original_index int64 2 1.77M | extracted_from_file stringclasses 489 values | date_of_experiment timestamp[ns]date | grant_date timestamp[ns]date 1976-01-01 00:01:00 2016-01-01 00:09:00 | is_mapped bool 1 class | rxn_str stringlengths 87 6.12k | reactant_000 stringlengths 1 902 | reactant_001 stringlengths 1 902 ⌀ | reactant_002 null | agent_000 stringlengths 1 540 ⌀ | agent_001 stringlengths 1 852 ⌀ | agent_002 stringlengths 1 247 ⌀ | agent_003 null | agent_004 null | agent_005 null | agent_006 null | agent_007 null | agent_008 null | agent_009 null | agent_010 null | agent_011 null | agent_012 null | agent_013 null | agent_014 null | agent_015 null | agent_016 null | solvent_000 stringclasses 446 values | solvent_001 stringclasses 405 values | solvent_002 null | solvent_003 null | solvent_004 null | solvent_005 null | solvent_006 null | solvent_007 null | solvent_008 null | solvent_009 null | solvent_010 null | temperature float64 -230 30.1k ⌀ | rxn_time float64 0 2.16k ⌀ | procedure_details stringlengths 8 24.5k | product_000 stringlengths 1 484 | product_001 null | yield_000 float64 0 90,205,156,600B ⌀ | yield_001 float64 0 100M ⌀ |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
921,076 | ord_dataset-8e59bd24817446f7b1c68e805b8e5f1d | null | 2009-01-01T00:11:00 | true | [O:1]=[C:2]([NH:8][CH2:9][C:10]1[N:15]=[CH:14][CH:13]=[CH:12][N:11]=1)[C:3]([O:5][CH2:6][CH3:7])=[O:4].I[CH3:17].[H-].[Na+]>CN(C=O)C>[O:1]=[C:2]([N:8]([CH3:17])[CH2:9][C:10]1[N:11]=[CH:12][CH:13]=[CH:14][N:15]=1)[C:3]([O:5][CH2:6][CH3:7])=[O:4] | CCOC(=O)C(=O)NCc1ncccn1 | CI | null | [H-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | 25 | 18 | A solution ethyl 2-oxo-2-[(pyrimidin-2-yl)methylamino]acetate from the previous step (1.0 g, 4.8 mmol) and iodomethane (0.5 mL, 8 mmol) in DMF (15 mL) was cooled to 0° C. and NaH (0.23 g of a 60% dispersion in mineral oil, 5.7 mmol) was added. The cooling bath was removed and the mixture was stirred at ambient temperature for 18 hours. Ethanol was added to quench the reaction and the solvent was removed under reduced pressure. The residue was purified by pressurized silica gel column chromatography using a gradient of 80-100% EtOAc in hexanes. The solvent was removed under reduced pressure from the fractions containing product to give the title compound as an oil. 1H NMR (400 MHz, DMSO-d6) δ 8.81 (m, 2H), 7.45 (m, 1H), 4.74 (m, 2H), 4.32, 4.13 (two q, rotamers, J=7 Hz, 2H), 3.08, 3.00 (two s, rotamers, 3H), 1.30, 1.08 (two t, rotamers, 3H); ES MS M+1=224. | CCOC(=O)C(=O)N(C)Cc1ncccn1 | null | null | null |
949,302 | ord_dataset-3feb2a95f66e4706a4a50c977ccd9bf8 | null | 2010-01-01T00:04:00 | true | [Cl:1][C:2]1[CH:13]=[C:12]([Cl:14])[C:5]([C:6]([NH:8][CH:9]2[CH2:11][CH2:10]2)=[O:7])=[C:4]([N+:15]([O-])=O)[C:3]=1[OH:18].O.[Sn](Cl)Cl>>[NH2:15][C:4]1[C:3]([OH:18])=[C:2]([Cl:1])[CH:13]=[C:12]([Cl:14])[C:5]=1[C:6]([NH:8][CH:9]1[CH2:11][CH2:10]1)=[O:7] | O=C(NC1CC1)c1c(Cl)cc(Cl)c(O)c1[N+](=O)[O-] | null | null | Cl[Sn]Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | null | null | null | null | null | null | null | null | null | null | null | null | Reduction of 4,6-dichloro-N-cyclopropyl-3-hydroxy-2-nitrobenzamide with tin (II) chloride hydrate using the conditions as described in Step B yielded 2-amino-4,6-dichloro-N-cyclopropyl-3-hydroxybenzamide (93%).—1H NMR (CD3OD): δ 6.67 (s, 1H), 2.86 (m, 1H), 0.79 (m, 2H), 0.62 (m, 2H). | Nc1c(O)c(Cl)cc(Cl)c1C(=O)NC1CC1 | null | 93 | null |
1,536,451 | ord_dataset-8d5c200bca27407ab9febe7598e16458 | null | 2015-01-01T00:01:00 | true | [CH2:1]([O:3][C:4]1[C:9]([I:10])=[CH:8][N:7]=[C:6]([OH:11])[CH:5]=1)[CH3:2].Br[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>C1COCC1.C(=O)([O-])[O-].[Ag+2]>[CH2:13]([O:11][C:6]1[CH:5]=[C:4]([O:3][CH2:1][CH3:2])[C:9]([I:10])=[CH:8][N:7]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1 | BrCc1ccccc1 | CCOc1cc(O)ncc1I | null | [Ag+2] | O=C([O-])[O-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | 70 | 16 | To a mixture of 4-ethoxy-5-iodopyridin-2-ol (800 mg, 3.02 mmol) in THF (10 mL) was added (bromomethyl)benzene (619 mg, 3.62 mmol) and silver carbonate (1665 mg, 6.04 mmol). The mixture was stirred at 70° C. for 16 h. The reaction residue was filtered and the filtrate was concentrated. The mixture was diluted with H2O and extracted with DCM. The combined organic extract was washed with brine, dried over MgSO4, filtered and concentrated. The resulting 2-(benzyloxy)-4-ethoxy-5-iodopyridine (800 mg, 1.915 mmol, 63.4% yield) was used to next step without further purification: 1H NMR (400 MHz, CDCl3) δ 8.28 (s, 1H), 7.45-7.43 (m, 2H), 7.38-7.36 (m, 3H), 6.22 (s, 1H), 5.33 (s, 2H), 4.12-4.07 (m, 2H), 1.48 (t, J=6.8 Hz, 3H); ES-LCMS m/z 355.9 (M+H). | CCOc1cc(OCc2ccccc2)ncc1I | null | 63.4 | null |
916,613 | ord_dataset-8e59bd24817446f7b1c68e805b8e5f1d | null | 2009-01-01T00:11:00 | true | C(OC([N:11]1[CH2:16][CH2:15][CH:14]([C:17]2[NH:18][C:19]([C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([CH3:37])[N:32]=3)=[C:20]([C:22]3[CH:30]=[CH:29][C:25]4[O:26][CH2:27][O:28][C:24]=4[CH:23]=3)[N:21]=2)[CH2:13][CH2:12]1)=O)C1C=CC=CC=1>[Pd].CO>[O:26]1[C:25]2[CH:29]=[CH:30][C:22]([C:20]3[N:21]=[C:17]([CH:14]4[CH2:13][CH2:12][NH:11][CH2:16][CH2:15]4)[NH:18][C:19]=3[C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([CH3:37])[N:32]=3)=[CH:23][C:24]=2[O:28][CH2:27]1 | Cc1cccc(-c2[nH]c(C3CCN(C(=O)OCc4ccccc4)CC3)nc2-c2ccc3c(c2)OCO3)n1 | null | null | [Pd] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | null | 4 | Palladium on activated carbon (0.010 g) was added to a solution of 4-(4-benzo[1,3]dioxol-5-yl-5-(6-methyl-pyridin-2-yl)-1H-imidazol-2-yl)-piperidine-1-carboxylic acid benzyl ester (0.100 g, 0.20 mmol; see Example 5) in methanol (5 mL). The reaction mixture was stirred under hydrogen atmosphere for 4 hours. The mixture was then filtered and concentrated to give 0.070 g (97%) of the title compound as a yellow oil. MS (ESP+) m/z 363.2 (M+1). 1H NMR (300 MHz, CDCl3) δ 7.41 (t, 1H, J=7.8 Hz), 7.29 (d, 1H, J=8.1 Hz), 7.10 (m, 2H), 6.92 (d, 1H, J=7.5 Hz), 6.83 (m, 1H), 5.98 (s, 2H), 3.18 (m, 2H), 2.95 (m, 1H), 2.73 (m, 2H), 2.46 (s, 3H), 1.96 (m, 2H), 1.82 (m, 2H). | Cc1cccc(-c2[nH]c(C3CCNCC3)nc2-c2ccc3c(c2)OCO3)n1 | null | 96.6 | null |
644,030 | ord_dataset-c975a50a7600448fabd558f4a94a3e29 | null | 2004-01-01T00:08:00 | true | Br[C:2]1[C:3]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[Cl:15])=[CH:4][C:5]([Cl:8])=[N:6][CH:7]=1.C([Li])CCC.BrBr.[Li].Cl[C:25]([O:27][CH2:28][CH3:29])=[O:26]>O1CCCC1>[CH2:28]([O:27][C:25](=[O:26])[C:2]1[C:3]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[Cl:15])=[CH:4][C:5]([Cl:8])=[N:6][CH:7]=1)[CH3:29] | CCOC(=O)Cl | Clc1cc(-c2ccccc2Cl)c(Br)cn1 | null | BrBr | [Li] | [Li]CCCC | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | -78 | 1 | To a solution of 2.00 g (6.60 mmol) 5-bromo-2-chloro-4-(2-chloro-phenyl)-pyridine in 66 ml tetrahydrofuran 4.3 ml of a solution of n-butyllithium in hexanes (1.6 M, 6.9 mmol) were added dropwise at −100° C. under argon. Thin layer chromatography showed complete bromine-lithium exchange after 5 min. After addition of 0.71 ml (7.3 mmol) ethyl chloroformate the reaction mixture was allowed to slowly warm to −78° C. and stirred at that temperature for 1 h. The reaction mixture was allowed to warm to room temperature over night. Quenching with a small amount of water was followed by dilution with tert-butyl methyl ether and washing with water and brine. The organic layer was dried with sodium sulfate and concentrated. Column chromatography afforded 1.66 g (85%) of the title compound as a light yellow solid. | CCOC(=O)c1cnc(Cl)cc1-c1ccccc1Cl | null | 84.9 | null |
1,247,032 | ord_dataset-c544c0c663f54dbea4ddb52ddde7934e | null | 2013-01-01T00:01:00 | true | Br[C:2]1[CH:3]=[CH:4][C:5]([C:10]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[C:23]([CH3:24])=[CH:22][C:21]([CH3:25])=[CH:20][N:19]=3)[CH2:14][CH2:13]2)=[O:11])=[C:6]([CH:9]=1)[C:7]#[N:8].[CH3:26][C@@H:27]1[CH2:31][O:30][C:29](=[O:32])[NH:28]1>>[C:7]([C:6]1[CH:9]=[C:2]([N:28]2[C@H:27]([CH3:26])[CH2:31][O:30][C:29]2=[O:32])[CH:3]=[CH:4][C:5]=1[C:10]([N:12]1[CH2:17][CH2:16][N:15]([C:18]2[C:23]([CH3:24])=[CH:22][C:21]([CH3:25])=[CH:20][N:19]=2)[CH2:14][CH2:13]1)=[O:11])#[N:8] | C[C@@H]1COC(=O)N1 | Cc1cnc(N2CCN(C(=O)c3ccc(Br)cc3C#N)CC2)c(C)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | By reaction and treatment in the same manner as in Example 149 and using 5-bromo-2-[4-(3,5-dimethylpyridin-2-yl)piperazine-1-carbonyl]benzonitrile (399 mg) described in Preparation Example 193 and (R)-4-methyloxazolidin-2-one (121 mg) described in Preparation Example 25, the title compound (326 mg) was obtained. | Cc1cnc(N2CCN(C(=O)c3ccc(N4C(=O)OC[C@H]4C)cc3C#N)CC2)c(C)c1 | null | 77.8 | null |
