C:16]([C:37]3[CH:42]=[CH:41][N:40]([CH2:43][C:44]([O:47][CH3:48])([CH3:46])[CH3:45])[C:39](=[O:49])[CH:38]=3)=[CH:17][CH:18]=2)[CH3:12])[CH2:6][CH2:5]1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
302,561 | null | null | null | null | ord_dataset-bfcf5a01f1a04ec585ba3f28cb93c8c9 | 1995-01-01T00:01:00 | true | Gaseous methylamine was introduced into a solution of 1.33 g (3.76 mmole) of (3S, 5S)-5-[(1S)-1-(t-butoxycarbonyl)amino-2-cyclohexylethyl]-3-isopropyldihydrofuran-2(3H)-one (prepared as described in Preparation 1) in 10 ml of methanol to ensure saturation, whilst ice-cooling. The reaction vessel was then stoppered tightly and allowed to stand overnight. At the end of this time, the solvent was removed by distillation under reduced pressure and the residue was recrystallized from hexane to afford 1.32 g (yield 91%) of the title compound as white crystals, melting at 154°-157° C. | CNC(=O)[C@@H](C[C@H](O)[C@H](CC1CCCCC1)NC(=O)OC(C)(C)C)C(C)C | null | CN | CC(C)[C@@H]1C[C@@H]([C@H](CC2CCCCC2)NC(=O)OC(C)(C)C)OC1=O | null | [CH3:1][NH2:2].[C:3]([O:7][C:8]([NH:10][C@H:11]([C@H:19]1[O:23][C:22](=[O:24])[C@H:21]([CH:25]([CH3:27])[CH3:26])[CH2:20]1)[CH2:12][CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)=[O:9])([CH3:6])([CH3:5])[CH3:4]>CO>[C:3]([O:7][C:8]([NH:10][C@@H:11]([CH2:12][CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)[C@@H:19]([OH:23])[CH2:20][C@@H:21]([CH:25]([CH3:27])[CH3:26])[C:22]([NH:2][CH3:1])=[O:24])=[O:9])([CH3:6])([CH3:5])[CH3:4] | 8 | CO | null | null | null | null | 91 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
302,915 | [Mn+4] | [O-2] | null | null | ord_dataset-bfcf5a01f1a04ec585ba3f28cb93c8c9 | 1995-01-01T00:01:00 | true | 1.0 g (0.0038 mole) of 2-cyano-1-[4-(hydroxymethyl)phenyl]indole was dissolved in 150 ml tetrahydrofuran, 10.0 g of activated manganese dioxide was added, and the mixture stirred at room temperature for 16 hours. The reaction was filtered and the filtrate evaporated to an oil, which was crystallized from a mixture of methyl-t-butyl ether and hexane 1:1 to give 0.63 g (0.0026 mole) of 1-(4-formylphenyl)-2-cyanoindole as an oil. | N#Cc1cc2ccccc2n1-c1ccc(C=O)cc1 | null | N#Cc1cc2ccccc2n1-c1ccc(CO)cc1 | null | null | [C:1]([C:3]1[N:4]([C:12]2[CH:17]=[CH:16][C:15]([CH2:18][OH:19])=[CH:14][CH:13]=2)[C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2)#[N:2]>O1CCCC1.[O-2].[O-2].[Mn+4]>[CH:18]([C:15]1[CH:16]=[CH:17][C:12]([N:4]2[C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH:11]=[C:3]2[C:1]#[N:2])=[CH:13][CH:14]=1)=[O:19] | 16 | C1CCOC1 | null | null | 25 | 68.4 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
247,387 | null | null | null | null | ord_dataset-75ca79f43dad4cc8a934fe6487fa8eb1 | 1992-01-01T00:05:00 | true | First 1.96 g (12.5 mmol) of piperidine-3-carboxylic acid ethyl ester and then 2.58 g (20 mmol) of N-ethyl-N,N-diisopropylamine are added to a solution of 3.34 g 10 mmol) of 2-[2-(p-toluenesulphonyloxy)ethyl]-benzo-1,4-dioxan in 50 ml of absolute dimethylformamide. The mixture is stirred for 16 hours at 60° and, after cooling, is concentrated by evaporation under a high vacuum. Water is added to the oily residue and extraction is carried out with diethyl ether. The combined organic phases are washed with water and extracted with 2N hydrochloric acid. The combined hydrochloric acid extracts are rendered alkaline, while cold, with sodium hydroxide solution (30% strength) and extracted with dichloromethane. The combined dichloromethane phases are dried over sodium sulphate and concentrated by evaporation in vacuo. 3.82 g (100%) of crude product are obtained which are filtered over 190 g of silica gel (0.040-0.063 mm) using ethyl acetate as the eluant. 3.70 g (96.6%) of 1-[2-(benzo-1,4-dioxan-2-yl)ethyl]-piperidine-3-carboxylic acid ethyl ester are then obtained in the form of a pale yellow oil. The 1-[2-(benzo-1,4-dioxan-2-yl)ethyl]-piperidine-3-carboxylic acid ethyl ester hydrochloride produced therefrom using hydrochloric acid in diethyl ether crystallises from ethanol/diethyl ether and melts at 162°-165°. | CCOC(=O)C1CCCN(CCC2COc3ccccc3O2)C1 | null | CCOC(=O)C1CCCNC1 | Cc1ccc(S(=O)(=O)OCCC2COc3ccccc3O2)cc1 | null | [CH2:1]([O:3][C:4]([CH:6]1[CH2:11][CH2:10][CH2:9][NH:8][CH2:7]1)=[O:5])[CH3:2].C(N(C(C)C)C(C)C)C.C1(C)C=CC(S(O[CH2:31][CH2:32][CH:33]2[O:38][C:37]3[CH:39]=[CH:40][CH:41]=[CH:42][C:36]=3[O:35][CH2:34]2)(=O)=O)=CC=1>CN(C)C=O>[CH2:1]([O:3][C:4]([CH:6]1[CH2:11][CH2:10][CH2:9][N:8]([CH2:31][CH2:32][CH:33]2[O:38][C:37]3[CH:39]=[CH:40][CH:41]=[CH:42][C:36]=3[O:35][CH2:34]2)[CH2:7]1)=[O:5])[CH3:2] | 16 | CCN(C(C)C)C(C)C | CN(C)C=O | null | null | null | 96.6 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,018,770 | null | null | null | null | ord_dataset-f024e9664ab64906a71a2ff6004cb3d0 | 2010-01-01T00:12:00 | true | To a solution of (R)-tert-butyl 2-((S)-(6-fluoro-3′-methylbiphenyl-2-yl)(2-hydroxyethoxy)methyl)morpholine-4-carboxylate (498 mg, 1.12 mmol) in dry CH2Cl2 (15 mL) was added Et3N (472 mg, 4.68 mmol) at ˜0 to −5° C. A solution of MsCl (267 mg, 2.34 mmol) in dry CH2Cl2 (10 mL) was added dropwise at the same temperature. The mixture was allowed to warm to rt gradually. Tlc showed the stating material had disappeared. Water (10 mL) was added and the aqueous layer was extracted with CH2Cl2 (3×20 mL). The combined organic layers were washed with 10% aq citric acid, satd aq NaHCO3 and brine, dried over Na2SO4, filtered and concentrated to afford crude (R)-tert-butyl 2-((S)-(6-fluoro-3′-methylbiphenyl-2-yl)(2-(methylsulfonyloxy)ethoxy)methyl)morpholine-4-carboxylate (554 mg, 95%). which was used in the next step without further purification. MS (E/Z): 524 (M+H+) | Cc1cccc(-c2c(F)cccc2[C@H](OCCOS(C)(=O)=O)[C@H]2CN(C(=O)OC(C)(C)C)CCO2)c1 | null | CS(=O)(=O)Cl | Cc1cccc(-c2c(F)cccc2[C@H](OCCO)[C@H]2CN(C(=O)OC(C)(C)C)CCO2)c1 | null | [F:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH3:14])[CH:9]=2)=[C:6]([C@H:15]([O:29][CH2:30][CH2:31][OH:32])[C@@H:16]2[O:21][CH2:20][CH2:19][N:18]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:17]2)[CH:5]=[CH:4][CH:3]=1.CCN(CC)CC.[CH3:40][S:41](Cl)(=[O:43])=[O:42].O>C(Cl)Cl>[F:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH3:14])[CH:9]=2)=[C:6]([C@H:15]([O:29][CH2:30][CH2:31][O:32][S:41]([CH3:40])(=[O:43])=[O:42])[C@@H:16]2[O:21][CH2:20][CH2:19][N:18]([C:22]([O:24][C:25]([CH3:26])([CH3:27])[CH3:28])=[O:23])[CH2:17]2)[CH:5]=[CH:4][CH:3]=1 | null | CCN(CC)CC | ClCCl | O | 25 | null | 94.5 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
672,557 | null | null | null | null | ord_dataset-e90cd41afe844e49875435eb99903799 | 2005-01-01T00:05:00 | true | A mixture of 2-bromo-1-(5-fluorobenzo[b]thiophen-2-yl)propan-1-one (0.2 g), 2-imidazolidinethione (0.08 g) and ethanol (6 ml) was heated under reflux for 10 minutes. Acetic acid (3 ml) was added, the mixture was heated under reflux for 24 hours, then the solvents were removed in vacuo. Ethanol (10 ml) was added then removed in vacuo, and the residue was dried in vacuo at 60° C. to give 3-(5-fluorobenzo[b]thiophen-2-yl)-3-methyl-5,6-dihydroimidazo[2,1-b]thiazole hydrobromide (0.2 g) as an off-white solid, 1H-nmr (DMSO-d6): δH 2.43 (3H, s, —CH3), 4.22-4.51 (4H, m, —CH2CH2—), 7.36-7.44 (1H, m, ArH), 7.79 (1H, s, ArH), 7.81 (1H, dd, J 9.6 Hz, 2.5 Hz, ArH), 8.13-8.19 (1H, m ArH), 9.3-9.9 (1H, br, H+). | Br | CC1(c2cc3cc(F)ccc3s2)CSC2=NCCN21 | CCO | CC(Br)C(=O)c1cc2cc(F)ccc2s1 | S=C1NCCN1 | [Br:1][CH:2](C)[C:3]([C:5]1[S:9][C:8]2[CH:10]=[CH:11][C:12]([F:14])=[CH:13][C:7]=2[CH:6]=1)=O.[NH:16]1[CH2:20][CH2:19][NH:18][C:17]1=[S:21].[CH2:22](O)C>C(O)(=O)C>[BrH:1].[F:14][C:12]1[CH:11]=[CH:10][C:8]2[S:9][C:5]([C:3]3([CH3:2])[CH2:22][S:21][C:17]4=[N:18][CH2:19][CH2:20][N:16]34)=[CH:6][C:7]=2[CH:13]=1 | null | CC(=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 |
1,586,963 | CN(C)C(On1nnc2cccnc21)=[N+](C)C | Cl | F[P-](F)(F)(F)(F)F | null | ord_dataset-380e279f82154dba9e08ab51b3bdd08a | 2015-01-01T00:05:00 | true | To a solution of 4-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-6-methyl-5-oxo-2,3,4,5-tetrahydro-1,4-benzoxazepine-7-carboxylic acid (130f, 0.17 g, 0.38 mmol), dimethylamine hydrochloride (47 mg, 0.57 mmol) and DIPEA (0.25 g, 1.90 mmol) in DMF (10 mL) was added HATU (0.29 g, 0.76 mmol). The mixture was stirred at room temperature under N2 for 5 hours. To the reaction mixture was added H2O (30 mL). The mixture was extracted with EtOAc (2×20 mL). The combined organic layers were washed with brine (4×30 mL), dried over Na2SO4, and concentrated under vacuum. The residue was purified by column chromatography (petroleum ether/EtOAc, 1/1) to give 4-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-N,6-dimethyl-5-oxo-2,3,4,5-tetrahydro-1,4-benzoxazepine-7-carboxamide (130 g, 0.17 g, 94.6%) as a white solid. | CNC(=O)c1ccc2c(c1C)C(=O)N(Cc1c(C)cc(C)nc1OCc1ccccc1)CCO2 | null | Cc1cc(C)c(CN2CCOc3ccc(C(=O)O)c(C)c3C2=O)c(OCc2ccccc2)n1 | CNC | null | [CH2:1]([O:8][C:9]1[C:14]([CH2:15][N:16]2[C:22](=[O:23])[C:21]3[C:24]([CH3:31])=[C:25]([C:28](O)=[O:29])[CH:26]=[CH:27][C:20]=3[O:19][CH2:18][CH2:17]2)=[C:13]([CH3:32])[CH:12]=[C:11]([CH3:33])[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH3:35][NH:36]C.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O>[CH2:1]([O:8][C:9]1[C:14]([CH2:15][N:16]2[C:22](=[O:23])[C:21]3[C:24]([CH3:31])=[C:25]([C:28]([NH:36][CH3:35])=[O:29])[CH:26]=[CH:27][C:20]=3[O:19][CH2:18][CH2:17]2)=[C:13]([CH3:32])[CH:12]=[C:11]([CH3:33])[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1 | 5 | O | CCN(C(C)C)C(C)C | CN(C)C=O | 25 | null | 74,445.7 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,518,592 | O=C([O-])[O-] | [K+] | null | null | ord_dataset-8c74302143c04eb9983e4b3a7ead2d72 | 2014-01-01T00:12:00 | true | A mixture of the 7-chloro-2-iodothieno[3,2-b]pyridine (23) (Ragan J. A. et al, Organic Process Research and Development 2003, 7, 676-683) (7.0 g, 23.7 mmol), 2-fluoro-4-nitrophenol (3) (11.15 g, 71.1 mmol), K2CO3 (13.08 g, 94.8 mmol) in Ph2O (30 ml) was heated at 200° C. for 3 h. The reaction mixture was cooled to room temperature, diluted with DCM and filtered; the filtrate was collected and then concentrated. The resultant solid was triturated with diethyl ether, to afford intermediate 24 (7.3 g, 74% yield), which was used directly in the next step with no additional purification. MS (m/z): 417.0 (M+H). | O=[N+]([O-])c1ccc(Oc2ccnc3cc(I)sc23)c(F)c1 | null | Clc1ccnc2cc(I)sc12 | O=[N+]([O-])c1ccc(O)c(F)c1 | null | Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([I:11])[S:10][C:3]=12.[N+:12]([C:15]1[CH:20]=[CH:19][C:18]([OH:21])=[C:17]([F:22])[CH:16]=1)([O-:14])=[O:13].C([O-])([O-])=O.[K+].[K+]>O(C1C=CC=CC=1)C1C=CC=CC=1.C(Cl)Cl>[F:22][C:17]1[CH:16]=[C:15]([N+:12]([O-:14])=[O:13])[CH:20]=[CH:19][C:18]=1[O:21][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([I:11])[S:10][C:3]=12 | null | ClCCl | c1ccc(Oc2ccccc2)cc1 | null | 25 | 74 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
15,773 | null | null | null | null | ord_dataset-b971427c0b944c56b63bb2356fa8ca69 | 1976-01-01T00:11:00 | true | 4-Hydroxy-2-methyl-N-(3-methyl-5-isothiazolyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide-1,1-dioxide was prepared analogous to Example 22 from 4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid methylester-1,1-dioxide and 5-amino-3-methyl-isothiazole. Yield: 44% of theory; m.p. 268° C (decomp.; from ethylene chloride). | Cc1cc(NC(=O)C2=C(O)c3ccc4ccccc4c3S(=O)(=O)N2C)sn1 | null | COC(=O)C1=C(O)c2ccc3ccccc3c2S(=O)(=O)N1C | Cc1cc(N)sn1 | null | CO[C:3]([C:5]1[N:6]([CH3:22])[S:7](=[O:21])(=[O:20])[C:8]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH:13]=[CH:12][C:9]=2[C:10]=1[OH:11])=[O:4].[NH2:23][C:24]1[S:28][N:27]=[C:26]([CH3:29])[CH:25]=1>C(Cl)CCl>[OH:11][C:10]1[C:9]2[CH:12]=[CH:13][C:14]3[C:19]([C:8]=2[S:7](=[O:20])(=[O:21])[N:6]([CH3:22])[C:5]=1[C:3]([NH:23][C:24]1[S:28][N:27]=[C:26]([CH3:29])[CH:25]=1)=[O:4])=[CH:18][CH:17]=[CH:16][CH:15]=3 | null | ClCCCl | null | null | null | 44 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
740,834 | null | null | null | null | ord_dataset-437aa6654d5044ddaef3346dc4c6e08a | 2006-01-01T00:11:00 | true | 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (78 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (120 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-dimethylamino-α-methylbenzyl alcohol (65 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (61 mg, yield 44%). | COc1cc2nccc(Oc3ccc(NC(=O)OC(C)c4cccc(N(C)C)c4)cc3)c2cc1OC | null | COc1cc2nccc(Oc3ccc(N)cc3)c2cc1OC | O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl | CC(O)c1cccc(N(C)C)c1 | [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[CH:18][CH:17]=1.C1(C)C=CC=CC=1.C(N(CC)CC)C.Cl[C:38](Cl)([O:40]C(=O)OC(Cl)(Cl)Cl)Cl.[CH3:49][N:50]([CH3:60])[C:51]1[CH:52]=[C:53]([CH:57]=[CH:58][CH:59]=1)[CH:54]([OH:56])[CH3:55]>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:22]=[CH:21][C:19]([NH:20][C:38](=[O:40])[O:56][CH:54]([C:53]2[CH:57]=[CH:58][CH:59]=[C:51]([N:50]([CH3:49])[CH3:60])[CH:52]=2)[CH3:55])=[CH:18][CH:17]=1 | null | CCN(CC)CC | ClCCl | Cc1ccccc1 | 25 | 47.5 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
806,169 | CCOc1ccc(Br)cc1F | [BH4-] | [Na+] | null | ord_dataset-da49b0378abf41bf92ab8ecdd3feb28b | 2008-01-01T00:02:00 | true | 2.00 g (5.24 mmol) of 3-benzyloxy-8-ethoxy-4,7-difluoro-6H-benzo[c]chromen-6-one, the compound of Example 841, were dissolved in 12 ml of THF, and 2.37 ml (23.0 mmol) of boron trifluoride/THF complex were added with ice-cooling. 24 ml of ethylene glycol dimethyl ether and then in portions 530 mg of sodium borohydride were subsequently added. The mixture was subsequently stirred at room temperature for 18 hours and then transferred onto ice. The mixture was subjected to conventional purification, giving 1.5 g (78% of theory) of 3-benzyloxy-8-ethoxy-4,7-difluoro-6H-benzo[c]chromene as colourless crystals. These were dissolved in THF, hydrogenated at a pressure of 1 bar in the presence of 0.6 g of Pd/C (5%), filtered and evaporated, giving 1.2 g (99% of theory) of 8-ethoxy-4,7-difluoro-3-hydroxy-6H-benzo[c]chromene as colourless crystals. | CCOc1ccc2c(c1F)COc1c-2ccc(OCc2ccccc2)c1F | null | CCOc1ccc2c(c1F)c(=O)oc1c(F)c(OCc3ccccc3)ccc12 | null | null | [CH2:1]([O:8][C:9]1[C:18]([F:19])=[C:17]2[C:12]([C:13]3[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH3:27])=[C:21]([F:28])[C:14]=3[C:15](=O)[O:16]2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.BrC1C=CC(OCC)=C(F)C=1.COCCOC.[BH4-].[Na+]>C1COCC1>[CH2:1]([O:8][C:9]1[C:18]([F:19])=[C:17]2[C:12]([C:13]3[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH3:27])=[C:21]([F:28])[C:14]=3[CH2:15][O:16]2)=[CH:11][CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1 | 18 | C1CCOC1 | COCCOC | null | 25 | null | 77.7 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,347,214 | [K+] | null | null | null | ord_dataset-6034127657614f02860ed057b62b882e | 2013-01-01T00:10:00 | true | N-[2-(2-Mercapto-7,8-dihydro-6H-indeno[5,4-d][1,3]oxazol-8-yl)ethyl]acetamide (108 mg, 0.391 mmol) was dissolved in N,N-dimethylformamide (4 mL), iodomethane (48.6 μL, 0.782 mmol) and potassium carbonate (59.4 mg, 0.430 mmol) were added, and the mixture was stirred at room temperature for 15 min. The reaction solution was diluted with diethyl ether, washed with saturated aqueous sodium hydrogencarbonate solution and saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane=50/50→100/0) to give the title compound (81.2 mg, yield 72%). | CSc1nc2ccc3c(c2o1)C(CCNC(C)=O)CC3 | null | CC(=O)NCCC1CCc2ccc3nc(S)oc3c21 | O=C([O-])[O-] | null | [SH:1][C:2]1[O:3][C:4]2[C:13]3[CH:12]([CH2:14][CH2:15][NH:16][C:17](=[O:19])[CH3:18])[CH2:11][CH2:10][C:9]=3[CH:8]=[CH:7][C:5]=2[N:6]=1.IC.[C:22](=O)([O-])[O-].[K+].[K+]>CN(C)C=O.C(OCC)C>[CH3:22][S:1][C:2]1[O:3][C:4]2[C:13]3[CH:12]([CH2:14][CH2:15][NH:16][C:17](=[O:19])[CH3:18])[CH2:11][CH2:10][C:9]=3[CH:8]=[CH:7][C:5]=2[N:6]=1 | 0.25 | CI | CN(C)C=O | CCOCC | 25 | null | 71.5 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
186,616 | O=C1C=CC(=O)O1 | null | null | null | ord_dataset-754e10d30fb249229e130865010ab25b | 1989-01-01T00:03:00 | true | In 200 ml of methyl ethyl ketone were dissolved 18.14 g of maleic anhydride and 21.86 g of α-methylstyrene, and to the solution was added 1.82 g of azobisisobutylnitrile (AIBN). The resulting mixture was heated at 60° C. for 7 hours under nitrogen atmosphere for performing polymerization. The reaction solution was then dropwise added to 500 ml of ethyl ether under stirring to precipitate a polymer. Thus precipitated polymer was collected by filtration and purified by repeating twice the THF dissolution-ethyl ether precipitation procedure described in Example 1. Thus purified polymer was dried under vacuum at 100° C. for 24 hours to give 17.0 g of a maleic anhydride-styrene copolymer. It was confiremed by elementary analysis that the copolymerization ratio was approximately 1:1. Mn was 11,730. | C=Cc1ccccc1 | null | C=C(C)c1ccccc1 | null | null | [C:1]1(=[O:7])[O:6][C:4](=[O:5])[CH:3]=[CH:2]1.[CH3:8][C:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=C.C(OCC)C>C(C(C)=O)C>[CH2:8]=[CH:9][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[CH:2]1[C:1](=[O:7])[O:6][C:4](=[O:5])[CH:3]=1 | null | CCOCC | CCC(C)=O | null | 60 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