1,391,436 | ord_dataset-12dc3bd21bcf44d09e5b4249afe15161 | null | 2014-01-01T00:02:00 | true | [Si:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:16]=[C:17]([C:22]3[CH:27]=[CH:26][C:25]([N:28]([CH3:30])[CH3:29])=[CH:24][CH:23]=3)[C:18]([NH2:21])=[N:19][CH:20]=2)=[CH:11][CH:10]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Si:31]([O:38][C:39]1[CH:44]=[CH:43][C:42]([CH2:45][C:46](Cl)=[O:47])=[CH:41][CH:40]=1)([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32].O>CN(C)C1C=CN=CC=1.N1C=CC=CC=1>[Si:31]([O:38][C:39]1[CH:40]=[CH:41][C:42]([CH2:45][C:46]([NH:21][C:18]2[C:17]([C:22]3[CH:27]=[CH:26][C:25]([N:28]([CH3:30])[CH3:29])=[CH:24][CH:23]=3)=[N:16][C:15]([C:12]3[CH:11]=[CH:10][C:9]([O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])=[CH:14][CH:13]=3)=[CH:20][N:19]=2)=[O:47])=[CH:43][CH:44]=1)([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32] | CN(C)c1ccc(-c2nc(-c3ccc(O[Si](C)(C)C(C)(C)C)cc3)cnc2N)cc1 | CC(C)(C)[Si](C)(C)Oc1ccc(CC(=O)Cl)cc1 | null | CN(C)c1ccncc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | c1ccncc1 | null | null | null | null | null | null | null | null | null | 50 | 20 | Under an argon atmosphere, to a mixture of 5-[4-(tert-butyldimethylsilyloxy)phenyl]-3-[4-(dimethylamino)phenyl]pyrazin-2-amine (7n) (315 mg, 749 μmol) and 4-(dimethylamino)pyridine (14.8 mg, 121 μmol) dissolved in anhydrous pyridine (15 mL) was added 2-[4-(tert-butyl dimethylsilyloxy)phenyl]acetyl chloride (10) prepared above at 0° C. and the mixture was hetated with stirring at 50° C. for 20 hours. After cooling to room temperature, to this was added water and the product was extracted with ethyl acetate (100 mL×3). The combined organic extract was washed successively with water (200 mL) and brine (200 mL), followed by drying over anhydrous sodium sulfate. After filtration and concentration under reduced pressure, the residue was purified by column chromatography (silica gel 50 g, n-hexane/ethyl acetate=2/1) to give Compound 11n (200 mg, 300 μmol, 40.0%) as a yellow solid. Rf=0.26 (n-hexane/ethyl acetate=2/1); 1H NMR (400 MHz, DMSO-d6) δ 0.17 (s, 6H), 0.23 (s, 6H), 0.95 (s, 9H), 0.97 (s, 9H), 2.95 (s, 6H), 3.50 (s, 2H), 6.52-6.65 (AA′BB′, 2H), 6.75-6.85 (AA′BB′, 2H), 6.95-7.05 (AA′BB′, 2H), 7.10-7.20 (AA′BB′, 2H), 7.56-7.66 (AA′BB′, 2H), 8.04-8.10 (AA′BB′, 2H), 8.82 (s, 1H), 10.41 (s, 1H); 13C NMR (67.8 MHz, DMSO-d6) δ −4.5 (2C), −4.6 (2C), 17.9, 18.0, 25.5 (6C), 39.8 (2C), 41.8, 111.3 (2C), 119.5 (2C), 120.3 (2C), 124.4, 128.05, 128.07 (2C), 128.9 (2C), 129.2, 130.4 (2C), 135.8, 142.0, 147.78, 147.84, 150.5, 153.8, 156.6, 169.3; IR (KBr, cm−1) 527, 685, 781, 839, 914, 1080, 1167, 1256, 1371, 1441, 1508, 1607, 1668, 2857, 2928, 2955, 3233. | CN(C)c1ccc(-c2nc(-c3ccc(O[Si](C)(C)C(C)(C)C)cc3)cnc2NC(=O)Cc2ccc(O[Si](C)(C)C(C)(C)C)cc2)cc1 | null | 40 | null |
125,536 | ord_dataset-fd44e5eeeeb4473cb5fbff2d885d7833 | null | 1985-01-01T00:01:00 | true | Cl[CH2:2][C:3]1[N:4]=[C:5]([F:27])[N:6]([C:8]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:7]=1.[CH3:28][SH:29].C(N(CC)CC)C>C1COCC1>[F:27][C:5]1[N:6]([C:8]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:7]=[C:3]([CH2:2][S:29][CH3:28])[N:4]=1 | Fc1nc(CCl)cn1C(c1ccccc1)(c1ccccc1)c1ccccc1 | CS | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | CCN(CC)CC | null | null | null | null | null | null | null | null | null | null | null | 4-Chloromethyl-2-fluoro-1-triphenylmethylimidazole was treated with methanethiol and triethylamine in THF solution to give 2-fluoro-4-methylthiomethyl-1-triphenylmethylimidazole. This was condensed with t-butyl 3-acetoxymethyl-7-aminoceph-3-em-4-carboxylate as for the starting material of Example 42 to give t-butyl 3-acetoxymethyl-7-(4-methylthiomethylimidazol-2-yl)aminoceph-3-em-4-carboxylate, having the following n.m.r. spectrum in d6DMSO: 1.5 (s, 9H); 2.0 (s, 6H); 3.5 (d, 2H); 3.8 (d, 2H); 4.7 (d, 1H); 5.0 (d, 1H); 5.25 (d, 1H); 5.65 (d, 1H); 7.0 (s, 1H). | CSCc1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)c(F)n1 | null | null | null |
1,528,252 | ord_dataset-8c74302143c04eb9983e4b3a7ead2d72 | null | 2014-01-01T00:12:00 | true | CO[C:3]([C:5]1[C:6]([OH:30])=[C:7]2[C:12](=[CH:13][N:14]=1)[N:11]([C@@H:15]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH3:16])[C:10](=[O:23])[C:9]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[CH:8]2)=[O:4].[NH2:31][CH2:32][CH2:33][C:34]([OH:36])=[O:35].C[O-].[Na+]>>[OH:30][C:6]1[C:5]([C:3]([NH:31][CH2:32][CH2:33][C:34]([OH:36])=[O:35])=[O:4])=[N:14][CH:13]=[C:12]2[C:7]=1[CH:8]=[C:9]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:10](=[O:23])[N:11]2[C@@H:15]([C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)[CH3:16] | COC(=O)c1ncc2c(cc(-c3ccccc3)c(=O)n2[C@H](C)c2ccccc2)c1O | NCCC(=O)O | null | C[O-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | 25 | null | A mixture of (R)-5-hydroxy-2-oxo-3-phenyl-1-(1-phenyl-ethyl)-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (30 mg, 0.075 mmol), β-alanine (535 mg, 6.0 mmol) and NaOMe solution (9 mL, 4.5 mmol, 0.5 M in MeOH) was refluxed for 16 h. After the mixture was cooled to r.t., the solvent was evaporated in vacuo. The residue was partitioned between EtOAc and water. 1 M HCl was added with vigorous stirring until pH was about 3. The aqueous layer was extracted with additional EtOAc, and the organic layers were combined, dried over MgSO4 and concentrated. The crude product was dissolved in saturated NaHCO3 and washed several times with ether. The aqueous layer was acidified to pH about 3, and the resulting precipitate was isolated by filtration to give 22 mg of the title compound. MS: (+) m/z 458.36 (M+1). | C[C@H](c1ccccc1)n1c(=O)c(-c2ccccc2)cc2c(O)c(C(=O)NCCC(=O)O)ncc21 | null | 64.1 | null |
918,960 | ord_dataset-8e59bd24817446f7b1c68e805b8e5f1d | null | 2009-01-01T00:11:00 | true | [CH2:1]([O:3][C:4]([C:6]1[NH:7][CH:8]=[CH:9][CH:10]=1)=[O:5])[CH3:2].[Cl-].[Al+3].[Cl-].[Cl-].[Br:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[CH2:22][C:23](Cl)=[O:24]>ClC(Cl)C>[CH2:1]([O:3][C:4]([C:6]1[NH:7][CH:8]=[C:9]([C:23](=[O:24])[CH2:22][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[Br:15])[CH:10]=1)=[O:5])[CH3:2] | CCOC(=O)c1ccc[nH]1 | O=C(Cl)Cc1ccccc1Br | null | [Al+3] | [Cl-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(Cl)Cl | null | null | null | null | null | null | null | null | null | null | 0 | null | Ethylpyrrole-2-carboxylate (1.9428 g, 13.96 mmol) in a minimal amount (5 mL) of dichloroethane was added to an ice cooled stirring mixture of aluminum chloride (4.0458 g, 30.34 mmol) and 2-bromophenylacetyl chloride (6.7116 g, 28.74 mmol) in dichloroethane (44 mL, 0.66 M) under N2. The ice bath was removed, and the reaction was stirred at room temperature for 2 h. 19.2977 g (2.6 mMol/g) Polyamine resin HL (200-400 mesh) and dichloroethane (20 mL) were added, and the reaction was stirred for ˜100 min. The reaction was then filtered through a glass-fritted funnel directly into ice water. The resin was rinsed with CH2Cl2, then the organic layers were removed, dried with Na2SO4, filtered, concentrated, and purified by silica gel chromatography (Combiflash column, 80:20 to 60:40 Hexanes:EtOAc) to obtain 2.5751 g (54.9%) 63 as a white solid. Note: A small amount of CH2Cl2 was required to solubilize the crude product before placement on the silica column. 1H (CDCl3, 400 MHz): δ 10.32 (1H, broad s), 7.57-7.53 (2H, m), 7.38-7.37 (1H, m), 7.29-7.21 (2H, m), 7.13-7.07 (1H, m), 4.35 (2H, q, J=7.2 Hz), 4.25 (2H, s), 1.36 (3H, t, J=7.2 Hz) ppm. 13C (CDCl3, 100 MHz): δ 191.78, 161.04, 134.91, 132.62, 131.66, 128.59, 127.40, 126.95, 126.25, 124.98, 124.17, 114.88, 60.92, 46.56, 14.26 ppm. DEPT (CDCl3, 100 MHz): CH3 carbons: 14.26; CH2 carbons: 60.92, 46.56; CH carbons: 132.62, 131.66, 128.59, 127.40, 126.95, 114.88 ppm. HPLC: 10.078 min. | CCOC(=O)c1cc(C(=O)Cc2ccccc2Br)c[nH]1 | null | 54.9 | null |
74,625 | ord_dataset-b9d8ddf9c2884d40859b6b5f24815a7d | null | 1980-01-01T00:12:00 | true | [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[O:12][CH3:13])[C:6](Cl)=[O:7].[CH2:14]([N:16]([CH:22]1[CH2:31][CH2:30][C:29]2[C:24](=[CH:25][CH:26]=[C:27]([O:32][CH3:33])[CH:28]=2)[CH2:23]1)[CH2:17][CH2:18][CH2:19][CH2:20][OH:21])[CH3:15].C(N(CC)CC)C>C1C=CC=CC=1>[CH2:14]([N:16]([CH:22]1[CH2:31][CH2:30][C:29]2[C:24](=[CH:25][CH:26]=[C:27]([O:32][CH3:33])[CH:28]=2)[CH2:23]1)[CH2:17][CH2:18][CH2:19][CH2:20][O:21][C:6](=[O:7])[C:5]1[CH:9]=[CH:10][C:11]([O:12][CH3:13])=[C:3]([O:2][CH3:1])[CH:4]=1)[CH3:15] | COc1ccc(C(=O)Cl)cc1OC | CCN(CCCCO)C1CCc2cc(OC)ccc2C1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | c1ccccc1 | CCN(CC)CC | null | null | null | null | null | null | null | null | null | 25 | 0.5 | 2.9 g of 3,4-dimethoxybenzoic acid and 4 ml of thionyl chloride were heated for 4 hours at reflux and concentrated under reduced pressure to obtain 3,4-dimethoxybenzoyl chloride. The 3,4-dimethoxybenzoyl chloride was dissolved in 10 ml of anhydrous benzene, and the resulting solution was added dropwise to a solution of 4.0 g of N-ethyl-N-(4-hydroxybutyl)-6-methoxy-1,2,3,4-tetrahydro-2-naphthylamine and 2.2 g of triethylamine in 50 ml of anhydrous benzene. After the addition, the resulting solution was stirred for 30 minutes at room temperature (about 25° C.) and heated for 3.5 hours at reflux. The reaction solution was washed with water, a 2 N-NaOH aqueous solution and water in this order, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue obtained was purified through silica gel chromatography to obtain N-ethyl-N-[4-(3,4-dimethoxybenzoyloxy)butyl]-6-methoxy-1,2,3,4-tetrahydro-2-naphthylamine as a colorless oily product. To this oily product was added an ethanolic solution of hydrogen chloride having a concentration of about 18% and the resulting solution was concentrated under reduced pressure to obtain a residue. The residue was dissolved in a mixed solvent of acetone and diethyl ether, and the solution was left at a temperature of about 2° to 3° C. to form crystals. By collecting the crystals through filtration and recrystallization from a mixed solvent of acetone and diethyl ether, 3.0 g of N-ethyl-N-[4-(3,4-dimethoxybenzoyloxy)butyl]-6-methoxy-1,2,3,4-tetrahydro-2-naphthylamine hydrochloride was obtained as colorless crystals having a melting point of 139°-140° C. The melting point, the infrared spectra and other physical data of this product corresponded to the date of the compound obtained in Example 2 (ii). | CCN(CCCCOC(=O)c1ccc(OC)c(OC)c1)C1CCc2cc(OC)ccc2C1 | null | null | null |
994,885 | ord_dataset-b6d8835b0c934476a36e6149e7597487 | null | 2010-01-01T00:09:00 | true | Br[C:2]1[CH:7]=[CH:6][C:5]([C:8](=[C:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)[C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[C:11]([F:16])[CH:10]=2)=[CH:4][CH:3]=1.[C:23]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])(=[O:26])[CH:24]=[CH2:25].CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.CCN(CC)CC>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[C:17]1(=[C:8]([C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[C:11]([F:16])[CH:10]=2)[C:5]2[CH:6]=[CH:7][C:2](/[CH:25]=[CH:24]/[C:23]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])=[CH:3][CH:4]=2)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1 | C=CC(=O)OC(C)(C)C | Oc1ccc(C(=C2CCCCC2)c2ccc(Br)cc2)cc1F | null | [Pd+2] | CC(=O)[O-] | Cc1ccccc1P(c1ccccc1C)c1ccccc1C | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(CC)CC | O | null | null | null | null | null | null | null | null | null | 140 | null | A mixture of 83 (317 mg, 0.877 mmol), tert-butyl acrylate (0.369 mL, 2.55 mmol), palladium acetate (15.0 mg, 0.067 mmol), P(o-tolyl)3 (40.0 mg, 0.131 mmol), and Et3N (0.520 mL, 3.73 mmol) were heated under microwave irradiation at 140° C. for 30 min. Water (30 mL) was added and the mixture was extracted with ether (3×20 mL). The combined ethereal extracts were washed with water (30 mL), brine (30 mL), and dried over MgSO4. Concentration followed by flash chromatography (20:1 to 5:1 hexanes:EtOAc) afforded 190 mg (54%) of 84. 1H NMR (400 MHz, CDCl3): δ 1.52 (s, 9H), 1.57-1.60 (m, 6H), 2.23 (m, 4H), 5.07 (d, 1H), 6.31 (d, J=16 Hz, 1H), 6.78 (m, 2H), 6.90 (t, J=8.6 Hz, 1H), 7.09 (d, J=8.1 Hz, 2H), 7.40 (d, J=8.1 Hz, 2H), 7.54 (d, J=16.0 Hz, 1H). | CC(C)(C)OC(=O)/C=C/c1ccc(C(=C2CCCCC2)c2ccc(O)c(F)c2)cc1 | null | 53 | null |
852,186 | ord_dataset-171b840ae6e84e45bab43b987d09f5c7 | null | 2008-01-01T00:11:00 | true | [C:1]([O:5][C:6](=[O:22])[NH:7][C@H:8]1[CH2:13][C@H:12]([CH3:14])[CH2:11][N:10](CC2C=CC=CC=2)[CH2:9]1)([CH3:4])([CH3:3])[CH3:2]>[Pd].C(O)C>[C:1]([O:5][C:6](=[O:22])[NH:7][C@H:8]1[CH2:13][C@H:12]([CH3:14])[CH2:11][NH:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3] | C[C@H]1C[C@H](NC(=O)OC(C)(C)C)CN(Cc2ccccc2)C1 | null | null | [Pd] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | null | null | null | null | null | null | null | null | null | null | 45 | null | A 40 L pressure vessel is charged with 0.6 Kg 50% wet, solid palladium on carbon (E101, 10 wt. %) under flow of nitrogen. A solution of 3.2 Kg intermediate (7) in 13.7 Kg of absolute ethanol is then charged to the reactor under nitrogen. The reactor is purged with nitrogen and is then pressurized with hydrogen at 45 psi. The reaction is then heated to 45° C. while maintaining a hydrogen pressure of 45 psi. The reaction is monitored by TLC or LC until complete. The reaction is cooled to ambient temperature, vented, and purged with nitrogen. The reactor contents are filtered through a bed of Celite and the solids are washed with 2.8 Kg of absolute ethanol. The filtrate is concentrated by rotary evaporation under vacuum until a waxy solid is obtained to afford intermediate (8): TLC Rf (Silica F254, 70:30 v/v ethyl acetate-hexanes, KMnO4 stain)=0.12; 1H NMR (300 MHz, CDCl3) δ5.31 (br s, 1H), 3.80-3.68 (m, 1H), 2.92 (d, J=11.4 Hz,1H), 2.77 (AB quart, JAB=12.0 Hz, Δv=50.2 Hz, 2H), 2.19 (t, J=10.7 Hz, 1H), 1.82-1.68 (m, 2H), 1.54 (br s, 1H), 1.43 (s, 9H), 1.25-1.15 (m, 1H), 0.83 (d, J=6.6 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 155.3, 78.9, 54.3, 50.8, 45.3, 37.9, 28.4, 27.1, 19.2; MS (ESI+) m/z 215 (M+H), 429 (2M+H). | C[C@@H]1CNC[C@@H](NC(=O)OC(C)(C)C)C1 | null | null | null |
1,136,442 | ord_dataset-aaeaab5f3720492494c1cbbdd0ed2820 | null | 2012-01-01T00:02:00 | true | COC(C1C=C(O[C:16]2[CH:21]=[CH:20][C:19]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:18][CH:17]=2)C=C2OC(C)CC=12)=O.[CH3:26][O:27][C:28]([C:30]1[CH:40]=[C:39]([OH:41])[C:33]2[CH2:34][C:35]([CH3:38])([CH3:37])[O:36][C:32]=2[C:31]=1[F:42])=[O:29]>>[CH3:26][O:27][C:28]([C:30]1[CH:40]=[C:39]([O:41][C:16]2[CH:21]=[CH:20][C:19]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:18][CH:17]=2)[C:33]2[CH2:34][C:35]([CH3:38])([CH3:37])[O:36][C:32]=2[C:31]=1[F:42])=[O:29] | COC(=O)c1cc(O)c2c(c1F)OC(C)(C)C2 | COC(=O)c1cc(Oc2ccc(S(C)(=O)=O)cc2)cc2c1CC(C)O2 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The title compound was prepared in a similar manner as described for Intermediate 1f, from 7-fluoro-4-hydroxy-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid methyl ester (190a). 1H NMR (400 MHz, CDCl3) δ 7.89-7.94 (m, 2 H) 7.10 (d, J=4.55 Hz, 1 H) 7.04-7.09 (m, 2 H) 3.92 (s, 3 H) 3.07 (s, 3 H) 2.92 (s, 2 H) 1.54 (s, 6 H); LCMS for C22H22FN3O5S m/z 395.00 (M+H)+. | COC(=O)c1cc(Oc2ccc(S(C)(=O)=O)cc2)c2c(c1F)OC(C)(C)C2 | null | null | null |
235,726 | ord_dataset-1acb071a357f438ea5993287375971cf | null | 1991-01-01T00:10:00 | true | [OH:1][C:2]1[C:11]([OH:12])=[N:10][C:9]2[C:8]3=[N:13]O[N:15]=[C:7]3[CH:6]=[CH:5][C:4]=2[N:3]=1.C(N(CC)CC)C>CN(C)C=O.[Pd]>[NH2:13][C:8]1[C:7]([NH2:15])=[CH:6][CH:5]=[C:4]2[C:9]=1[N:10]=[C:11]([OH:12])[C:2]([OH:1])=[N:3]2 | Oc1nc2ccc3nonc3c2nc1O | null | null | [Pd] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | CCN(CC)CC | null | null | null | null | null | null | null | null | null | null | null | A solution of 5,0 g (24,5 mmol) 7,8-dihydroxy-1,2,5-oxadiazolo(3,4-f)quinoxaIine and 6,8 ml (49 mmol) triethylamine in 500 ml dimethylformamide was hydrogenated at atm. pressure using 5% Pd-C (0,5 g) as a catalyst. The reaction mixture was filtered and evaporated in vacuo. The residue was stirred with water, and the precipitate was filtered off to give 4,5 g (96%) 5,6-diamino-2,3-dihydroxyquinoxaline, m.p. >300° C. NMR (DMSO-d6) 11.0 (2H, broad m), 6.43 (1H,d), 6.23 (1H,d), 4.5 (4H, broad m). | Nc1ccc2nc(O)c(O)nc2c1N | null | 95.6 | null |
1,510,119 | ord_dataset-1a1aa5d1c3224edca0aec6e3398da985 | null | 2014-01-01T00:11:00 | true | CS([C:4]1[N:5]=[CH:6][C:7]2[CH2:12][N:11]([C:13]3[CH:18]=[CH:17][N:16]=[C:15]([C:19]([NH:21][C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=4)=[O:20])[CH:14]=3)[CH2:10][C:8]=2[N:9]=1)=O.CS(C1[N:37]=CC2CN(C3C=CN=C(C(NC4C=CC=C(C(F)(F)F)C=4)=O)C=3)CC=2N=1)(=O)=O.[OH-].[NH4+]>O1CCOCC1>[F:29][C:28]([F:31])([F:30])[C:24]1[CH:23]=[C:22]([NH:21][C:19]([C:15]2[CH:14]=[C:13]([N:11]3[CH2:12][C:7]4[CH:6]=[N:5][C:4]([NH2:37])=[N:9][C:8]=4[CH2:10]3)[CH:18]=[CH:17][N:16]=2)=[O:20])[CH:27]=[CH:26][CH:25]=1 | CS(=O)c1ncc2c(n1)CN(c1ccnc(C(=O)Nc3cccc(C(F)(F)F)c3)c1)C2 | CS(=O)(=O)c1ncc2c(n1)CN(c1ccnc(C(=O)Nc3cccc(C(F)(F)F)c3)c1)C2 | null | [NH4+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1COCCO1 | null | null | null | null | null | null | null | null | null | null | 90 | null | A mixture of 4-(2-(Methylsulfinyl)-5H-pyrrolo[3,4-d]pyrimidin-6(7H)-yl)-N-(3-(trifluoromethyl)phenyl)picolinamide and 4-(2-(methylsulfonyl)-5H-pyrrolo[3,4-d]pyrimidin-6(7H)-yl)-N-(3-(trifluoromethyl)phenyl)picolinamide was suspended in 1,4-dioxane (7 mL). Ammonium hydroxide (30%, 1.5 mL) was added and the reaction was heated at 90° C. for 16 hours. TLC indicated only partial conversion to the desired amine. The solvent was reduced with a nitrogen stream and then additional ammonium hydroxide (1 mL) was added. The reaction was sealed in a tube and heated at 100° C. for 17 h. The solvent was evaporated in vacuo. The resulting solid was triturated with water and then methanol. The solid was chromatographed on silica gel (4 g) eluted with ethyl acetate:methanol (9:1) to give the title compound (10.6 mg, 0.026 mmol). | Nc1ncc2c(n1)CN(c1ccnc(C(=O)Nc3cccc(C(F)(F)F)c3)c1)C2 | null | null | null |