603,290 | CCN=C=NCCCN(C)C | Cl | On1nnc2ccccc21 | null | ord_dataset-82e842e611ef4a05b6e7f9ea0a46d52d | 2003-01-01T00:07:00 | true | 5-[5-(2,6-Dimethyl-phenylmethanesulfonyl)-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (120 mg, 0.26 mmol) was coupled with (S)-2-pyrrolidin-1-ylmethyl-pyrrolidine (50 mg, 1.2 eq.), HOBt (42 mg, 1.2 eq.), EDAC.HCl (60 mg, 1.2 eq.) and TEA (3 eq.) in acetonitrile: DMF (3:1) to give the titled compound. | Cc1cccc(C)c1CS(=O)(=O)c1ccc2c(c1)/C(=C/c1[nH]c(C)c(C(=O)N3CCC[C@H]3CN3CCCC3)c1C)C(=O)N2 | null | Cc1cccc(C)c1CS(=O)(=O)c1ccc2c(c1)/C(=C/c1[nH]c(C)c(C(=O)O)c1C)C(=O)N2 | C1CN[C@H](CN2CCCC2)C1 | null | [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[CH2:9][S:10]([C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][C:17](=[O:22])/[C:16]/2=[CH:23]\[C:24]1[NH:28][C:27]([CH3:29])=[C:26]([C:30](O)=[O:31])[C:25]=1[CH3:33])(=[O:12])=[O:11].[N:34]1([CH2:39][C@@H:40]2[CH2:44][CH2:43][CH2:42][NH:41]2)[CH2:38][CH2:37][CH2:36][CH2:35]1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>C(#N)C.CN(C=O)C>[CH3:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([CH3:1])[C:3]=1[CH2:9][S:10]([C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][C:17](=[O:22])/[C:16]/2=[CH:23]\[C:24]1[NH:28][C:27]([CH3:29])=[C:26]([C:30]([N:41]2[CH2:42][CH2:43][CH2:44][C@H:40]2[CH2:39][N:34]2[CH2:38][CH2:37][CH2:36][CH2:35]2)=[O:31])[C:25]=1[CH3:33])(=[O:11])=[O:12] | null | CC#N | CN(C)C=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 |
1,505,053 | On1nnc2ccccc21 | null | null | null | ord_dataset-1a1aa5d1c3224edca0aec6e3398da985 | 2014-01-01T00:11:00 | true | (4-acetyl-phenylazo)-(3,3-dimethyl-3,4-dihydro-2H-isoquinoline-1-ylidene)-acetic acid, dimethylamine, HOBt (Advanced ChemTech Corp., USA) and triethylamine are dissolved in DMF, a dichloromethane solution of HETU (Advanced ChemTech Corp., USA) is added, and then the mixture is stirred at room temperature. The stirred and blended solvent is washed with a saturated aqueous sodium chloride solution and a 5% aqueous sodium hydrogen carbonate solution. The reaction product is dried with anhydrous sodium sulfate and filtered and, then, the solvent is removed by reducing the pressure. The residue containing the reaction product is purified by column chromatography to obtain the title compound. | CC(=O)c1ccc(N=NC(C(=O)N(C)C)=C2NC(C)(C)Cc3ccccc32)cc1 | null | CNC | CC(=O)c1ccc(N=NC(C(=O)O)=C2NC(C)(C)Cc3ccccc32)cc1 | null | [C:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]=[N:11][C:12](=[C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH2:19][C:18]([CH3:27])([CH3:26])[NH:17]2)[C:13](O)=[O:14])=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[CH3:28][NH:29][CH3:30].C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C>CN(C=O)C.ClCCl>[C:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]=[N:11][C:12](=[C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH2:19][C:18]([CH3:26])([CH3:27])[NH:17]2)[C:13]([N:29]([CH3:30])[CH3:28])=[O:14])=[CH:6][CH:5]=1)(=[O:3])[CH3:2] | null | CN(C)C=O | ClCCl | CCN(CC)CC | 25 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,477,142 | null | null | null | null | ord_dataset-c3c1091f873b4f40827973a6f1f9b685 | 2014-01-01T00:09:00 | true | Using a procedure similar to that described in Example 1, except using 2-amino-3-(4-bromo-5,7-dichloro-2H-benzotriazol-2-yl)-2-methylpropionitrile and 4-trifluoromethylthiobenzoyl chloride, the title compound was isolated as a white solid (110 mg, described in Example 55). MS (ES): M/Z [M+H]=552. NMR: (400 MHz, DMSO-d6): 1.75 (s, 3H), 5.44 (d, J=13.3 Hz, 1H), 5.60 (d, J=13.7 Hz, 1H), 7.75-8.04 (m, 5H) and 8.91 (s, 1H). 19F NMR (376 MHz, DMSO-d6): −42.0 (s, 3F). | CC(C#N)(Cn1nc2c(Cl)cc(Cl)c(Br)c2n1)NC(=S)c1ccc(C(F)(F)F)cc1 | null | FC(F)(F)c1ccc(C(=S)Cl)cc1 | CC(N)(C#N)Cn1nc2c(Cl)cc(Cl)c(Br)c2n1 | null | [NH2:1][C:2]([CH3:18])([CH2:5][N:6]1[N:10]=[C:9]2[C:11]([Cl:17])=[CH:12][C:13]([Cl:16])=[C:14]([Br:15])[C:8]2=[N:7]1)[C:3]#[N:4].[F:19][C:20]([F:31])([F:30])[C:21]1[CH:29]=[CH:28][C:24]([C:25](Cl)=[S:26])=[CH:23][CH:22]=1>>[Br:15][C:14]1[C:8]2[C:9](=[N:10][N:6]([CH2:5][C:2]([NH:1][C:25](=[S:26])[C:24]3[CH:23]=[CH:22][C:21]([C:20]([F:19])([F:30])[F:31])=[CH:29][CH:28]=3)([C:3]#[N:4])[CH3:18])[N:7]=2)[C:11]([Cl:17])=[CH:12][C:13]=1[Cl:16] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
161,729 | COS(=O)(=O)[O-] | null | null | null | ord_dataset-c34472859da14a81bfe0f74e60f15c43 | 1987-01-01T00:08:00 | true | A mixture of 2-methyl-3-trimethylammoniomethylimidazo[2,1-a]isoquinoline methylsulfate (3 g) and 2-methylimidazole (1.6 g) in ethanol (50 ml) was refluxed with stirring for 4 hours and evaporated in vacuo. To the residue was added water and the resulting precipitates were collected by filtration, dried and recrystallized from ethyl acetate to give 2-methyl-3-(2-methyl-1-imidazolylmethyl)imidazo[2,1-a]isoquinoline (0.85 g). | Cc1nc2c3ccccc3ccn2c1CC1(C)N=CC=N1 | null | Cc1ncc[nH]1 | Cc1nc2c3ccccc3ccn2c1C[N+](C)(C)C | null | COS([O-])(=O)=O.[CH3:7][C:8]1[N:9]=[C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH:13]=[CH:12][N:11]2[C:20]=1[CH2:21][N+](C)(C)C.[CH3:26][C:27]1[NH:28][CH:29]=[CH:30][N:31]=1>C(O)C>[CH3:7][C:8]1[N:9]=[C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH:13]=[CH:12][N:11]2[C:20]=1[CH2:21][C:27]1([CH3:26])[N:31]=[CH:30][CH:29]=[N:28]1 | 4 | CCO | null | null | null | 37.5 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
693,606 | CCN=C=N | Cl | On1nnc2ccccc21 | null | ord_dataset-35824232b132464aa99e71aba765981d | 2005-01-01T00:12:00 | true | 10-(4-Cyclohex-1-en-1-yl-3-methyl-benzoyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid (0.300 g, 0.703 mmol) of Example 5 Step E, D-serine methyl ester hydrochloride (0.131 g, 0.844 mmol), 1-hydroxy benzotriazole (0.104 g, 0.773 mmol) and 1-[3-dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.148 g, 0.773 mmol) were combined in amine-free N,N-dimethylformamide (2.8 mL), followed by the addition of N,N-diisopropylethylamine (0.307 mL, 1.76 mmol). The reaction was stirred at room temperature for 12 hours, then diluted with ethyl acetate and washed with water, 1 N hydrochloric acid, 1 N sodium hydroxide and brine. The combined aqueous washings were saturated with sodium chloride, and extracted with ethyl acetate. The organic phases were combined, dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by flash column chromatography on silica gel eluting with 10% methanol in chloroform, to afford 0.320 g of the title compound as a pale yellow solid. | COC(=O)[C@@H](CO)NC(=O)c1ccc2n1Cc1ccccc1N(C(=O)c1ccc(C3=CCCCC3)c(C)c1)C2 | null | COC(=O)[C@H](N)CO | Cc1cc(C(=O)N2Cc3ccc(C(=O)O)n3Cc3ccccc32)ccc1C1=CCCCC1 | null | [C:1]1([C:7]2[CH:31]=[CH:30][C:10]([C:11]([N:13]3[C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=4[CH2:17][N:16]4[C:24]([C:27](O)=[O:28])=[CH:25][CH:26]=[C:15]4[CH2:14]3)=[O:12])=[CH:9][C:8]=2[CH3:32])[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1.Cl.[CH3:34][O:35][C:36](=[O:41])[C@@H:37]([CH2:39][OH:40])[NH2:38].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=N)C.C(N(CC)C(C)C)(C)C>C(OCC)(=O)C>[CH3:34][O:35][C:36](=[O:41])[C@H:37]([NH:38][C:27]([C:24]1[N:16]2[C:15]([CH2:14][N:13]([C:11](=[O:12])[C:10]3[CH:30]=[CH:31][C:7]([C:1]4[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=4)=[C:8]([CH3:32])[CH:9]=3)[C:19]3[CH:18]=[CH:23][CH:22]=[CH:21][C:20]=3[CH2:17]2)=[CH:26][CH:25]=1)=[O:28])[CH2:39][OH:40] | 12 | CCN(C(C)C)C(C)C | CCOC(C)=O | null | 25 | null | 86.3 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,261,873 | null | null | null | null | ord_dataset-266f60b4555945d6afb2d2bdf5fa04e0 | 2013-01-01T00:02:00 | true | To a stirred solution of 1-Boc-piperazine (0.50 g, 2.7 mmol) and diisopropylethylamine (1.75 g, 13.5 mmol) in dichloromethane at 0° C. was added a solution of 2-trifluoromethylbenzoyl chloride (0.626 g, 3.0 mmol). The resulting mixture was stirred at room temperature for 20 h and then quenched with water (25 mL). The organic phase was washed with water, dried over anhydrous Na2SO4, filtered and concentrated in vacuo to yield 4-(2-trifluoromethylbenzoyl)piperazine-1-carboxylic acid tent-butyl ester as a pale brown oil (0.948 g, 98% yield). 1H NMR (300 MHz, CDCl3) δ 7.69, 7.54, 7.30, 3.77, 3.51, 3.33, 3.14, 1.45. | O=C(O)N1CCN(C(=O)c2ccccc2C(F)(F)F)CC1 | null | O=C(Cl)c1ccccc1C(F)(F)F | CC(C)(C)OC(=O)N1CCNCC1 | null | [C:1]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)([O:3]C(C)(C)C)=[O:2].C(N(C(C)C)CC)(C)C.