329,964 | ord_dataset-2c460e2ef9934444aaf26fec1f75741f | null | 1996-01-01T00:05:00 | true | [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:14]3[CH:15]=[C:16]4[O:21][CH2:20][O:19][C:17]4=[CH:18][C:13]=3[CH2:12][C:11]([CH3:22])=[N:10][N:9]=2)=[CH:4][CH:3]=1.[C:23](OC(=O)C)(=[O:25])[CH3:24]>C(O)C>[C:23]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:14]3[CH:15]=[C:16]4[O:21][CH2:20][O:19][C:17]4=[CH:18][C:13]=3[CH2:12][C:11]([CH3:22])=[N:10][N:9]=2)=[CH:4][CH:3]=1)(=[O:25])[CH3:24] | CC(=O)OC(C)=O | CC1=NN=C(c2ccc(N)cc2)c2cc3c(cc2C1)OCO3 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | null | null | null | null | null | null | null | null | null | null | null | null | 10 g (34 mmol) of 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine were stirred for 3 hours with 100 ml of acetic anhydride. The crystals formed were filtered, washed with 5×10 ml of anhydrous ethanol and dried, yielding 9.2 g of raw product, m.p. 252°-254° C. (decomp.). This product was treated with 45 ml of hot 99.5% ethanol. After cooling the crystals were filtered, washed with 3×10 ml of ethanol and dried to give 8.68 g (76.1%) of the aimed product, m.p.: 256°-258° C. (decomp.). | CC(=O)Nc1ccc(C2=NN=C(C)Cc3cc4c(cc32)OCO4)cc1 | null | 76.1 | null |
1,711,155 | ord_dataset-3f2a531ffbae4b9eb1048afcd7953beb | null | 2016-01-01T00:04:00 | true | [F:1][C:2]([F:22])([C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=1)[C:3]([NH:5][C:6]1[CH:14]=[CH:13][CH:12]=[CH:11][C:7]=1[C:8]([NH2:10])=[O:9])=O.Cl[Si](C)(C)C>ClCCCl>[F:1][C:2]([F:22])([C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=1)[C:3]1[N:10]=[C:8]([OH:9])[C:7]2[C:6](=[CH:14][CH:13]=[CH:12][CH:11]=2)[N:5]=1 | NC(=O)c1ccccc1NC(=O)C(F)(F)c1ccc(F)cc1 | null | null | C[Si](C)(C)Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCCl | null | null | null | null | null | null | null | null | null | null | 85 | 8 | To a solution of 2-(2,2-difluoro-2-(4-fluorophenyl)acetamido)benzamide (0.95 g, 3.08 mmol) in DCE (25 mL), TEA (17.2 mL, 0.123 mol) and chlorotrimethylsilane (5.84 mL, 0.0462 mol) were added at rt. The reaction mixture was stirred at 85° C. overnight. After cooling to rt, the solid was filtered and the filtrate was concentrated to dryness. The residue was purified on a silica gel column, using DCM/MeOH as eluent. 2-(Difluoro(4-fluorophenyl)methyl)quinazolin-4-ol was obtained as an off white solid (0.668 g, 75%). 1H NMR (300 MHz, DMSO-d6) δ 7.39 (t, 2H), 7.62 (m, 1H), 7.78-7.71 (m, 3H), 7.84 (m, 1H), 8.16 (m, 1H), 13.11 (s, 1H). | Oc1nc(C(F)(F)c2ccc(F)cc2)nc2ccccc12 | null | null | null |
166,781 | ord_dataset-5c25f386f4664070a72d578feacedf86 | null | 1987-01-01T00:12:00 | true | [C:1]([C:5]1[CH:10]=[C:9]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH2:19][CH3:20])[CH:13]=2)[CH:8]=[C:7]([C:21]([CH3:24])([CH3:23])[CH3:22])[C:6]=1[OH:25])([CH3:4])([CH3:3])[CH3:2].[C:26]1(=[O:32])[O:31][C:29](=[O:30])[CH2:28][CH2:27]1.[OH-].[Na+].Cl>O>[C:1]([C:5]1[CH:10]=[C:9]([N:11]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH2:19][CH3:20])[CH:13]=2)[C:26]([CH2:27][CH2:28][C:29]([OH:31])=[O:30])=[O:32])[CH:8]=[C:7]([C:21]([CH3:24])([CH3:23])[CH3:22])[C:6]=1[OH:25])([CH3:3])([CH3:4])[CH3:2] | CCOc1cccc(Nc2cc(C(C)(C)C)c(O)c(C(C)(C)C)c2)c1 | O=C1CCC(=O)O1 | null | Cl | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | null | null | null | null | null | null | null | null | null | null | 140 | null | A mixture of 5 g (0.015 mole) of 2,6-di-tertiarybutyl-4-(3'-ethoxyanilino)phenol and 1.5 g (0.015 mole) of succinic anhydride was heated under a nitrogen atmosphere at 140° C. for two hours. The reaction was cooled to room temperature and the resulting glass was diluted with water. The addition of 100 ml of 10% sodium hydroxide failed to give a solution so the mixture was acidified with 10% hydrochloric acid. The resulting solid was collected and then recrystallized first from a mixture of ethanol and water and then from a mixture of diethyl ether and hexane to give 2.6 g of tan solid 3-[N-(3,5-di-tertiary-butyl-4-hydroxyphenyl)-N-(3-ethoxyphenyl)carbamoyl]propionic acid, m.p. 128°-130° C. Analysis: Calculated for C26H35NO5 : % C, 70.7; % H, 8.0; % N, 3.2; Found: % C, 70.5; % H, 7.8; % N, 3.4. | CCOc1cccc(N(C(=O)CCC(=O)O)c2cc(C(C)(C)C)c(O)c(C(C)(C)C)c2)c1 | null | 39.3 | null |
1,382,901 | ord_dataset-31641fb65b34430fa7435229b949b604 | null | 2014-01-01T00:01:00 | true | [OH:1][CH2:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=[O:8])=[C:5]([C:12]([F:15])([F:14])[F:13])[CH:4]=1.[C:16]1(C)C=CC=CC=1.S(=O)(=O)(O)O>CO>[CH3:16][O:8][C:7](=[O:9])[C:6]1[CH:10]=[CH:11][C:3]([CH2:2][OH:1])=[CH:4][C:5]=1[C:12]([F:13])([F:14])[F:15] | O=C(O)c1ccc(CO)cc1C(F)(F)F | Cc1ccccc1 | null | O=S(=O)(O)O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | 80 | 16 | To a solution of 4-hydroxymethyl-2-trifluoromethyl-benzoic acid (Example I8) (9.07 g) in methanol (250 ml) was added toluene (250 ml) and concentrated sulfuric acid (4.5 ml). The reaction mixture was stirred at 80° C. for 16 hours. The methanol was removed and the residue diluted with aqueous sodium hydrogen carbonate (saturated) (150 ml) and ethyl acetate (150 ml). The phases were separated and the aqueous layer was extracted with more ethyl acetate (2×150 ml). The combined organic extracts were washed with brine, dried over sodium sulfate and concentrated to give 4-hydroxymethyl-2-trifluoromethyl-benzoic acid methyl ester (5.97 g) as a colorless oil. 1H-NMR (CDCl3, 400 MHz): 8.76-7.27 (m, 3H), 4.78 (s, 2H), 3.93 (s, 3H), 2.5 (br s, 1H). | COC(=O)c1ccc(CO)cc1C(F)(F)F | null | null | null |
605,169 | ord_dataset-273fda773e864aaf9b71a30a2d9f2162 | null | 2003-01-01T00:08:00 | true | [OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[C:5]2[CH2:11][CH:12]([CH3:14])[CH3:13].C(=O)([O-])[O-].[K+].[K+].F[C:22]1[C:27]([CH3:28])=[CH:26][C:25]([N+:29]([O-:31])=[O:30])=[CH:24][C:23]=1[CH3:32]>CS(C)=O>[CH3:28][C:27]1[CH:26]=[C:25]([N+:29]([O-:31])=[O:30])[CH:24]=[C:23]([CH3:32])[C:22]=1[O:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[C:5]2[CH2:11][CH:12]([CH3:14])[CH3:13] | CC(C)Cc1n[nH]c2ccc(O)cc12 | Cc1cc([N+](=O)[O-])cc(C)c1F | null | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CS(C)=O | null | null | null | null | null | null | null | null | null | null | null | null | In an analogous manner to the procedure of Example XVIII, 136 mg (0.715 mmol) of 5-hydroxy-3-isobutyl-1H-indazole are reacted with 99 mg (0.715 mmol) of potassium carbonate and 121 mg (0.715 mmol) of 4-fluoro-3,5-dimethylnitrobenzene in 5 ml of DMSO to give 92 mg (38%) of 5-(2,6-dimethyl-4-nitrophenoxy)-3-isobutyl-1H-indazole. | Cc1cc([N+](=O)[O-])cc(C)c1Oc1ccc2[nH]nc(CC(C)C)c2c1 | null | 37.9 | null |
152,451 | ord_dataset-5944a40bb4504bbe8185cfdf2a811d03 | null | 1987-01-01T00:01:00 | true | [CH3:1][N:2]=[C:3]=[S:4].Cl.[NH2:6][CH2:7][C:8]([C:10]1[CH:15]=[C:14]([C:16]([CH3:19])([CH3:18])[CH3:17])[C:13]([OH:20])=[C:12]([C:21]([CH3:24])([CH3:23])[CH3:22])[CH:11]=1)=O>N1C=CC=CC=1>[C:21]([C:12]1[CH:11]=[C:10]([C:8]2[N:2]([CH3:1])[C:3]([SH:4])=[N:6][CH:7]=2)[CH:15]=[C:14]([C:16]([CH3:19])([CH3:18])[CH3:17])[C:13]=1[OH:20])([CH3:24])([CH3:23])[CH3:22] | CC(C)(C)c1cc(C(=O)CN)cc(C(C)(C)C)c1O | CN=C=S | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | c1ccncc1 | null | null | null | null | null | null | null | null | null | null | null | null | After stirring a mixture of 100 ml of pyridine, 6 g of methyl isothiocyanate, and 3 g of 4-(2-aminoacetyl)-2,6-di-tert-butylphenol hydrochloride at room temperature for 2 hours, the resulted mixture was maintained at an inside temperature of 80°-90° C. for 1.5 hours. The reaction mixture was concentrated udner reduced pressure and then the residue was extracted with 100 ml of ethyl acetate. The extract was washed with diluted hydrochloric acid, dried, and concentrated under reduced pressure. The residue was recrystallized from ethanol to provide 0.6 g of 5-(3,5-di-tert-butyl-4-hydroxyphenyl)-2-mercapto-1-methylimidazole. | Cn1c(-c2cc(C(C)(C)C)c(O)c(C(C)(C)C)c2)cnc1S | null | 18.8 | null |
1,698,044 | ord_dataset-54347fcace774f89850681d6dec8009f | null | 2016-01-01T00:03:00 | true | CCCC[N+](CCCC)(CCCC)CCCC.[F-].[Cl:19][C:20]1[C:25]([NH:26][C:27]2[N:32]=[C:31]([NH:33][CH:34]3[CH2:36][CH2:35]3)[C:30]3=[N:37][CH:38]=[C:39]([C:40]#[N:41])[N:29]3[N:28]=2)=[CH:24][C:23]([C:42]#[N:43])=[CH:22][C:21]=1[N:44]1[CH2:49][CH2:48][C@@H:47]([NH:50][S:51]([CH3:54])(=[O:53])=[O:52])[C@H:46]([O:55][Si](C(C)C)(C(C)C)C(C)C)[CH2:45]1>C1COCC1>[Cl:19][C:20]1[C:25]([NH:26][C:27]2[N:32]=[C:31]([NH:33][CH:34]3[CH2:35][CH2:36]3)[C:30]3=[N:37][CH:38]=[C:39]([C:40]#[N:41])[N:29]3[N:28]=2)=[CH:24][C:23]([C:42]#[N:43])=[CH:22][C:21]=1[N:44]1[CH2:49][CH2:48][C@@H:47]([NH:50][S:51]([CH3:54])(=[O:53])=[O:52])[C@H:46]([OH:55])[CH2:45]1 | CC(C)[Si](O[C@@H]1CN(c2cc(C#N)cc(Nc3nc(NC4CC4)c4ncc(C#N)n4n3)c2Cl)CC[C@H]1NS(C)(=O)=O)(C(C)C)C(C)C | null | null | CCCC[N+](CCCC)(CCCC)CCCC | [F-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | 25 | 8 | TBAF (1M in THF, 0.048 mL, 0.048 mmol) was added to a solution of N-((3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-3-((triisopropylsilyl)oxy)piperidin-4-yl)methanesulfonamide (28 mg, 0.040 mmol) in THF (2 mL) and the reaction mixture was stirred at room temperature overnight. Solvent was evaporated and the crude product was purified by flash chromatography on silica gel using an automated ISCO system (12 g column, eluting with 0-6% methanol/dichloromethane). N-((3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-3-hydroxypiperidin-4-yl)methanesulfonamide (21 mg) was obtained as a white solid. | CS(=O)(=O)N[C@@H]1CCN(c2cc(C#N)cc(Nc3nc(NC4CC4)c4ncc(C#N)n4n3)c2Cl)C[C@H]1O | null | 96.7 | null |
417,109 | ord_dataset-1cb9d78632144c5f8acfc3e9ff388678 | null | 1998-01-01T00:11:00 | true | C[O:2][C:3]([C:5]1[S:6][CH:7]=[CH:8][C:9]=1[CH2:10][CH3:11])=[O:4].[OH-].[Na+].O1CCCC1>CO>[CH2:10]([C:9]1[CH:8]=[CH:7][S:6][C:5]=1[C:3]([OH:4])=[O:2])[CH3:11] | CCc1ccsc1C(=O)OC | null | null | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | C1CCOC1 | null | null | null | null | null | null | null | null | null | 25 | 1 | 3-Acetyl-2-thiophenecarboxylic acid methyl ester (3.87 g) synthesized in this manner was dissolved in methanol (50 ml), and sodium borohydride (0.95 g) was added under ice-cooling. The mixture was stirred at room temperature for 1 hour, and 1N hydrochloric acid (50 ml) was added. The mixture was extracted with ethyl acetate, and the extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give 3-(1-hydroxyethyl)-2-thiophenecarboxylic acid methyl ester (3.77 g). This product was dissolved in ethyl acetate (100 ml), and methanesulfonyl chloride (2.86 g), triethylamine (3.5 g) and dimethylaminopyridine (0.2 g) were added. The mixture was stirred at room temperature for 2 hours, and 1N hydrochloric acid (50 ml) was added. The mixture was extracted with ethyl acetate, and the extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in acetone (100 ml), and sodium iodide (10 g) was added. The mixture was stirred at room temperature for 2 hours, and insoluble substances were removed by filtration. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography. The desired fractions were concentrated under reduced pressure to give 3-(1-iodoethyl)-2-thiophenecarboxylic acid methyl ester (3.0 g). 3-(1-iodoethyl)-2-thiophenecarboxylic acid methyl ester was dissolved in dimethylsulfoxide (10 ml), and sodium borohydride (0.4 g) was added at room temperature. The mixture was stirred for 1 hour, and 1N hydrochloric acid was added. The mixture was extracted with ethyl acetate, and the extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give 3-ethyl-2-thiophenecarboxylic acid methyl ester (1.0 g). A mixture of 3-ethyl-2-thiophenecarboxylic acid methyl ester (1.0 g), 1N aqueous sodium hydroxide (15 ml), tetrahydrofuran (30 ml) and methanol (10 ml) was stirred at room temperature for 1 hour. The mixture was washed with diethyl ether, and the aqueous layer was acidified with 1N hydrochloric acid and extracted with diethyl ether. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give 3-ethyl-2-thiophenecarboxylic acid (0.9 g) as crystals. | CCc1ccsc1C(=O)O | null | 98.1 | null |
390,098 | ord_dataset-44d518e567bd4c039d77233023f78bb2 | null | 1998-01-01T00:01:00 | true | [O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[CH2:17][OH:18])[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.[H-].[Na+].[C:21]1([CH2:27]Br)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>C1(C)C=CC=CC=1>[O:1]1[C:5]2([CH2:6][CH2:7][CH:8]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[CH2:17][O:18][CH2:27][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH2:9][CH2:10]2)[O:4][CH2:3][CH2:2]1 | BrCc1ccccc1 | OCc1ccccc1C1CCC2(CC1)OCCO2 | null | [H-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Cc1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | null | When the bridging group is carbonyl, the Grignard reagent of 8-bromo-1,4-dioxaspiro[4.5]decane is first prepared. The precursor 8-bromo-1,4-dioxaspiro[4.5]decane is prepared by the method of E. I. Snyder (JOC, 36, 403 (1971)). The Grignard reagent is in turn reacted with an appropriately substituted or unsubstituted benzaldehyde, for example, 3-trifluoromethylbenzaldehyde and then treated with aqueous ammonium chloride, yielding [(1,4-dioxaspiro[4.5]decan-8-yl)(phenyl)]methanol. The so-prepared alcohol is treated with sodium hydride in toluene, and then is reacted with phenylmethyl bromide, yielding phenylmethyl [(1,4-dioxaspiro[4.5]decan-8-yl)(phenyl)]methyl ether. The 1,4-dioxaspiro functional group is then cleaved from the so-prepared molecule with acetic acid and water, as previously described, affording the corresponding phenylmethyl [(cyclohexanon-4-yl)(phenyl)]methyl ether. The ether is then reacted with cyanoguanidine, as previously described, yielding the appropriate 2,4-diamino-6-[(phenylmethoxy)(phenyl)methyl]-5,6,7,8-tetrahydroquinazoline. The tetrahydroquinazoline is then cleaved with hydrogen gas in the presence of 5% palladium on charcoal, yielding the corresponding [(2,4-diamino-5,6,7,8-tetrahydroquinazolin-6-yl)(phenyl)]methanol. Using the method of D. Swern (Tetrahedron, 34, 1651-1660 (1978)), the methanol is oxidized with oxalyl chloride and dimethyl sulfoxide in methylene chloride, yielding the targeted 2,4-diamino-6-phenylcarbonyl-5,6,7,8-tetrahydroquinazoline. Example 9 provides a detailed description of how this reaction is conducted. | c1ccc(COCc2ccccc2C2CCC3(CC2)OCCO3)cc1 | null | null | null |
1,291,985 | ord_dataset-de51ecc8d4434bacaa8bc32d7d73484c | null | 2013-01-01T00:05:00 | true | [C:1]([NH:8][C@H:9]([C:18]([OH:20])=[O:19])[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[C:21](=O)([O-])[O-].[K+].[K+].S(OC)(OC)(=O)=O>CC(C)=O>[C:4]([O:3][C:1]([NH:8][C@@H:9]([CH2:10][C:11]1[CH:12]=[CH:13][C:14]([Cl:17])=[CH:15][CH:16]=1)[C:18]([O:20][CH3:21])=[O:19])=[O:2])([CH3:5])([CH3:7])[CH3:6] | CC(C)(C)OC(=O)N[C@@H](Cc1ccc(Cl)cc1)C(=O)O | O=C([O-])[O-] | null | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(C)=O | COS(=O)(=O)OC | null | null | null | null | null | null | null | null | null | null | 36 | To a 250 mL round bottom flask was added N-Boc-4-chloro-L-phenylalanine (0.971 g, 3.24 mmol), potassium carbonate (0.448 g, 3.24 mmol), a stir bar and 30 ml of acetone. To this was added dimethyl sulfate (0.613 ml, 6.48 mmol) and the reaction was allowed to proceed at ambient temperature for 36 h. The reaction was quenched with water (15 ml), and the product was extracted with ethyl acetate (4×100 ml). The organics were pooled, washed with brine, and dried over sodium sulfate. The organics were filtered and concentrated in vacuo to provide a pale yellow residue. The residue was purified by column chromatography on a Biotage SP1, 40M Biotage silica cartridge, eluting with a linear gradient of hexanes-ethyl acetate to provide the title compound as a pale yellow foam (950 mg). Mass spectrum (ESI) 214.1 (M-Boc). 1H NMR (600 MHz, CDCl3): δ 7.24 (d, J=8.3 Hz, 2H), 7.06 (d, J=8.1 Hz, 1H), 4.96 (d, J=7 Hz, 1H), 4.56 (d, J=6 Hz, 1H), 3.71 (s, 3H), 3.08 (dd, J=5.7, 5.7 Hz, 2H), 3.01 (dd, J=5.9, 6.0 Hz, 1H), 1.42 (s, 9H). | COC(=O)[C@H](Cc1ccc(Cl)cc1)NC(=O)OC(C)(C)C | null | 93.4 | null |
1,651,815 | ord_dataset-42cd9bc5aae3485f9a58f1527bd3abf0 | null | 2015-01-01T00:11:00 | true | [CH:1]1([NH:5][C:6]2[N:7]=[N:8][C:9]([C:12]#[CH:13])=[CH:10][CH:11]=2)[CH2:4][CH2:3][CH2:2]1.[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[NH:25][C:24]3[CH:26]=[C:27]([CH2:30][N:31]4[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]4)[CH:28]=[CH:29][C:23]=3[N:22]=2)=[CH:17][C:16]=1I>>[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[NH:25][C:24]3[CH:26]=[C:27]([CH2:30][N:31]4[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]4)[CH:28]=[CH:29][C:23]=3[N:22]=2)=[CH:17][C:16]=1[C:13]#[C:12][C:9]1[N:8]=[N:7][C:6]([NH:5][CH:1]2[CH2:4][CH2:3][CH2:2]2)=[CH:11][CH:10]=1 | C#Cc1ccc(NC2CCC2)nn1 | CN1CCN(Cc2ccc3nc(-c4ccc(Cl)c(I)c4)[nH]c3c2)CC1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The title compound was synthesized from N-cyclobutyl-6-ethynylpyridazin-3-amine and 2-(4-chloro-3-iodophenyl)-6-((4-methylpiperazin-1-yl)methyl)-1H-benzo[d]imidazole in a manner similar to that described for in Example 1. The title compound was obtained as a pale yellow solid. Mp:161-163° C.; 1H NMR (300 MHz, CDCl3) δ: 8.13-8.15 (1 H, d, J=6.0 Hz), 7.95 (1 H, s), 7.62-7.65 (1 H, d, J=9.0 Hz), 7.65 (1 H, s), 7.36-7.39 (1 H, d, J=9.0 Hz), 7.29-7.32 (1 H, d, J=9.0 Hz), 7.18-7.21 (1 H, d, J=9.0 Hz), 6.63-6.66 (1 H, d, J=9.0 Hz), 5.80 (1 H, s), 4.28-4.30 (1 H, m), 3.63 (2 H, s), 2.63 (8 H, brs), 2.40-2.44 (2 H, m) 2.40 (3 H, s), 1.96-2.02 (2 H, m), 1.79-1.81 (2 H, m). HRMS (ESI-TOF+): m/z [M+H]+ calcd for C29H31ClN7: 512.2324. found: 512.2303. | CN1CCN(Cc2ccc3nc(-c4ccc(Cl)c(C#Cc5ccc(NC6CCC6)nn5)c4)[nH]c3c2)CC1 | null | null | null |