[F:23][C:24]([F:35])([F:34])[C:25]1[CH:33]=[CH:32][CH:31]=[CH:30][C:26]=1[C:27](Cl)=[O:28]>ClCCl>[F:23][C:24]([F:34])([F:35])[C:25]1[CH:33]=[CH:32][CH:31]=[CH:30][C:26]=1[C:27]([N:11]1[CH2:10][CH2:9][N:8]([C:1]([OH:3])=[O:2])[CH2:13][CH2:12]1)=[O:28] | 20 | ClCCl | CCN(C(C)C)C(C)C | null | 25 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,589,305 | [H-] | [Na+] | null | null | ord_dataset-e8c6a25568b64529b960953990e6921f | 2015-01-01T00:06:00 | true | To a solution of NaH (60% dispersed in oil, 32 mg, 0.81 mmo) in THF (4 mL) at 0° C. was added alcohol 1 (180 mg, 0.62 mmol) in THF (1 mL) and the reaction mixture was stirred for 30 min at this temperature. Then 3-pyridyl isothiocyanate (169 mg, 124 mmol) in THF (1 mL) was added and stirred at rt. After stirring for 12 h, the reaction mixture was quenched water and extracted with EtOAc (3×). The organic layer was dried and concentrated to get a residue, which was purified by column chromatography (Hexane/EtOAc) to yield thiocarbamate 38a as a viscous liquid (179 mg, 70%). TLC Rf: 0.23 (20% EtOAc/hexanes); 1H NMR (300 MHz, CDCl3): δ 8.55 (d, 1H), 8.40 (d, 1H), 7.95 (m, 1H), 7.30 (m, 2H), 5.49 (t, 1H), 5.11 (m, 3H), 4.70 (d, 2H), 2.16-1.19 (m, 12H), 1.76 (s, 3H), 1.68 (s, 3H), 1.60 (s, 9H); LCMS: MS (m/z): 427 (M+H). | CC(C)=CCC/C(C)=C/CC/C(C)=C/CC/C(C)=C/COC(=S)Nc1cccnc1 | null | S=C=Nc1cccnc1 | CC(C)=CCC/C(C)=C/CC/C(C)=C/CC/C(C)=C/CO | null | [H-].[Na+].[CH2:3]([CH2:13]/[C:14](/[CH3:23])=[CH:15]/[CH2:16][CH2:17]/[C:18](/[CH3:22])=[CH:19]/[CH2:20][OH:21])/[CH:4]=[C:5](/[CH2:7][CH2:8][CH:9]=[C:10]([CH3:12])[CH3:11])\[CH3:6].[N:24]1[CH:29]=[CH:28][CH:27]=[C:26]([N:30]=[C:31]=[S:32])[CH:25]=1>C1COCC1>[N:24]1[CH:29]=[CH:28][CH:27]=[C:26]([NH:30][C:31](=[S:32])[O:21][CH2:20]/[CH:19]=[C:18](\[CH3:22])/[CH2:17][CH2:16]/[CH:15]=[C:14](\[CH3:23])/[CH2:13][CH2:3]/[CH:4]=[C:5](\[CH3:6])/[CH2:7][CH2:8][CH:9]=[C:10]([CH3:12])[CH3:11])[CH:25]=1 | 0.5 | C1CCOC1 | null | null | null | 67.7 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,117,117 | null | null | null | null | ord_dataset-4226e9b4f9f845db967ed997270dcafc | 2011-01-01T00:12:00 | true | Using general procedure 2 with [(R)-2-(2-fluoro-phenyl)-1-(methoxy-methyl-carbamoyl)-ethyl]-carbamic acid tert-butyl ester (1.5 g, 4.6 mmol) and N-tert-butyl-2-chloro-6-methyl-benzamide (1.5 g, 4.6 mmol), followed by purification by silica gel flash column chromatography gives the title compound. | CC(C)(C)NC(=O)c1c(Cl)cccc1CC(=O)[C@@H](Cc1ccccc1F)NC(=O)OC(C)(C)C | null | Cc1cccc(Cl)c1C(=O)NC(C)(C)C | CON(C)C(=O)[C@@H](Cc1ccccc1F)NC(=O)OC(C)(C)C | null | [C:1]([O:5][C:6](=[O:23])[NH:7][C@@H:8]([C:17](=[O:22])N(OC)C)[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[F:16])([CH3:4])([CH3:3])[CH3:2].[C:24]([NH:28][C:29](=[O:38])[C:30]1[C:35]([CH3:36])=[CH:34][CH:33]=[CH:32][C:31]=1[Cl:37])([CH3:27])([CH3:26])[CH3:25]>>[C:1]([O:5][C:6](=[O:23])[NH:7][C@H:8]([CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[F:16])[C:17](=[O:22])[CH2:36][C:35]1[CH:34]=[CH:33][CH:32]=[C:31]([Cl:37])[C:30]=1[C:29](=[O:38])[NH:28][C:24]([CH3:26])([CH3:25])[CH3:27])([CH3:2])([CH3:3])[CH3:4] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,361,615 | null | null | null | null | ord_dataset-d932d1d683704a8bad3d064bcb197acc | 2013-01-01T00:11:00 | true | A solution of 2-butyl-1-[4-(4-chloro-phenoxy)-phenyl]-4-[4-((S)-1-oxiranylmethoxy)-phenyl]-1H-imidazole (from intermediate A3) in 3 mL of dimethylamine in THF (2M) was stirred at 76° C. for 1 h in a microwave reactor. Upon completion (determined by LC/MS), the reaction was evaporated in vacuo and purified by silica gel flash column chromatography using a gradient of EtOAc to 96% EtOAc/(2M NH3/MeOH) as an eluent to afford (S)-1-(4-{2-butyl-1-[4-(4-chloro-phenoxy)-phenyl]-1H-imidazol-4-yl}-phenoxy)-3-dimethylamino-propan-2-ol. | CCCCc1nc(-c2ccc(OC[C@@H](O)CN(C)C)cc2)cn1-c1ccc(Oc2ccc(Cl)cc2)cc1 | null | CCCCc1nc(-c2ccc(OC[C@@H]3CO3)cc2)cn1-c1ccc(Oc2ccc(Cl)cc2)cc1 | CNC | null | [CH2:1]([C:5]1[N:6]([C:21]2[CH:26]=[CH:25][C:24]([O:27][C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=3)=[CH:23][CH:22]=2)[CH:7]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][C@@H:18]3[CH2:20][O:19]3)=[CH:12][CH:11]=2)[N:9]=1)[CH2:2][CH2:3][CH3:4].[CH3:35][NH:36][CH3:37]>C1COCC1>[CH2:1]([C:5]1[N:6]([C:21]2[CH:22]=[CH:23][C:24]([O:27][C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=3)=[CH:25][CH:26]=2)[CH:7]=[C:8]([C:10]2[CH:11]=[CH:12][C:13]([O:16][CH2:17][C@@H:18]([OH:19])[CH2:20][N:36]([CH3:37])[CH3:35])=[CH:14][CH:15]=2)[N:9]=1)[CH2:2][CH2:3][CH3:4] | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,071,431 | null | null | null | null | ord_dataset-5df93261afc143c3ae919a57ff4fc1d4 | 2011-01-01T00:07:00 | true | 0.63 g of 6-(2H-tetrazol-5-yl)-2,2′-bipyridine was dissolved in 10 ml of dehydrated pyridine, and 0.29 g of isophthaloyl dichloride was gradually added. Temperature was elevated to 115° C., and stirring was conducted for 6 hours under reflux. After cooling to room temperature, the reaction solution was poured into water, and a precipitated white solid was taken out by suction filtration, and washed with water. The solid obtained was vacuum dried at 80° C. for 20 hours, and purified with column chromatography (carrier: silica gel, eluting solution: chloroform/methanol=20/1) to obtain 0.62 g (yield 81%) of BpyOXDm. The product was identified with NMR analysis. The result of NMR analysis (CDCl3) was as follows. 9.071 ppm (1H), 8.639-8.714 ppm (6H), 8.325-8.477 ppm (4H), 8.037 ppm (2H), 7.756-7.854 ppm (3H), 7.330 ppm (2H). | c1ccc(-c2cccc(-c3nnc(-c4cccc(-c5nnc(-c6cccc(-c7ccccn7)n6)o5)c4)o3)n2)nc1 | null | c1ccc(-c2cccc(-c3nn[nH]n3)n2)nc1 | O=C(Cl)c1cccc(C(=O)Cl)c1 | null | N1N[N:3]=[N:4][C:5]=1[C:6]1[N:11]=[C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)[CH:9]=[CH:8][CH:7]=1.[C:18](Cl)(=[O:28])[C:19]1[CH:27]=[CH:26][CH:25]=[C:21]([C:22](Cl)=[O:23])[CH:20]=1.O>N1C=CC=CC=1>[N:11]1[C:6]([C:5]2[O:28][C:18]([C:19]3[CH:27]=[CH:26][CH:25]=[C:21]([C:22]4[O:23][C:5]([C:6]5[N:11]=[C:10]([C:12]6[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=6)[CH:9]=[CH:8][CH:7]=5)=[N:4][N:3]=4)[CH:20]=3)=[N:3][N:4]=2)=[CH:7][CH:8]=[CH:9][C:10]=1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=1 | 6 | O | c1ccncc1 | null | 25 | null | 81 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
517,739 | Cl | null | null | null | ord_dataset-a495451286334c5c9bbcbd48a00c1350 | 2001-01-01T00:09:00 | true | A mixture of N-[(3RS)-1-(3-azabicyclo[3.2.2]non-3-yl)carbonylmethyl-2,3-dihydro-9-methyl-5-(2-fluorophenyl)-2-oxo-1H-1,4-benzodiazepin-3-yl]-N′-(3-acetylphenyl)urea (217 mg) and hydroxylamine-hydrochloride (124 mg), triethylamine (180 mg) in tetrahydrofuran (4 ml) was stirred at room temperature overnight. Ethyl acetate and 1N aqueous hydrochloric acid solution were added the reaction mixture. The separated organic layer was washed with 1N aqueous hydrochloric acid twice, saturated aqueous sodium bicarbonate and brine successively and then dried over magnesium sulfate. The solvent was evaporated in vacuo to afford N-[(3RS)-1-(3-azabicyclo[3.2.2]non-3-yl)carbonylmethyl-2,3-dihydro-9-methyl-5-(2-fluorophenyl)-2-oxo-1H-1,4-benzodiazepin-3-yl]-N′-[3-(1-hydroxyiminoethyl)phenyl]urea (235.0 mg) as a crystalline powder. | CC(=NO)c1cccc(NC(=O)NC2N=C(c3ccccc3F)c3cccc(C)c3N(CC(=O)N3CC4CCC(CC4)C3)C2=O)c1 | null | NO | CC(=O)c1cccc(NC(=O)NC2N=C(c3ccccc3F)c3cccc(C)c3N(CC(=O)N3CC4CCC(CC4)C3)C2=O)c1 | null | [CH:1]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[CH2:4][N:3]([C:10]([CH2:12][N:13]1[C:19]3[C:20]([CH3:24])=[CH:21][CH:22]=[CH:23][C:18]=3[C:17]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[F:31])=[N:16][CH:15]([NH:32][C:33]([NH:35][C:36]3[CH:41]=[CH:40][CH:39]=[C:38]([C:42](=O)[CH3:43])[CH:37]=3)=[O:34])[C:14]1=[O:45])=[O:11])[CH2:2]2.Cl.[NH2:47][OH:48].C(N(CC)CC)C.Cl>O1CCCC1.C(OCC)(=O)C>[CH:5]12[CH2:6][CH2:7][CH:1]([CH2:9][CH2:8]1)[CH2:2][N:3]([C:10]([CH2:12][N:13]1[C:19]3[C:20]([CH3:24])=[CH:21][CH:22]=[CH:23][C:18]=3[C:17]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[F:31])=[N:16][CH:15]([NH:32][C:33]([NH:35][C:36]3[CH:41]=[CH:40][CH:39]=[C:38]([C:42](=[N:47][OH:48])[CH3:43])[CH:37]=3)=[O:34])[C:14]1=[O:45])=[O:11])[CH2:4]2 | 8 | CCOC(C)=O | CCN(CC)CC | C1CCOC1 | 25 | 105.7 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