112,324 | ord_dataset-5237a168f9214b7ca3db5a1dc3e62d07 | null | 1983-01-01T00:12:00 | true | [Cl:1][C:2]1[CH:3]=[N:4][C:5](=[S:8])[NH:6][CH:7]=1.C(N(CC)CC)C.[CH2:16]([CH:18]1[O:20][CH2:19]1)[Cl:17]>ClCCl>[OH:20][CH:18]([CH2:16][Cl:17])[CH2:19][S:8][C:5]1[N:6]=[CH:7][C:2]([Cl:1])=[CH:3][N:4]=1 | ClCC1CO1 | S=c1ncc(Cl)c[nH]1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | CCN(CC)CC | null | null | null | null | null | null | null | null | null | 25 | 3 | A mixture of 5-chloropyrimidine-2-thione (14 mmol) and triethylamine (14 mmol) was stirred together in dichloromethane (30 ml) for 5 min before epichlorohydrin (15 mmol) was added. The mixture was stirred at room temperature for 3 h, the solvent evaporated, the residue triturated with water, the insoluble material extracted with chloroform, the dried (MgSO4) chloroform solution evaporated and the residue crystallized from chloroform:pet. ether; yield 30%, m.p. 99° C. 1H NMR (acetone-d6): δ3.3-3.8 (2CH2, m) 3.9-4.4 (CH, m), 4.6-4.7 (OH), 8.59 (H-4, H-6). | OC(CCl)CSc1ncc(Cl)cn1 | null | 30 | null |
67,490 | ord_dataset-b5f1497361c94e5fa55257200189a6a4 | null | 1980-01-01T00:06:00 | true | [Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([OH:12])=[CH:4][CH:3]=1.Cl[CH2:14][CH:15]1[CH2:17][O:16]1.[OH-].[K+]>O>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][CH2:14][CH:15]2[CH2:17][O:16]2)=[CH:4][CH:3]=1 | Oc1ccc(Cl)c2ccccc12 | ClCC1CO1 | null | [K+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | null | null | null | null | null | null | null | null | null | null | null | null | To a stirred mixture of 44.5 parts of 4-chloro-1-naphthalenol and 115 parts of 2-(chloromethyl)oxirane are added portionwise 17.1 parts of potassium hydroxide (exothermic reaction). When the exothermic reaction is ceased, the whole is heated to reflux and stirred at reflux temperature for 2 hours. Water is added and the whole is extracted twice with trichloromethane. The combined extracts are washed three times with water, dried and evaporated. The residue is distilled, yielding 45.3 parts of 2-[(4-chloro-1-naphthalenyloxy)methyl]oxirane; bp. 150°-151° C. at 0.2 mm. pressure. | Clc1ccc(OCC2CO2)c2ccccc12 | null | null | null |
872,189 | ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b | null | 2009-01-01T00:03:00 | true | CI.[CH3:3][C:4]([C:6]1[CH:11]=[CH:10][C:9]([Br:12])=[CH:8][C:7]=1[OH:13])=O.[C:14](=O)([O-])[O-].[K+].[K+].NN.[OH-].[K+]>CC(C)=O>[Br:12][C:9]1[CH:10]=[CH:11][C:6]([CH2:4][CH3:3])=[C:7]([O:13][CH3:14])[CH:8]=1 | CC(=O)c1ccc(Br)cc1O | O=C([O-])[O-] | null | NN | [K+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(C)=O | CI | null | null | null | null | null | null | null | null | null | 25 | 18 | Methyl iodide (3 mL, 47.3 mmol) was added to a solution of 4-bromo-2-hydroxyacetophenone (9.25 g, 43 mmol) and potassium carbonate (6.54 g, 47.3 mmol) in acetone (20 mL) and the mixture was stirred at room temperature for 18 hours. The reaction mixture was concentrated in vacuo to low volume and diluted with water. The aqueous mixture was extracted with dichloromethane (3×50 mL) and the combined organic solution was washed with water, dried over sodium sulfate and concentrated in vacuo. The residue was dissolved in 1,2-ethanediol (10 mL), hydrazine (19.47 mL, 400 mmol) and potassium hydroxide (7.86 g, 140 mmol) were added and the reaction mixture was heated at 150° C. for 60 hours. The reaction mixture was then quenched with 1M hydrochloric acid and extracted with ethyl acetate (3×20 mL). The combined organic solution was dried over sodium sulfate, concentrated in vacuo and the residue was purified by Kugel Rohr fractional distillation (150° C./0.05 mbar) to provide the title compound as a yellow oil (128 mg). | CCc1ccc(Br)cc1OC | null | 1.4 | null |
1,316,032 | ord_dataset-2d6edb8ffd434003bb508360153bd9bb | null | 2013-01-01T00:07:00 | true | [S:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]([OH:12])=O)=[CH:9][C:4]=2[N:3]=[N:2]1.O[N:14]=[C:15]([NH2:22])[C:16]1[CH:21]=[CH:20][CH:19]=[N:18][CH:17]=1.N>>[S:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3[O:12][N:22]=[C:15]([C:16]4[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=4)[N:14]=3)=[CH:9][C:4]=2[N:3]=[N:2]1 | NC(=NO)c1cccnc1 | O=C(O)c1ccc2snnc2c1 | null | N | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The title compound was prepared according to Method C using benzo[d][1,2,3]thiadiazole-5-carboxylic acid (Maybridge) and N′-hydroxynicotinimidamide (Tyger). 1H NMR (300 MHz, DMSO-d6) δ 7.69 (ddd, J=8.0, 4.9, 0.7 Hz, 1 H), 8.51 (dt, J=8.2, 1.9, 1.7 Hz, 1 H), 8.57 (dd, J=8.5, 1.7 Hz, 1 H), 8.73 (d, J=7.8 Hz, 1 H), 8.85 (dd, J=4.9, 1.5 Hz, 1 H), 9.32 (dd, J=2.4, 1.0 Hz, 1 H), 9.51 (dd, J=1.7, 0.7 Hz, 1 H) ppm; MS (DCI/NH3) m/z 282 (M+H)+. | c1cncc(-c2noc(-c3ccc4snnc4c3)n2)c1 | null | null | null |
960,952 | ord_dataset-ed65749688da45af8a8432967b017729 | null | 2010-01-01T00:05:00 | true | [P:1]([O:13][CH2:14][C:15]([CH3:27])([CH3:26])[CH2:16][CH2:17][O:18][Si](C(C)(C)C)(C)C)([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1.C(OCC)(=O)C>[P:1]([O:13][CH2:14][C:15]([CH3:27])([CH3:26])[CH2:16][CH2:17][OH:18])([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])([O:8][C:9]([CH3:10])([CH3:11])[CH3:12])=[O:2] | CC(C)(CCO[Si](C)(C)C(C)(C)C)COP(=O)(OC(C)(C)C)OC(C)(C)C | null | null | CCCC[N+](CCCC)(CCCC)CCCC | [F-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | CCOC(C)=O | null | null | null | null | null | null | null | null | null | 25 | 1 | To a solution of the product from Example 10B (0.435 g, 1.03 mmol) in THF (3.8 mL) was added a solution of tetrabutylammonium fluoride in THF (1 M, 1.2 mL), and the reaction was stirred at room temperature for 1 hour. The reaction mixture was diluted with ethyl acetate and washed with water and brine, dried over MgSO4, filtered and evaporated. The residue was purified by chromatography on silica gel, eluting with 33% ethyl acetate in hexane, to give the title compound (0.239 g, 75%). | CC(C)(CCO)COP(=O)(OC(C)(C)C)OC(C)(C)C | null | 74.8 | null |
985,575 | ord_dataset-35b56288528641309a040cc2b6710b61 | null | 2010-01-01T00:08:00 | true | [Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:41])[C:10]3([CH:15]([C:16]4[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:17]=4[O:23][C:24]([CH2:30][CH3:31])([C:27](O)=[O:28])[CH2:25][CH3:26])[CH2:14][C:13](=[O:32])[NH:12][CH:11]3[C:33]3[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:34]=3[CH3:40])[C:5]2=[CH:4][CH:3]=1.[NH:42]1[CH2:46][CH2:45][CH2:44][CH2:43]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.O>CN(C1C=CN=CC=1)C.CN(C=O)C>[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:41])[C:10]3([CH:15]([C:16]4[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:17]=4[O:23][C:24]([CH2:25][CH3:26])([C:27]([N:42]4[CH2:46][CH2:45][CH2:44][CH2:43]4)=[O:28])[CH2:30][CH3:31])[CH2:14][C:13](=[O:32])[NH:12][CH:11]3[C:33]3[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:34]=3[CH3:40])[C:5]2=[CH:4][CH:3]=1 | CCC(CC)(Oc1ccc(Cl)cc1C1CC(=O)NC(c2cc(F)ccc2C)C12C(=O)Nc1cc(Cl)ccc12)C(=O)O | C1CCNC1 | null | CN(C)C(On1nnc2cccnc21)=[N+](C)C | CN(C)c1ccncc1 | F[P-](F)(F)(F)(F)F | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | 5 | At room temperature, a mixture of racemic (2′S,3S,4′R)-6-chloro-4′-[5-chloro-2-(1-ethyl-1-hydroxycarbonyl-propoxy)-phenyl]-2′-(5-fluoro-2-methyl-phenyl)spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione (50 mg, 0.084 mmol), pyrrolidine (12 mg, 0.17 mmol), HATU (63.5 mg, 0.17 mmol) and DMAP (40.8 mg, 0.33 mmol) in DMF (2 mL) was stirred for 5 h. Then the mixture was poured into water and extracted with EtOAc thrice. The combined organic layers were washed with saturated NaCl solution twice, dried over anhydrous Na2SO4 and concentrated. The residue was purified by flash column to give the title compound as a white solid (30 mg). | CCC(CC)(Oc1ccc(Cl)cc1C1CC(=O)NC(c2cc(F)ccc2C)C12C(=O)Nc1cc(Cl)ccc12)C(=O)N1CCCC1 | null | 54.7 | null |
111,950 | ord_dataset-5237a168f9214b7ca3db5a1dc3e62d07 | null | 1983-01-01T00:12:00 | true | Cl.[NH2:2][C:3]1[CH:9]=[C:8]([S:10](=[O:13])(=[O:12])[NH2:11])[C:7]([Cl:14])=[CH:6][C:4]=1[NH2:5].[C:15](O)(=O)[CH3:16]>>[ClH:14].[Cl:14][C:7]1[C:8]([S:10](=[O:13])(=[O:12])[NH2:11])=[CH:9][C:3]2[NH:2][C:15]([CH3:16])=[N:5][C:4]=2[CH:6]=1 | Nc1cc(Cl)c(S(N)(=O)=O)cc1N | CC(=O)O | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | To 10 ml of 4 N hydrochloric acid containing 0.86 ml of acetic acid was added 2.22 g. of 2-amino-4-chloro-5-sulfamylaniline (VI) and the mixture refluxed for four hours. Concentration in vacuo gave a blue solid which was collected by filtration, dissolved in methanol, treated with charcoal and filtered. The blue solution was concentrated in vacuo and triturated with ether to yield a blue solid. Washing with methanol provided the product as light blue crystals which upon drying gave 1.0 g. of 5(6)-chloro-2-methyl-6(5)-sulfamyl-1(3)H-benzimidazole hydrochloride, m.p. 313°-316° C. | Cc1nc2cc(Cl)c(S(N)(=O)=O)cc2[nH]1 | null | null | null |