964,465 | null | null | null | null | ord_dataset-03ba810b7f464a06b5d8787af2e8b64e | 2010-01-01T00:06:00 | true | The bromination of 2-isobutyl-2-methyl-cyclohexanone takes place in a manner similar to that described above for the preparation of 2-bromo-4-isopropyl-cyclohexanone. The title compound is reacted as a crude product without further characterization. | CC(C)CC1(C)CCCC(Br)C1=O | null | CC(C)CC1(C)CCCCC1=O | CC(C)C1CCC(=O)C(Br)C1 | null | [CH2:1]([C:5]1([CH3:12])[CH2:10][CH2:9][CH2:8][CH2:7][C:6]1=[O:11])[CH:2]([CH3:4])[CH3:3].[Br:13]C1CC(C(C)C)CCC1=O>>[Br:13][CH:7]1[C:6](=[O:11])[C:5]([CH2:1][CH:2]([CH3:4])[CH3:3])([CH3:12])[CH2:10][CH2:9][CH2:8]1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,685,231 | [Ni] | N | null | null | ord_dataset-3953983e052a4076aa7cc0880b79cb8b | 2016-01-01T00:01:00 | true | To a solution of 2,6-dimethyl-2H-indazole-7-carbonitrile (1 equiv.) in methanol and aq. ammonia solution (9:1), catalytic amount of Raney Nickel was added. Reaction mass was stirred at room temperature under hydrogen pressure (balloon pressure) for 2-5 h. On completion of reaction, it was filtered through celite bed and filtrate was concentrated under reduce pressure to afford the title compound (quant. yield). | Cc1ccc2cn(C)nc2c1CN | null | Cc1ccc2cn(C)nc2c1C#N | null | null | [CH3:1][N:2]1[CH:10]=[C:9]2[C:4]([C:5]([C:12]#[N:13])=[C:6]([CH3:11])[CH:7]=[CH:8]2)=[N:3]1>CO.N.[Ni]>[CH3:1][N:2]1[CH:10]=[C:9]2[C:4]([C:5]([CH2:12][NH2:13])=[C:6]([CH3:11])[CH:7]=[CH:8]2)=[N:3]1 | 3.5 | CO | null | null | 25 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,167,218 | null | null | null | null | ord_dataset-d24cc23b3db94284bb83a2ccdd9eb880 | 2012-01-01T00:05:00 | true | cis-cis-1,12-Dibromo-dodeca-5,7-diene was added to a solution of 3-picoline (3 mmol) in acetonitrile and the solution refluxed for 24 hours. The acetonitrile was removed in vacuum and the resulting residue was partitioned between ether and water. The aqueous layer was washed extensively with ether until no picoline left in the aqueous layer. The resulting aqueous solution of the product was lyophilized to yield the pure product. (76%). 1HNMR (300 MHz, D2O, ppm) 8.50 (s, 2H), 8.44 (d, J=6.3, 2H), 8.16 (d, J=7.8, 2H), 7.74 (dd, J=7.8, J=6.3, 2H), 6.15-6.18 (m, 2H), 5.38-5.38 (m, 2H), 4.38 (t, J=5.7, 4H), 2.35 (s, 6H), 2.06 (q, J=7.5, 4H), 1.83 (p, J=7.5, 4H), 1.25 (p, J=7.5, 4H). 13CNMR, 145.99, 143.71, 141.30, 139.95, 132.19, 127.46, 124.06, 61.69, 30.27, 26.35, 25.44, 17.93. | Cc1ccc[n+](CCCC/C=C\C=C/CCCC[n+]2cccc(C)c2)c1 | [Br-] | Cc1cccnc1 | BrCCCC/C=C\C=C/CCCCBr | null | [Br:1][CH2:2][CH2:3][CH2:4][CH2:5]/[CH:6]=[CH:7]\[CH:8]=[CH:9]/[CH2:10][CH2:11][CH2:12][CH2:13]Br.[N:15]1[CH:20]=[CH:19][CH:18]=[C:17]([CH3:21])[CH:16]=1>C(#N)C>[Br-:1].[Br-:1].[CH2:2]([N+:15]1[CH:20]=[CH:19][CH:18]=[C:17]([CH3:21])[CH:16]=1)[CH2:3][CH2:4][CH2:5]/[CH:6]=[CH:7]\[CH:8]=[CH:9]/[CH2:10][CH2:11][CH2:12][CH2:13][N+:15]1[CH:20]=[CH:19][CH:18]=[C:17]([CH3:21])[CH:16]=1 | null | CC#N | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
776,665 | null | null | null | null | ord_dataset-bf316bf78f4f45d4b275959c08104b7c | 2007-01-01T00:06:00 | true | A solution of 2-[[bis(allyloxy)phosphoryl]oxymethyl]-3-methylbenzoic acid (880 mg, 2.70 mmol) obtained from Example 22-(5) in dichloromethane (15 ml) was cooled to 0° C., and then N,N-dimethylformamide (15 μl) and oxalyl chloride (1.71 g, 13.5 mmol) were added thereto. After the mixture was stirred at room temperature for 30 minutes, crude 2-[[bis(allyloxy)phosphoryl]oxymethyl]-3-methylbenzoyl chloride was obtained according to a similar procedure to that described in Example 1-(12). | C=CCOP(=O)(OCC=C)OCc1c(C)cccc1C(=O)Cl | null | C=CCOP(=O)(OCC=C)OCc1c(C)cccc1C(=O)O | O=C(Cl)C(=O)Cl | null | [CH2:1]([O:4][P:5]([O:11][CH2:12][C:13]1[C:21]([CH3:22])=[CH:20][CH:19]=[CH:18][C:14]=1[C:15](O)=[O:16])([O:7][CH2:8][CH:9]=[CH2:10])=[O:6])[CH:2]=[CH2:3].CN(C)C=O.C(Cl)(=O)C([Cl:31])=O>ClCCl>[CH2:1]([O:4][P:5]([O:11][CH2:12][C:13]1[C:21]([CH3:22])=[CH:20][CH:19]=[CH:18][C:14]=1[C:15]([Cl:31])=[O:16])([O:7][CH2:8][CH:9]=[CH2:10])=[O:6])[CH:2]=[CH2:3] | 0.5 | CN(C)C=O | ClCCl | null | 25 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
65,115 | null | null | null | null | ord_dataset-d986d6c6630b41ee8d401fd85be47701 | 1980-01-01T00:04:00 | true | A mixture of 2-methyleneglutaric acid [Ber. 34, 427 (1901)] (40 g.) and acetyl chloride (80 ml.) is heated on the steam bath for 1.5 hours. The excess acetyl chloride is removed in vacuo (75°) and the residue is evaporated from toluene twice. Finally, the residue is dissolved in ethanol and heated on the steam bath for one hour. The reaction mixture is concentrated to dryness to yield 2-methylene-4-(ethoxycarbonyl)butyric acid. | C=C(CCC(=O)OCC)C(=O)O | null | C=C(CCC(=O)O)C(=O)O | CC(=O)Cl | null | [CH2:1]=[C:2]([CH2:6][CH2:7][C:8]([OH:10])=[O:9])[C:3]([OH:5])=[O:4].[C:11](Cl)(=O)[CH3:12]>>[CH2:1]=[C:2]([CH2:6][CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])[C:3]([OH:5])=[O:4] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
700,867 | [Na+] | [OH-] | null | null | ord_dataset-bbd7e53f000345838ad4920a07a169ff | 2006-01-01T00:03:00 | true | Ethyl N-(3-cyano-4-neopentyloxyphenyl)-N-[1-(3-trifluoromethylphenyl)-3-methylpyrazol-4-ylcarbonyl]glycine (1.5 g) was added to ethanol (15 ml). 10% Aqueous sodium hydroxide solution (10 ml) was added and the mixture was stirred at a refluxing temperature for 30 min. The solvent was evaporated under reduced pressure. Dilute hydrochloric acid was added to the residue and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, after which the solvent was evaporated under reduced pressure. A mixed solvent of chloroform-n-hexane was added to the residue to allow crystallization. The crystals were recrystallized from hydrous acetic acid to give the title compound (0.9 g), melting point: 110–112° C. | Cc1nn(-c2cccc(C(F)(F)F)c2)cc1C(=O)N(CC(=O)O)c1ccc(OCC(C)(C)C)c(C#N)c1 | null | CCC(C(=O)O)N(C(=O)c1cn(-c2cccc(C(F)(F)F)c2)nc1C)c1ccc(OCC(C)(C)C)c(C#N)c1 | null | null | C([CH:3]([C:37]([OH:39])=[O:38])[N:4]([C:23]1[CH:28]=[CH:27][C:26]([O:29][CH2:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[C:25]([C:35]#[N:36])[CH:24]=1)[C:5]([C:7]1[C:8]([CH3:22])=[N:9][N:10]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=2)[CH:11]=1)=[O:6])C.[OH-].[Na+]>C(O)C>[C:35]([C:25]1[CH:24]=[C:23]([N:4]([C:5]([C:7]2[C:8]([CH3:22])=[N:9][N:10]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:20])([F:21])[F:19])[CH:13]=3)[CH:11]=2)=[O:6])[CH2:3][C:37]([OH:39])=[O:38])[CH:28]=[CH:27][C:26]=1[O:29][CH2:30][C:31]([CH3:34])([CH3:33])[CH3:32])#[N:36] | 0.5 | CCO | null | null | null | null | 63.3 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,393,050 | Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1 | F[P-](F)(F)(F)(F)F | null | null | ord_dataset-12dc3bd21bcf44d09e5b4249afe15161 | 2014-01-01T00:02:00 | true | To a solution of (R)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethanamine (31 mg, 0.07 mmol), prepared as described in Procedure 3, 4, 5 and 6, in DCM (1 mL) was added (9H-fluoren-9-yl)methyl 1-amino-4,4,4-trifluoro-1-oxobutan-2-ylcarbamate (31 mg, 0.08 mmol), followed by PyBrOP and iPr2NEt. The reaction mixture was stirred at rt for 72 h and concentrated. The residue was purified by preparative HPLC (Axia column, 30×100 mm, 60-100% MeOH/H2O with 0.1% TFA over 12 min, flow rate 40 mL/min, monitoring at 220 nm) to yield (9H-fluoren-9-yl)methyl 4,4,4-trifluoro-1-((R)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethylamino)-1-oxobutan-2-ylcarbamate as white solid (20 mg, 38% yield). LCMS: RT=4.5 min [M+H] 787.3 (Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeOH/H2O over 4 minutes containing 0.1% TFA; 4 mL/min, monitoring at 220 nm). This diastereomer mixture was separated by Chiralpak AD column eluting with 10% MeOH/EtOH (1:1)/90% heptane with flow rate 20 mL/min. (9H-fluoren-9-yl)methyl (S)-4,4,4-trifluoro-1-((R)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethylamino)-1-oxobutan-2-ylcarbamate was eluted at a retention time of 8.26 min and isolated as a white solid (10 mg). (9H-fluoren-9-yl)methyl (R)-4,4,4-trifluoro-1-((R)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethylamino)-1-oxobutan-2-ylcarbamate was eluted at a retention time of 12.97 min and isolated as a white solid (10 mg). The stereochemistry of (9H-fluoren-9-yl)methyl (S)-4,4,4-trifluoro-1-((R)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethylamino)-1-oxobutan-2-ylcarbamate and (9H-fluoren-9-yl)methyl (R)-4,4,4-trifluoro-1-((R)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethylamino)-1-oxobutan-2-ylcarbamate was assigned arbitrarily. | O=C(NC(CC(F)(F)F)C(=O)N[C@](Cc1ccccc1)(c1ccc(F)cc1)c1cc(F)cc(OC(F)(F)C(F)F)c1)OCC1c2ccccc2-c2ccccc21 | null | N[C@](Cc1ccccc1)(c1ccc(F)cc1)c1cc(F)cc(OC(F)(F)C(F)F)c1 | NC(=O)C(CC(F)(F)F)NC(=O)OCC1c2ccccc2-c2ccccc21 | null | [F:1][C:2]1[CH:3]=[C:4]([C@@:15]([C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)([NH2:23])[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:5]=[C:6]([O:8][C:9]([F:14])([F:13])[CH:10]([F:12])[F:11])[CH:7]=1.N[C:32](=[O:57])[CH:33]([NH:39][C:40](=[O:56])[O:41][CH2:42][CH:43]1[C:55]2[CH:54]=[CH:53][CH:52]=[CH:51][C:50]=2[C:49]2[C:44]1=[CH:45][CH:46]=[CH:47][CH:48]=2)[CH2:34][C:35]([F:38])([F:37])[F:36].C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[F:36][C:35]([F:37])([F:38])[CH2:34][CH:33]([NH:39][C:40](=[O:56])[O:41][CH2:42][CH:43]1[C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][C:49]=2[C:50]2[C:55]1=[CH:54][CH:53]=[CH:52][CH:51]=2)[C:32]([NH:23][C@@:15]([C:4]1[CH:5]=[C:6]([O:8][C:9]([F:14])([F:13])[CH:10]([F:12])[F:11])[CH:7]=[C:2]([F:1])[CH:3]=1)([C:24]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=1)[CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:57] | 72 | ClCCl | CCN(C(C)C)C(C)C | null | 25 | 36.3 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,221,038 | null | null | null | null | ord_dataset-dc3bb1b1ac4e4229a3fc28fb559a9777 | 2012-01-01T00:10:00 | true | To a stirring solution of 1.00 g (6.77 mmol) of benzofuran-2-ylmethanol in 10 mL of toluene at r.t. was added 1.7 mL (7.89 mmol) of DPPA. The solution was cooled to 0° C. and 1.2 ml (8.02 mmol) of DBU was added. The ice bath was removed, and the mixture was stirred with warming to r.t. After 12.5 h, 1N HCl was added to a pH=4, and the aqueous layer was extracted with EtOAc. The pH of the aqueous layer was then adjusted to pH=6 with saturated NaHCO3 solution, and the aqueous layer was extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SO4, filtered, and concentrated. Purification by flash silica gel chromatography (5% EtOAc/hexanes) provided 2-(azidomethyl)benzofuran as a pale yellow oil in quantitative yield. | [N-]=[N+]=NCc1cc2ccccc2o1 | null | [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1 | OCc1cc2ccccc2o1 | null | [O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[C:2]1[CH2:10]O.C1C=CC(P([N:26]=[N+:27]=[N-:28])(C2C=CC=CC=2)=O)=CC=1.C1CCN2C(=NCCC2)CC1>C1(C)C=CC=CC=1>[N:26]([CH2:10][C:2]1[O:1][C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=1)=[N+:27]=[N-:28] | 12.5 | Cc1ccccc1 | C1CCC2=NCCCN2CC1 | null | 0 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
926,051 | null | null | null | null | ord_dataset-cc0899cd744f4f7f8e7f2463560faad1 | 2009-01-01T00:12:00 | true | To a mixture of 1-(2,6-difluorophenyl)-4-hydroxy-6-methylpyridin-2(1H)-one (0.30 g, 1.26 mmol) in dichloromethane (5 mL) was added NCS (2.52 g, 1.90 mmol). The reaction mixture stirred at room temperature under nitrogen for 4.5 hours. The suspension was cooled in ice bath, filtered, and the solid was rinsed with fresh dichloromethane to afford the desired product (0.271 g, 79%) as a white solid. 1H-NMR (CD3OD, 400 MHz) δ 7.58 (m, 1H), 7.22 (m, 2H), 6.20 (s 1H), 2.00 (s, 3H); ES-HRMS m/z 272.0287 (M+H calculated for C12H9NO2F2Cl requires 272.0290). | Cc1cc(O)c(Cl)c(=O)n1-c1c(F)cccc1F | null | Cc1cc(O)cc(=O)n1-c1c(F)cccc1F | O=C1CCC(=O)N1Cl | null | [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[N:9]1[C:14]([CH3:15])=[CH:13][C:12]([OH:16])=[CH:11][C:10]1=[O:17].C1C(=O)N([Cl:25])C(=O)C1>ClCCl>[Cl:25][C:11]1[C:10](=[O:17])[N:9]([C:3]2[C:4]([F:8])=[CH:5][CH:6]=[CH:7][C:2]=2[F:1])[C:14]([CH3:15])=[CH:13][C:12]=1[OH:16] | 4.5 | ClCCl | null | null | 25 | null | 79.2 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,568,172 | [H-] | [Na+] | null | null | ord_dataset-9741bb5fd93044078df2a45f45733054 | 2015-01-01T00:04:00 | true | A mixture of compound 2,3,4,5-tetrahydro-2,8-dimethyl-1H-pyrido[4,3-b]indole (2.6 g, 13.1 mmol, 1 equiv.) and NaH (55%, 750 mg, 17.2 mmol, 1.3 equiv.) in 60 ml of THF was heated to 120 deg C. for 1 h. It was then cooled to RT and compound 2-(4-fluorophenyl)-2-methyloxirane (4 g, 26 mmol, 2 equiv.) in 25 ml of DMF was added dropwise for 5 mins at RT followed by heating at 120 deg C. for 2 h. It was cooled to RT and 10 ml of water was added followed by dilution with 800 ml of ethyl acetate, which was first washed with water (150 ml×3) and then brine, dried over sodium sulphate and concentrated under vacuum. Column purified over 230-400 Silica gel (flash) using 15% methanol in ethyl acetate as eluent, Yield: 3 g (66%). | Cc1ccc2c(c1)c1c(n2C(c2ccc(F)cc2)C(C)O)CCN(C)C1 | null | CC1(c2ccc(F)cc2)CO1 | Cc1ccc2[nH]c3c(c2c1)CN(C)CC3 | C1CCOC1 | [CH3:1][N:2]1[CH2:15][CH2:14][C:5]2[NH:6][C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1.[H-].[Na+].[F:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2(C)[CH2:27][O:26]2)=[CH:21][CH:20]=1.O.[CH2:30]1COCC1>CN(C=O)C.C(OCC)(=O)C>[F:18][C:19]1[CH:20]=[CH:21][C:22]([CH:25]([N:6]2[C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]3[CH2:3][N:2]([CH3:1])[CH2:15][CH2:14][C:5]2=3)[CH:27]([OH:26])[CH3:30])=[CH:23][CH:24]=1 | 1 | O | CCOC(C)=O | CN(C)C=O | 25 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,349,741 | null | null | null | null | ord_dataset-6034127657614f02860ed057b62b882e | 2013-01-01T00:10:00 | true | To a stirred solution of 6.16 g (30.2 mmol) 2c and 110 ml dichloromethane were added 50.0 g (302 mmol) methyltriflate (Aldrich) drop wisely. The reaction mixture was stirred over night and diethylether was added. After evaporation of one third of the solvent volume the desired compound precipitates and the rest of the solvent was decanted. The solid was washed extensively (ten times) with large amounts of diethylether. The solid was dried by use of oil pump vacuum and purified by (C-18) RP-column chromatography (acetonitril/water-gradient 1:99 to 80:20). The desired compound 2d was obtained in 69% yield (20.8 mmol, 7.68 g). | COC(=O)c1ccc([N+](C)(C)C)c(C#N)c1 | O=S(=O)([O-])C(F)(F)F | ClCCl | COS(=O)(=O)C(F)(F)F | COC(=O)c1ccc(N(C)C)c(C#N)c1 | [CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:9]=[CH:8][C:7]([N:10]([CH3:12])[CH3:11])=[C:6]([C:13]#[N:14])[CH:5]=1.Cl[CH2:17]Cl.C[O:20][S:21]([C:24]([F:27])([F:26])[F:25])(=[O:23])=[O:22]>C(OCC)C>[F:25][C:24]([F:27])([F:26])[S:21]([O-:23])(=[O:22])=[O:20].[C:13]([C:6]1[CH:5]=[C:4]([C:3]([O:2][CH3:1])=[O:15])[CH:9]=[CH:8][C:7]=1[N+:10]([CH3:17])([CH3:11])[CH3:12])#[N:14] | null | CCOCC | null | null | null | null | 69 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,246,842 | Cl | null | null | null | ord_dataset-c544c0c663f54dbea4ddb52ddde7934e | 2013-01-01T00:01:00 | true | By reaction and treatment in the same manner as in Example 49 and using (S)-4-(4-isopropyl-2-oxooxazolidin-3-yl)benzoic acid (496 mg) described in Preparation Example 80 and 1-(3,5-dimethylpyridin-2-yl)piperazine hydrochloride (455 mg) described in Preparation Example 64, the title compound (583 mg) was obtained. | Cc1cnc(N2CCN(C(=O)c3ccc(N4C(=O)OC[C@@H]4C(C)C)cc3)CC2)c(C)c1 | null | CC(C)[C@H]1COC(=O)N1c1ccc(C(=O)O)cc1 | Cc1cnc(N2CCNCC2)c(C)c1 | null | [CH:1]([C@H:4]1[CH2:8][O:7][C:6](=[O:9])[N:5]1[C:10]1[CH:18]=[CH:17][C:13]([C:14]([OH:16])=O)=[CH:12][CH:11]=1)([CH3:3])[CH3:2].Cl.[CH3:20][C:21]1[C:22]([N:28]2[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)=[N:23][CH:24]=[C:25]([CH3:27])[CH:26]=1>>[CH3:20][C:21]1[C:22]([N:28]2[CH2:29][CH2:30][N:31]([C:14]([C:13]3[CH:12]=[CH:11][C:10]([N:5]4[C@@H:4]([CH:1]([CH3:2])[CH3:3])[CH2:8][O:7][C:6]4=[O:9])=[CH:18][CH:17]=3)=[O:16])[CH2:32][CH2:33]2)=[N:23][CH:24]=[C:25]([CH3:27])[CH:26]=1 | null | null | null | null | null | null | 69.3 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,458,914 | CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21 | null | null | null | ord_dataset-a86112d52cd54525a5e36d41f18aced2 | 2014-01-01T00:07:00 | true | To a solution of [9-chloro-1-(6-methoxy-2-methylpyridin-3-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]methanol (4.00 g, 11.15 mmol) in dimethylsulfoxide (70.0 mL) was added Dess-Martin reagent (5.20 g, 12.26 mmol). The mixture was stirred at room temperature for 3 hrs. The mixture was quenched with aqueous saturated sodium hydrogen carbonate and aqueous saturated sodium thiosulfate and extracted with ethyl acetate (×3). The combined organic layer was washed with water (×2) and brine (×1), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The resulting solid was washed with ethyl acetate/diisopropyl ether to give the title compound as a pale yellow solid (3.69 g, 10.34 mmol, 93%). | COc1ccc(N2CCCn3c2nc2c(Cl)ccc(C=O)c23)c(C)n1 | null | COc1ccc(N2CCCn3c2nc2c(Cl)ccc(CO)c23)c(C)n1 | null | null | [Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:15]4[C:16]([CH3:23])=[N:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=4)[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([CH2:24][OH:25])=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>CS(C)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:24]=[O:25])=[C:6]2[C:10]=1[N:9]=[C:8]1[N:11]([C:15]3[C:16]([CH3:23])=[N:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=3)[CH2:12][CH2:13][CH2:14][N:7]21 | 3 | CS(C)=O | null | null | 25 | null | 92.7 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,334,315 | CCOC(=O)N=NC(=O)OCC | c1ccc(P(c2ccccc2)c2ccccc2)cc1 | null | null | ord_dataset-08852243bba44cb28769a5833f1515fe | 2013-01-01T00:09:00 | true | To a mixture of 0.81 g of 4-hydroxy-3-[3-(3-methylphenyl)-1-oxo-2-propenyl]-6-methyl-2H-pyran-2-one, 10 ml of tetrahydrofuran, 0.25 ml of 2-methoxyethanol, and 0.87 g of triphenylphosphine was added dropwise a solution of 0.57 g of diethyl azodicarboxylate in 6 ml of tetrahydrofuran, and this was stirred at room temperature overnight. The solvent was distilled off under reduced pressure, and the resulting residue was subjected to silica gel column chromatography to obtain 389 mg of 4-(2-methoxyethoxy)-3-[3-(3-methylphenyl)-1-oxo-2-propenyl]-6-methyl-2H-pyran-2-one [Compound No. (2a-24)] as a yellow oil. | COCCOc1cc(C)oc(=O)c1C(=O)C=Cc1cccc(C)c1 | null | COCCO | Cc1cccc(C=CC(=O)c2c(O)cc(C)oc2=O)c1 | null | [OH:1][C:2]1[CH:7]=[C:6]([CH3:8])[O:5][C:4](=[O:9])[C:3]=1[C:10](=[O:20])[CH:11]=[CH:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([CH3:19])[CH:14]=1.