342,209 | ord_dataset-4c84bc8a34e1469aa1b156355c91cdcc | null | 1996-01-01T00:10:00 | true | Br[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][CH2:12][C:13]([O:15][CH3:16])=[O:14])=[CH:7][CH:6]=1)=[O:4].[N:17]1[CH:22]=[CH:21][C:20]([N:23]2[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)=[CH:19][CH:18]=1.CCOCC>C(#N)C>[N:17]1[CH:22]=[CH:21][C:20]([N:23]2[CH2:24][CH2:25][N:26]([CH2:2][C:3]([C:5]3[CH:10]=[CH:9][C:8]([CH2:11][CH2:12][C:13]([O:15][CH3:16])=[O:14])=[CH:7][CH:6]=3)=[O:4])[CH2:27][CH2:28]2)=[CH:19][CH:18]=1 | c1cc(N2CCNCC2)ccn1 | COC(=O)CCc1ccc(C(=O)CBr)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC#N | CCOCC | null | null | null | null | null | null | null | null | null | null | 8 | A solution of methyl 3-(4-bromoacetylphenyl)propionate (380 mg) in acetonitrile (4 ml) was added dropwise over 15 minutes to a stirred solution of 1-(4-pyridyl)piperazine (450 mg) in acetonitrile (10 ml) and the mixture stirred overnight. The mixture was then filtered and the filtrate concentrated in vacuo to give an oil. Purification by flash chromatography on silica eluting first with dichloromethane then 5% v/v methanol/dichloromethane gave a solid. Trituration with ether gave the title compound, 172 mg, as a solid: m.p. 141°-143° C.; NMR(d6DMSO) δ8.15(2H,d), 7.92(2H,d), 7.37(2H,d), 6.83(2H,d), 3.89(2H,s), 3.59(3H,s), 3.37(4H,t), 2.93(2H,t), 2.69(2H,t), 2.65(4H,t); m/e 368(M+H)+ ; calculated for C21H25N3O3. 0.25H2O: C, 67.8; H, 6.9; N, 11.3. found: C, 67.8; H, 6.9; N,11.1%. | COC(=O)CCc1ccc(C(=O)CN2CCN(c3ccncc3)CC2)cc1 | null | null | null |
740,158 | ord_dataset-437aa6654d5044ddaef3346dc4c6e08a | null | 2006-01-01T00:11:00 | true | Cl[C:2]1(Cl)[CH:6]2[N:7]([C:10]([O:12][CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[O:11])[CH2:8][CH2:9][CH:5]2[CH2:4][C:3]1=[O:20].[Cl-].[NH4+]>CO.[Zn]>[O:20]=[C:3]1[CH2:2][CH:6]2[N:7]([C:10]([O:12][CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[O:11])[CH2:8][CH2:9][CH:5]2[CH2:4]1 | O=C(OCc1ccccc1)N1CCC2CC(=O)C(Cl)(Cl)C21 | null | null | [Cl-] | [NH4+] | [Zn] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | 25 | 1 | Benzyl 6,6-dichloro-5-oxohexahydrocyclopenta[b]pyrrole-1(2H)-carboxylate (3.87 g, 11.8 mmol), prepared as described in Tetrahedron Lett. (1997), 38, 1869–1872, in MeOH (60 mL) at 0° C. was treated with solid ammonium chloride (6.32 g, 118 mmol) followed by zinc duct (Aldrich; 3.09 g, 47.2 mmol). After stirring at room temperature for 1 hour, the reaction mixture was filtered and the filtrate concentrated under reduced pressure. The residue was purified by chromatography (SiO2, 40% EtOAc/hexanes) to provide 2.57 g (84%) of the title compound. MS (DCI/NH3) m/z 260 (M+H)+. | O=C1CC2CCN(C(=O)OCc3ccccc3)C2C1 | null | 84 | null |
640,356 | ord_dataset-1c0bae7388cf460091d56129e95b3145 | null | 2004-01-01T00:06:00 | true | [CH2:1]([O:3][C:4](=[O:20])[CH2:5][S:6]([C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][C:17]#[C:18][CH3:19])=[CH:11][CH:10]=1)(=[O:8])=[O:7])[CH3:2].Cl.[N:22]1[CH:27]=[CH:26][CH:25]=[C:24]([CH2:28][N:29]([CH2:33][CH2:34]Cl)[CH2:30][CH2:31]Cl)[CH:23]=1>>[CH2:16]([O:15][C:12]1[CH:11]=[CH:10][C:9]([S:6]([C:5]2([C:4]([O:3][CH2:1][CH3:2])=[O:20])[CH2:34][CH2:33][N:29]([CH2:28][C:24]3[CH:23]=[N:22][CH:27]=[CH:26][CH:25]=3)[CH2:30][CH2:31]2)(=[O:7])=[O:8])=[CH:14][CH:13]=1)[C:17]#[C:18][CH3:19] | ClCCN(CCCl)Cc1cccnc1 | CC#CCOc1ccc(S(=O)(=O)CC(=O)OCC)cc1 | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Ethyl 4-{[4-(2-butynyloxy)phenyl]sulfonyl}-1-(3-pyridinylmethyl)-4-piperidine carboxylate was prepared according to the general method as outlined in example 1 (step 6), starting from (4-but-2-ynyloxy-benzenesulfonyl)-acetic acid ethyl ester (4 g, 16.9 mmol) and 3-pyridyl methyl [bis(2-chloroethyl)]amine hydrochloride (4.18 g, 18.6 mmol); 370 mg brown oil. Yield 5%; MS: 457.4 (M+H)+. | CC#CCOc1ccc(S(=O)(=O)C2(C(=O)OCC)CCN(Cc3cccnc3)CC2)cc1 | null | 5 | null |
1,149,853 | ord_dataset-b195433d5c354ddfb6cde0d53c41910f | null | 2012-01-01T00:04:00 | true | F[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[N+:9]([O-:11])=[O:10].C(O)C.[CH3:15][CH:16]([S-:18])[CH3:17].[Na+]>>[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([S:18][CH:16]([CH3:17])[CH3:15])[C:3]=1[N+:9]([O-:11])=[O:10] | O=[N+]([O-])c1c(F)cccc1F | CC(C)[S-] | null | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | null | null | null | null | null | null | null | null | null | null | 25 | 0.5 | 1,3-Difluoro-2-nitro-benzene (5.00 g, 31.4 mmol) was stirred in Ethanol (25 mL, 430 mmol) and treated with sodium 2-propanethiolate (3.08 g, 31.4 mmol) in several portions over 5 min. The reaction mixture was stirred at rt for 30 mins, was concentrated under reduced pressure, diluted with water, and extracted with CH2Cl2. The organic layer was dried over MgSO4, filtered, and concentrated under reduced pressure to afford a yellow oil. | CC(C)Sc1cccc(F)c1[N+](=O)[O-] | null | null | null |
923,407 | ord_dataset-cc0899cd744f4f7f8e7f2463560faad1 | null | 2009-01-01T00:12:00 | true | [C:1]1([S:7]([N:10]2[CH2:12][CH:11]2[C:13]([N:15]2[CH2:20][CH2:19][N:18]([C:21]3[CH:26]=[C:25]([CH3:27])[CH:24]=[CH:23][C:22]=3[CH3:28])[CH2:17][CH2:16]2)=[O:14])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[I-].[Na+].[CH2:31]([N:35]=[C:36]=[O:37])[CH2:32][CH2:33][CH3:34]>>[C:1]1([S:7]([N:10]2[CH2:12][CH:11]([C:13]([N:15]3[CH2:20][CH2:19][N:18]([C:21]4[CH:26]=[C:25]([CH3:27])[CH:24]=[CH:23][C:22]=4[CH3:28])[CH2:17][CH2:16]3)=[O:14])[N:35]([CH2:31][CH2:32][CH2:33][CH3:34])[C:36]2=[O:37])(=[O:8])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1 | Cc1ccc(C)c(N2CCN(C(=O)C3CN3S(=O)(=O)c3ccccc3)CC2)c1 | CCCCN=C=O | null | [I-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | In analogy to example 2, (RS)-(1-benzenesulfonyl-aziridin-2-yl)-[4-(2,5-dimethyl-phenyl)-piperazin-1-yl]-methanone (example 2, step 3) was reacted with sodium iodide and butyl isocyanate to give the title compound as a colorless solid. MS: 499.0 ([M+H]+) | CCCCN1C(=O)N(S(=O)(=O)c2ccccc2)CC1C(=O)N1CCN(c2cc(C)ccc2C)CC1 | null | null | null |
669,376 | ord_dataset-e90cd41afe844e49875435eb99903799 | null | 2005-01-01T00:05:00 | true | [CH:1]([C:4]1[C:13]2[C:8](=[CH:9][C:10]([O:17]C)=[C:11]([C:14](=[O:16])[CH3:15])[CH:12]=2)[O:7][C:6]([CH3:20])([CH3:19])[CH:5]=1)([CH3:3])[CH3:2].B(Br)(Br)Br>ClCCl>[OH:17][C:10]1[CH:9]=[C:8]2[C:13]([C:4]([CH:1]([CH3:2])[CH3:3])=[CH:5][C:6]([CH3:20])([CH3:19])[O:7]2)=[CH:12][C:11]=1[C:14](=[O:16])[CH3:15] | COc1cc2c(cc1C(C)=O)C(C(C)C)=CC(C)(C)O2 | null | null | BrB(Br)Br | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | null | null | As described in General Procedure J, a solution of 1-(4-isopropyl-7-methoxy-2,2-dimethyl-2H-chromen-6-yl)-ethanone (Compound 54, 752 mg, 2.43 mmol) in dichloromethane was treated with boron tribromide (1M in dichloromethane, 3.64 mL, 3.64 mmol) to afford the title compound as a bright yellow oil. | CC(=O)c1cc2c(cc1O)OC(C)(C)C=C2C(C)C | null | null | null |
682,926 | ord_dataset-359b8fc87f4244be89d6f02bc5036eac | null | 2005-01-01T00:09:00 | true | C(OC(=O)[NH:7][C:8]([CH3:46])([CH3:45])[CH2:9][CH:10]=[CH:11][C:12](=[O:44])[N:13]([CH:15]([C:27](=[O:43])[N:28]([CH:30]([C:39](=[O:42])[NH:40][CH3:41])[CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=1[F:38])[CH3:29])[CH2:16][C:17]1[CH:26]=[CH:25][C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:18]=1)[CH3:14])(C)(C)C.FC(F)(F)C(O)=O.C(=O)([O-])O.[Na+].C(=O)([O-])[O-].[Na+].[Na+].C(=O)([O-])O.[Na+]>C(Cl)Cl>[F:38][C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=1[CH2:31][CH:30]([N:28]([CH3:29])[C:27]([CH:15]([N:13]([CH3:14])[C:12](=[O:44])[CH:11]=[CH:10][CH2:9][C:8]([NH2:7])([CH3:46])[CH3:45])[CH2:16][C:17]1[CH:26]=[CH:25][C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:18]=1)=[O:43])[C:39](=[O:42])[NH:40][CH3:41] | CNC(=O)C(Cc1ccccc1F)N(C)C(=O)C(Cc1ccc2ccccc2c1)N(C)C(=O)C=CCC(C)(C)NC(=O)OC(C)(C)C | null | null | O=C([O-])O | O=C([O-])[O-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | O=C(O)C(F)(F)F | null | null | null | null | null | null | null | null | null | 25 | 0.08 | {4-[(1-{[2-(2-Fluorophenyl)-1-methylcarbamoylethyl]methylcarbamoyl}2-(2-naphthyl)ethyl)methylcarbamoyl]-1,1-dimethyl-but-3-enyl}carbamic acid tert-butyl ester (0.36 g; 0.557 mmol) was dissolved in methylene chloride (3 ml). Trifluoro acetic acid (3 ml) was added and the reaction mixture was stirred 5 min at room temperature. Methylene chloride (25 ml), sodium hydrogen carbonate/sodium carbonate (3 ml) and sodium hydrogen carbonate (s) was added until pH=8. The organic phase was dried (magnesium sulfate) and the solvent was removed in vacuo. The residue was lyophylised to afford 0.237 g of the title compound. | CNC(=O)C(Cc1ccccc1F)N(C)C(=O)C(Cc1ccc2ccccc2c1)N(C)C(=O)C=CCC(C)(C)N | null | 77.8 | null |