[CH3:21][O:22][CH2:23][CH2:24]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[CH3:21][O:22][CH2:23][CH2:24][O:1][C:2]1[CH:7]=[C:6]([CH3:8])[O:5][C:4](=[O:9])[C:3]=1[C:10](=[O:20])[CH:11]=[CH:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([CH3:19])[CH:14]=1 | 8 | C1CCOC1 | null | null | 25 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,761,688 | Cl | null | null | null | ord_dataset-97eb2ab57fec4160922caae33b54d956 | 2016-01-01T00:08:00 | true | 4 M HCl in 1,4-dioxane (6 mL, 24 mmol) was added to a solution of 1-benzyl 4-tert-butyl 2-(2-(pyridin-3-yl)ethyl)piperazine-1,4-dicarboxylate (130.2 mg, 0.306 mmol) in MeOH (1 mL). After 1 h, the reaction mixture was concentrated under reduced pressure and purified by HPLC (5 to 50% MeCN/0.1% TFA in H2O/0.1% TFA gradient). The fractions containing the desired product were concentrated under reduced pressure. The material was dissolved in MeOH (1 mL) and 4 M HCl in 1,4-dioxane (0.015 mL) was added. The mixture was concentrated under reduced pressure to give 71.0 mg (58%) of the desired product. LC-MS: RT=3.50 min, [M+H]+=326.2. | O=C(OCc1ccccc1)N1CCNCC1CCc1cccnc1 | null | CC(C)(C)OC(=O)N1CCN(C(=O)OCc2ccccc2)C(CCc2cccnc2)C1 | null | null | [ClH:1].O1CCOCC1.[N:8]1[CH:13]=[CH:12][CH:11]=[C:10]([CH2:14][CH2:15][CH:16]2[CH2:21][N:20](C(OC(C)(C)C)=O)[CH2:19][CH2:18][N:17]2[C:29]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[O:30])[CH:9]=1>CO>[ClH:1].[ClH:1].[N:8]1[CH:13]=[CH:12][CH:11]=[C:10]([CH2:14][CH2:15][CH:16]2[CH2:21][NH:20][CH2:19][CH2:18][N:17]2[C:29]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[O:30])[CH:9]=1 | 1 | CO | C1COCCO1 | null | null | 58 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,703,551 | [Pd] | null | null | null | ord_dataset-54347fcace774f89850681d6dec8009f | 2016-01-01T00:03:00 | true | A suspension of 5,6-bis(benzyloxy)-N-(cyclopropylmethyl)-N-methylpyridazin-3-amine (Intermediate 46; 2.44 mmol) and palladium on carbon (10% wt loading, dry basis; 0.259 g, 0.244 mmol) in ethyl acetate (10 ml) was stirred under a hydrogen atmosphere for 2 hours. The reaction mixture was filtered through a diatomaceous earth cartridge commercially sold under the trade mark ‘Celite’, eluting with ethyl acetate, tetrahydrofuran and methanol. The filtrate was concentrated in vacuo to afford a brown solid, which was triturated from ethyl acetate to give the title compound as a pale brown solid (27.9 mg, 38%). | CN(CC1CC1)c1cc(O)c(=O)[nH]n1 | null | CN(CC1CC1)c1cc(OCc2ccccc2)c(OCc2ccccc2)nn1 | null | null | C([O:8][C:9]1[CH:10]=[C:11]([N:23]([CH2:25][CH:26]2[CH2:28][CH2:27]2)[CH3:24])[N:12]=[N:13][C:14]=1[O:15]CC1C=CC=CC=1)C1C=CC=CC=1>[Pd].C(OCC)(=O)C>[CH:26]1([CH2:25][N:23]([CH3:24])[C:11]2[CH:10]=[C:9]([OH:8])[C:14](=[O:15])[NH:13][N:12]=2)[CH2:27][CH2:28]1 | 2 | CCOC(C)=O | null | null | null | null | 5.9 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,642,822 | Cl | [Na+] | [OH-] | null | ord_dataset-bcc0b01d4f58457a8733b10a099f43ba | 2015-01-01T00:10:00 | true | Water (2 ml) and 4N aqueous solution of sodium hydroxide (2 ml) were added to a solution of 1-(3-chloro-5-cyclopropylpyridin-2-yl)-5-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (240 mg) in ethanol (4 ml) at room temperature, and stirred at 90° C. for six hours. After completion of the reaction, the reaction solution was cooled to 0° C. and 1N hydrochloric acid aqueous solution (9 ml) was added. The precipitated solid was collected by filtration to give the titled compound (157 mg) as a light brown solid. | Cc1c(C(=O)O)cnn1-c1ncc(C2CC2)cc1Cl | null | CCOC(=O)c1cnn(-c2ncc(C3CC3)cc2Cl)c1C | null | null | O.[OH-].[Na+].C([O:6][C:7]([C:9]1[CH:10]=[N:11][N:12]([C:15]2[C:20]([Cl:21])=[CH:19][C:18]([CH:22]3[CH2:24][CH2:23]3)=[CH:17][N:16]=2)[C:13]=1[CH3:14])=[O:8])C.Cl>C(O)C>[Cl:21][C:20]1[C:15]([N:12]2[C:13]([CH3:14])=[C:9]([C:7]([OH:8])=[O:6])[CH:10]=[N:11]2)=[N:16][CH:17]=[C:18]([CH:22]2[CH2:23][CH2:24]2)[CH:19]=1 | 6 | CCO | O | null | 90 | null | 72 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,540,923 | Cl | null | null | null | ord_dataset-cac8df8aff894288876df4e093c9877f | 2015-01-01T00:02:00 | true | In 4 mL of dioxane, tert-butyl (1-(3,5-difluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methylcarbamate (214 mg, 0.567 mmol, 1 equiv.) was dissolved and hydrogen chloride in dioxane (0.923 mL, c=4 mol/L, 3.69 mmo, 6.5 equiv.) was added. The reaction mixture was stirred overnight at room temperature, the precipitate was filtered out, washed with dioxane (2×15 mL) and dried to give (1-(3,5-difluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methanamine hydrochloride (139 mg, 78%). | NCc1cc(C(F)(F)F)nn1-c1cc(F)cc(F)c1 | null | CC(C)(C)OC(=O)NCc1cc(C(F)(F)F)nn1-c1cc(F)cc(F)c1 | null | null | [F:1][C:2]1[CH:3]=[C:4]([N:9]2[C:13]([CH2:14][NH:15]C(=O)OC(C)(C)C)=[CH:12][C:11]([C:23]([F:26])([F:25])[F:24])=[N:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1.[ClH:27]>O1CCOCC1>[ClH:27].[F:1][C:2]1[CH:3]=[C:4]([N:9]2[C:13]([CH2:14][NH2:15])=[CH:12][C:11]([C:23]([F:25])([F:24])[F:26])=[N:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1 | 8 | C1COCCO1 | null | null | 25 | 78 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
925,357 | C[O-] | [Na+] | null | null | ord_dataset-cc0899cd744f4f7f8e7f2463560faad1 | 2009-01-01T00:12:00 | true | A mixture of 113 mg of 4-hydroxy-7-phenylsulfanyl-isoquinoline-3-carboxylic acid butyl ester (0.32 mmol), 244 mg of glycine (3.2 mmol), and 6.4 ml of a 0.5 N solution of sodium methoxide in methanol (3.2 mmol) was refluxed for 24 h with stirring. Then the solvent was evaporated in vacuo, the residue dissolved in 25 ml of water and the resulting solution was washed twice with 50 ml of ethyl acetate. The pH of the solution was subsequently adjusted to about 3 by addition of concentrated hydrochloric acid and the resulting slurry was extracted twice with 25 ml of ethyl acetate. The combined extracts were dried over MgSO4 and evaporated in vacuo. 103 mg of the title compound were obtained; 1H NMR (DMSO-d6): δ=9.32 (t, 1H), 8.74 (s, 1H), 8.19 (d, 1H), 7.94 (d, 1H), 7.45 to 7.65 (m, 6H), 4.02 (d, 2H). | O=C(O)CNC(=O)c1ncc2cc(Sc3ccccc3)ccc2c1O | null | NCC(=O)O | CCCCOC(=O)c1ncc2cc(Sc3ccccc3)ccc2c1O | null | C(O[C:6]([C:8]1[N:9]=[CH:10][C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][CH:14]=[C:13]([S:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH:12]=2)=[O:7])CCC.[NH2:26][CH2:27][C:28]([OH:30])=[O:29].C[O-].[Na+].CO>>[OH:18][C:17]1[C:16]2[C:11](=[CH:12][C:13]([S:19][C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)=[CH:14][CH:15]=2)[CH:10]=[N:9][C:8]=1[C:6]([NH:26][CH2:27][C:28]([OH:30])=[O:29])=[O:7] | null | CO | null | null | null | null | 90.8 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,651,192 | null | null | null | null | ord_dataset-42cd9bc5aae3485f9a58f1527bd3abf0 | 2015-01-01T00:11:00 | true | The title compound was synthesized from 1-bromo-4-hydroxy-6-(2,4,6-trimethyl-phenoxy)-isoquinoline-3-carboxylic acid butyl ester and CuCN in analogy to example 3a; MS-(−)-ion: M−1=403.4. | CCCCOC(=O)c1nc(C#N)c2ccc(Oc3c(C)cc(C)cc3C)cc2c1O | null | N#C[Cu] | CCCCOC(=O)c1nc(Br)c2ccc(Oc3c(C)cc(C)cc3C)cc2c1O | null | [CH2:1]([O:5][C:6]([C:8]1[N:9]=[C:10](Br)[C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][C:14]([O:19][C:20]1[C:25]([CH3:26])=[CH:24][C:23]([CH3:27])=[CH:22][C:21]=1[CH3:28])=[CH:13][CH:12]=2)=[O:7])[CH2:2][CH2:3][CH3:4].[C:30]([Cu])#[N:31]>>[CH2:1]([O:5][C:6]([C:8]1[N:9]=[C:10]([C:30]#[N:31])[C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][C:14]([O:19][C:20]1[C:25]([CH3:26])=[CH:24][C:23]([CH3:27])=[CH:22][C:21]=1[CH3:28])=[CH:13][CH:12]=2)=[O:7])[CH2:2][CH2:3][CH3:4] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,480,741 | Cl | null | null | null | ord_dataset-c3c1091f873b4f40827973a6f1f9b685 | 2014-01-01T00:09:00 | true | 15.5 g (43.9 mmol) 1-benzyl-4-(2-chloro-quinolin-3-yl)-piperidin-4-ol were refluxed for 8 h in 150 mL of a 6M aqueous hydrochloric acid solution. 100 mL water were added dropwise to the reaction mixture and the precipitated solid was suction filtered, dried and then stirred into 150 mL of a 15%, aqueous potassium carbonate solution. After the precipitate had been suction filtered the product was obtained as a free base and dried. | Oc1nc2ccccc2cc1C1=CCN(Cc2ccccc2)CC1 | null | OC1(c2cc3ccccc3nc2Cl)CCN(Cc2ccccc2)CC1 | O | null | [CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([C:15]2[C:16](Cl)=[N:17][C:18]3[C:23]([CH:24]=2)=[CH:22][CH:21]=[CH:20][CH:19]=3)(O)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[OH2:27]>>[CH2:1]([N:8]1[CH2:13][CH:12]=[C:11]([C:15]2[C:16]([OH:27])=[N:17][C:18]3[C:23]([CH:24]=2)=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
550,148 | null | null | null | null | ord_dataset-e967d076b4894c2c854795f019ed3c39 | 2002-01-01T00:06:00 | true | To a mixture of 1-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-tetrazol-1-yl)phenyl]-2-imidazolidinone (0.80 g) and chloromethyl propanate (4.07 g) was added acetonitrile (1.6 ml), and the mixture was stirred for 10 hours at 100° C. under an argon atmosphere. The reaction mixture was concentrated under reduced pressure, and to the residue was added diisopropyl ether (8 ml). The resulting powder was collected by filtration. The powder was subjected to silica gel flush chromatography (eluent: ethyl acetate→acetone→acetone/ethanol=9/1→5/1), and the fraction containing the desired compound was concentrated under reduced pressure. The residue was subjected to ODS column chromatography (eluent: methanol/water=3/2). The eluate was concentrated in vacuo, and the residue was dissolved in water (10 ml). The solution was lyophilized to give 1-[(2R,3R)-2-(2,4-difluorophenyl)-2-hydroxy-3-[2-oxo-3-[4-(1H-tetrazol-1-yl)phenyl]-1-imidazolidinyl]butyl]-4-propanoyloxymethyl-1H-1,2,4-triazolium chloride (Compound 14, 0.04 g) as a white powder. | CCC(=O)OCN1C=N[NH+](C[C@](O)(c2ccc(F)cc2F)[C@@H](C)N2CCN(c3ccc(-n4cnnn4)cc3)C2=O)C1 | [Cl-] | C[C@@H](N1CCN(c2ccc(-n3cnnn3)cc2)C1=O)[C@](O)(Cn1cncn1)c1ccc(F)cc1F | CCC(=O)OCCl | null | [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@:9]([OH:35])([CH2:29][N:30]1[CH:34]=[N:33][CH:32]=[N:31]1)[C@H:10]([N:12]1[CH2:16][CH2:15][N:14]([C:17]2[CH:22]=[CH:21][C:20]([N:23]3[CH:27]=[N:26][N:25]=[N:24]3)=[CH:19][CH:18]=2)[C:13]1=[O:28])[CH3:11].[C:36]([O:40][CH2:41][Cl:42])(=[O:39])[CH2:37][CH3:38]>C(#N)C>[Cl-:42].[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@:9]([OH:35])([C@H:10]([N:12]1[CH2:16][CH2:15][N:14]([C:17]2[CH:22]=[CH:21][C:20]([N:23]3[CH:27]=[N:26][N:25]=[N:24]3)=[CH:19][CH:18]=2)[C:13]1=[O:28])[CH3:11])[CH2:29][NH+:30]1[CH2:34][N:33]([CH2:41][O:40][C:36](=[O:39])[CH2:37][CH3:38])[CH:32]=[N:31]1 | 10 | CC#N | null | null | 100 | null | 4 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,411,409 | null | null | null | null | ord_dataset-7456bda2326f4bebaa874a5474d4cc0d | 2014-01-01T00:03:00 | true | Triethylamine (5 ml, 35.9 mmol) is added, dropwise, to a solution of 4-(4-benzyloxy-2,6-dimethylphenyl)-10-oxatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione (5.0 g, 13.4 mmol) and trimethylacetyl chloride (5 ml, 40.6 mmol) in dry dichloromethane (75 ml). The mixture is stirred for 2 hours at room temperature, then silica gel is added and the solvent is evaporated under reduced pressure. The residue is purified by column chromatography on silica gel to give rac-(1R,2S,6R,7S)-4-(4-benzyloxy-2,6-dimethylphenyl)-5-oxo-10-oxatricyclo[5.2.1.02,6]deca-3,8-dien-3-yl 2,2-dimethylpropionate. | Cc1cc(OCc2ccccc2)cc(C)c1C1=C(OC(=O)C(C)(C)C)C2C3C=CC(O3)C2C1=O | null | Cc1cc(OCc2ccccc2)cc(C)c1C1C(=O)C2C3C=CC(O3)C2C1=O | CC(C)(C)C(=O)Cl | null | C(N(CC)CC)C.[CH2:8]([O:15][C:16]1[CH:21]=[C:20]([CH3:22])[C:19]([CH:23]2[C:31](=[O:32])[CH:30]3[CH:25]([CH:26]4[O:33][CH:29]3[CH:28]=[CH:27]4)[C:24]2=[O:34])=[C:18]([CH3:35])[CH:17]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[CH3:36][C:37]([CH3:42])([CH3:41])[C:38](Cl)=[O:39]>ClCCl>[CH3:36][C:37]([CH3:42])([CH3:41])[C:38]([O:32][C:31]1[CH:30]2[CH:25]([C:24](=[O:34])[C:23]=1[C:19]1[C:18]([CH3:35])=[CH:17][C:16]([O:15][CH2:8][C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)=[CH:21][C:20]=1[CH3:22])[CH:26]1[O:33][CH:29]2[CH:28]=[CH:27]1)=[O:39] | 2 | ClCCl | CCN(CC)CC | null | 25 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
1,051,845 | O=C([O-])C(F)(F)F | null | null | null | ord_dataset-373415d3e0e54004837cf4831e67666f | 2011-01-01T00:05:00 | true | The title compound was prepared from 3-(1-benzyl-1H-[1,2,4]triazol-3-yl)-2-[cyclopropyl-(4-trifluoromethoxy-benzoyl)-amino]-3-oxo-propionic acid ethyl ester in direct analogy to intermediate 8B, by reaction with ammonium trifluoroacetate. MS: 498.2 (MH+). | CCOC(=O)c1c(-c2ncn(Cc3ccccc3)n2)nc(-c2ccc(OC(F)(F)F)cc2)n1C1CC1 | null | [NH4+] | CCOC(=O)C(C(=O)c1ncn(Cc2ccccc2)n1)N(C(=O)c1ccc(OC(F)(F)F)cc1)C1CC1 | null | [CH2:1]([O:3][C:4](=[O:37])[CH:5]([N:20]([CH:34]1[CH2:36][CH2:35]1)[C:21](=O)[C:22]1[CH:27]=[CH:26][C:25]([O:28][C:29]([F:32])([F:31])[F:30])=[CH:24][CH:23]=1)[C:6]([C:8]1[N:12]=[CH:11][N:10]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:9]=1)=O)[CH3:2].FC(F)(F)C([O-])=O.[NH4+:45]>>[CH2:1]([O:3][C:4]([C:5]1[N:20]([CH:34]2[CH2:35][CH2:36]2)[C:21]([C:22]2[CH:27]=[CH:26][C:25]([O:28][C:29]([F:31])([F:32])[F:30])=[CH:24][CH:23]=2)=[N:45][C:6]=1[C:8]1[N:12]=[CH:11][N:10]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:9]=1)=[O:37])[CH3:2] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
941,601 | null | null | null | null | ord_dataset-ed680843f6d14f5c9901869b2a06b4a4 | 2010-01-01T00:03:00 | true | To a solution of Example 17D (32 mg, 0.1 mmol) in anhydrous THF (5 mL) was added N,N-diisopropylethylamine (0.035 mL, 0.2 mmol), followed by phenyl chloroformate (17.22 mg, 0.11 mmol). The mixture was stirred for 8 hours at room temperature and concentrated under reduced pressure. The residue was taken up in anhydrous dichloromethane (3 mL) and trifluoracetic acid (0.075 mL) in dichloromethane (0.075 mL) were added. The mixture was stirred for 5 hours at room temperature, concentrated under reduced pressure and purified using RP-HPLC to provide the titled compound. MS (ESI) m/e 336 (M+H)+; 1H NMR (400 MHz, CD3OD) δ ppm 1.77 (m, 1 H) 2.69 (m, 2 H) 3.07 (m, 1 H) 3.17 (m, 2 H) 3.25 (m, 1 H) 3.52 (m, 2 H) 3.75 (m, 1 H) 3.88 (m, 1 H) 4.52 (m, 1 H) 4.66 (m, 2 H) 7.10 (d, 2 H) 7.21 (t, 1 H) 7.37 (t, 2 H). | O=C(NC[C@@H]1CN[C@H](C(=O)N2CCSC2)C1)Oc1ccccc1 | null | CC(C)(C)OC(=O)N1C[C@@H](CN)C[C@H]1C(=O)N1CCSC1 | O=C(Cl)Oc1ccccc1 | null | C(OC([N:8]1[CH2:12][C@@H:11]([CH2:13][NH2:14])[CH2:10][C@H:9]1[C:15]([N:17]1[CH2:21][CH2:20][S:19][CH2:18]1)=[O:16])=O)(C)(C)C.C(N(CC)C(C)C)(C)C.Cl[C:32]([O:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[O:33]>C1COCC1>[C:35]1([O:34][C:32](=[O:33])[NH:14][CH2:13][C@H:11]2[CH2:10][C@@H:9]([C:15]([N:17]3[CH2:21][CH2:20][S:19][CH2:18]3)=[O:16])[NH:8][CH2:12]2)[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1 | 8 | CCN(C(C)C)C(C)C | C1CCOC1 | null | 25 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
249,634 | null | null | null | null | ord_dataset-4f3b2ca6df1d41ef8b5008f1f39da0e2 | 1992-01-01T00:06:00 | true | Mon-ethyl methoxy(methyl)malonate (14.52 grams, 0.08 mole) was reacted with thionyl chloride (19.61 grams, 0.16 mole) at 50° C. for a 13-hour reaction period with an additional holding period of approximately 32 hours at room temperature. Vacuum evaporation of the excess thionyl chloride gave 15.2 grams (0.08 mole) of ethyl 2-(chlorocarbonyl)-2-methoxypropionate. NMR analysis of the product indicated the following: | CCOC(=O)C(C)(OC)C(=O)Cl | null | CCOC(=O)C(C)(OC)C(=O)[O-] | O=S(Cl)Cl | null | [CH3:1][O:2][C:3]([CH3:12])([C:9]([O-])=[O:10])[C:4]([O:6][CH2:7][CH3:8])=[O:5].S(Cl)([Cl:15])=O>>[Cl:15][C:9]([C:3]([O:2][CH3:1])([CH3:12])[C:4]([O:6][CH2:7][CH3:8])=[O:5])=[O:10] | null | null | null | null | null | null | 100 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null |
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