1,068,672 | ord_dataset-5df93261afc143c3ae919a57ff4fc1d4 | null | 2011-01-01T00:07:00 | true | [CH3:1][CH2:2][O:3][C:4]([C@@H:6]1[CH2:10][C@H:9]([C:11]([CH3:13])=[CH2:12])[C@H:8]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([O:22][CH2:23][CH2:24][CH2:25][O:26][CH3:27])[CH:15]=2)[N:7]1[C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])=[O:5]>C1(C)C=CC=CC=1.[Pd]>[CH3:1][CH2:2][O:3][C:4]([C@@H:6]1[CH2:10][C@@H:9]([CH:11]([CH3:13])[CH3:12])[C@H:8]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([O:22][CH2:23][CH2:24][CH2:25][O:26][CH3:27])[CH:15]=2)[N:7]1[C:28]([O:30][C:31]([CH3:34])([CH3:32])[CH3:33])=[O:29])=[O:5] | C=C(C)[C@H]1C[C@@H](C(=O)OCC)N(C(=O)OC(C)(C)C)[C@H]1c1ccc(OC)c(OCCCOC)c1 | null | null | [Pd] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Cc1ccccc1 | null | null | null | null | null | null | null | null | null | null | 25 | 2 | A solution of (2S,4R,5R)-4-Isopropenyl-5-[4-methoxy-3-(3-methoxy-propoxy)-phenyl]-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-ethyl ester VIIa (0.3 g) in 10 mL of toluene is treated with 50 mg of 5% palladium on carbon. The suspension is stirred under an atmosphere of hydrogen for 2 hours at room temperature and filtered. The solvent is removed in vacuum to give the desired compound as an oil. | CCOC(=O)[C@@H]1C[C@@H](C(C)C)[C@H](c2ccc(OC)c(OCCCOC)c2)N1C(=O)OC(C)(C)C | null | null | null |
939,397 | ord_dataset-90b0aa1f83334a02919b2be3a1c04542 | null | 2010-01-01T00:02:00 | true | [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9](=[O:11])[CH3:10].Cl.[C:13]([O:16][CH2:17][CH3:18])(=[O:15])[CH3:14]>O1CCCC1>[OH:11][C:9]([C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=1[O:2][CH3:1])([CH3:10])[CH2:14][C:13]([O:16][CH2:17][CH3:18])=[O:15] | CCOC(C)=O | COc1ccccc1C(C)=O | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | null | 4 | Under argon atmosphere, 20 mL (10.7 mmol, 2 equivalent) of the solution of ethyl bromozincacetate in tetrahydrofuran obtained in Example 43 was added dropwise to a solution of 0.74 mL (5.35 mmol) of o-methoxyacetophenone in 2.75 mL of THF at 7˜10° C. The mixture was stirred at to 4˜6° C. for 4 hours. 10 mL of 1N hydrochloric acid was added dropwise at 20° C. or lower, followed by dilution with 30 mL of ethyl acetate. Then, the layers were separated. The organic layer was washed successively with 5 mL (×2) of 1N hydrochloric acid, 5 mL of water, 5 mL (×2) of an aqueous saturated sodium bicarbonate solution, and 5 mL (×2) of an aqueous saturated sodium chloride solution. After washing, the organic layer was dried with anhydrous magnesium sulfate. Concentration under reduced pressure afforded 1.43 g of the desired product (NMR yield 96%; internal standard dioxane). | CCOC(=O)CC(C)(O)c1ccccc1OC | null | 96 | null |
633,690 | ord_dataset-de283386b8034acd99fba96d3c7d3227 | null | 2004-01-01T00:04:00 | true | [C:1](Cl)(=[O:5])[C:2](Cl)=O.[C:7]([O:11][C:12]([NH:14][CH2:15][CH:16]1[CH2:21][CH2:20][CH:19](C(O)=O)[CH2:18][CH2:17]1)=[O:13])([CH3:10])([CH3:9])[CH3:8].[N-]=[N+]=[N-].[Na+]>C1(C)C=CC=CC=1>[C:7]([O:11][C:12]([NH:14][CH2:15][CH:16]1[CH2:17][CH2:18][CH:19]([NH:14][C:12](=[O:11])[O:5][CH2:1][C:2]2[CH:20]=[CH:21][CH:16]=[CH:17][CH:18]=2)[CH2:20][CH2:21]1)=[O:13])([CH3:8])([CH3:9])[CH3:10] | CC(C)(C)OC(=O)NCC1CCC(C(=O)O)CC1 | O=C(Cl)C(=O)Cl | null | [N-]=[N+]=[N-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Cc1ccccc1 | null | null | null | null | null | null | null | null | null | null | 25 | 4 | Oxalyl chloride (1.1 equivalents) was added dropwise to a mixture of 4-[[(tert-butoxycarbonyl)-amino]methyl]-cyclohexanecarboxylic acid (1 equivalent, Maybridge) in toluene. The reaction mixture was stirred at room temperature for 2-6 h. The solvent was removed in vacuo, the residue was dissolved in acetone and the resulting mixture was added dropwise to an aqueous solution of sodium azide (1.2 equivalents) at a rate such as to maintain a temperature of 10-15° C. After the completion of the reaction, the reaction mixture was extracted with ethyl acetate, the combined extracts were dried and concentrated in vacuo. The residue was dissolved in acetone and added slowly to warm (60° C.) benzene. After the completion of the reaction, benzyl alcohol was added to the reaction mixture, stirred for 2 days and the desired product was isolated (For Typical References, See: G. Schroeter Ber. 1909, 42, 3356; and Allen, C. F. H.; Bell, A. Org. Syn. Coll. Vol. 3 (1955) 846.). | CC(C)(C)OC(=O)NCC1CCC(NC(=O)OCc2ccccc2)CC1 | null | null | null |
859,913 | ord_dataset-93908aaae836460ebd48d733eccad483 | null | 2009-01-01T00:01:00 | true | [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6](I)=[C:5]([O:10][CH3:11])[C:4]=1[O:12][CH3:13].C([Li])CCC.[CH3:19][N:20]([CH3:32])[C:21]1[CH:30]=[C:29]2[C:24]([C:25](=O)[CH2:26][CH2:27][O:28]2)=[CH:23][CH:22]=1>>[CH3:19][N:20]([CH3:32])[C:21]1[CH:30]=[C:29]2[C:24]([C:25]([C:7]3[CH:8]=[C:3]([O:2][CH3:1])[C:4]([O:12][CH3:13])=[C:5]([O:10][CH3:11])[CH:6]=3)=[CH:26][CH2:27][O:28]2)=[CH:23][CH:22]=1 | COc1ccc(I)c(OC)c1OC | CN(C)c1ccc2c(c1)OCCC2=O | null | [Li]CCCC | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Compounds of this invention having the Formulae I-IV can also be prepared as illustrated by examplary reactions in Scheme V. A phenyl propionitrile is prepared from the condensation of acrylonitrile and dimethylaminophenol. The nitrile was hydrolysed to the acid and the intermediate compound cyclized to yield 7-dimethylamino-chroman-4-one. Trimethoxyiodobenzene was lithiated with butyl lithium and treated with 7-dimethylamino-chroman-4-one to produce dimethyl-[4-(3,4,5-trimethoxy-phenyl)-2H-chromen-7-yl]-amine. Alternatively, 7-dimethylamino-chroman-4-one could be first treated with copper chloride, followed by the addition of lithio trimethoxybenzene, to produce [3-chloro-4-(3,4,5-trimethoxy-phenyl)-2H-chromen-7-yl]-dimethyl-amine. | COc1cc(C2=CCOc3cc(N(C)C)ccc32)cc(OC)c1OC | null | null | null |
1,628,090 | ord_dataset-f0794d5ded7a4d3fab45cc3d7a89ee3d | null | 2015-01-01T00:09:00 | true | [C:1]([N-:5][CH:6]=[CH:7][N-:8][C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:4])([CH3:3])[CH3:2].[Li+].[Li+].[Cl:15][SiH:16](Cl)Cl>CCCCCC>[Cl:15][SiH:16]1[N:5]([C:1]([CH3:3])([CH3:4])[CH3:2])[CH:6]=[CH:7][N:8]1[C:9]([CH3:12])([CH3:11])[CH3:10] | Cl[SiH](Cl)Cl | CC(C)(C)[N-]C=C[N-]C(C)(C)C | null | [Li+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCCCCC | null | null | null | null | null | null | null | null | null | null | 25 | 3 | In an argon atmosphere, a dilithium(N,N′-di-tert-butyl-1,2-vinylenediaminide) solution prepared according to the procedure and reagent quantities described in Reference Example-9 was added to a hexane (50 mL) solution containing 25.20 g (186.0 mmol) of trichlorosilane, and the mixture was stirred at room temperature for 3 hours. Insoluble matters produced were separated by filtration, and the solvent was removed by distillation from the filtrate under atmospheric pressure. The obtained residue was distilled under reduced pressure (distillation temperature: 80° C./3.8×102 Pa) to obtain 2-chloro-1,3-di-tert-butyl-1,3-diaza-2-silacyclopent-4-ene (Si(tBuNCHCHNtBu)(H)Cl) as a colorless liquid (yielded amount: 35.58 g, yield: 83%). | CC(C)(C)N1C=CN(C(C)(C)C)[SiH]1Cl | null | 83 | null |
438,912 | ord_dataset-3e8f24b5bc8e4d8bb9b6e7e89a956e12 | null | 1999-01-01T00:09:00 | true | [CH2:1]1[O:12][C:11]2[CH:10]=[CH:9][C:5]([CH2:6][CH2:7][NH2:8])=[CH:4][C:3]=2[O:2]1.[CH3:13][O:14][C:15](=[O:34])[C:16]1[CH:21]=[CH:20][C:19]([C:22]2[N:23]=[C:24](Cl)[C:25]3[C:30]([Cl:31])=[C:29]([CH3:32])[S:28][C:26]=3[N:27]=2)=[CH:18][CH:17]=1>>[CH3:13][O:14][C:15](=[O:34])[C:16]1[CH:21]=[CH:20][C:19]([C:22]2[N:23]=[C:24]([NH:8][CH2:7][CH2:6][C:5]3[CH:9]=[CH:10][C:11]4[O:12][CH2:1][O:2][C:3]=4[CH:4]=3)[C:25]3[C:30]([Cl:31])=[C:29]([CH3:32])[S:28][C:26]=3[N:27]=2)=[CH:18][CH:17]=1 | NCCc1ccc2c(c1)OCO2 | COC(=O)c1ccc(-c2nc(Cl)c3c(Cl)c(C)sc3n2)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The reaction procedure as above in wherein 3,4-methylenedioxyphenethylamine is reacted with 4-(4-chloro-5-chloro-6-methyl-thieno-[2,3-d]-pyrimidin-2-yl)-benzoic acid methylester yields 4-[4-(3,4-methylenedioxyphenethylamino)-5-chloro-6-methyl-thieno-[2,3-d]-pyrimidin-2-yl]-benzoic acid methylester. | COC(=O)c1ccc(-c2nc(NCCc3ccc4c(c3)OCO4)c3c(Cl)c(C)sc3n2)cc1 | null | null | null |
1,018,519 | ord_dataset-f024e9664ab64906a71a2ff6004cb3d0 | null | 2010-01-01T00:12:00 | true | C[O:2][C:3](=[O:21])[C:4]#[C:5][C:6]1[C:7]([NH:16][CH2:17][CH2:18][CH2:19][CH3:20])=[N:8][C:9]([C:12]([F:15])([F:14])[F:13])=[CH:10][CH:11]=1.[Li+].[OH-].Cl>C1COCC1>[CH2:17]([NH:16][C:7]1[C:6]([C:5]#[C:4][C:3]([OH:21])=[O:2])=[CH:11][CH:10]=[C:9]([C:12]([F:15])([F:13])[F:14])[N:8]=1)[CH2:18][CH2:19][CH3:20] | CCCCNc1nc(C(F)(F)F)ccc1C#CC(=O)OC | null | null | Cl | [Li+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | 25 | 3 | To a suspension of (2-butylamino-6-trifluoromethyl-pyridin-3-yl)-propynoic acid methyl ester (78 mg, 0.26 mmol) in THF (0.50 ml) was added a solution of 1 N-LiOH (1.0 ml), and the mixture was stirred for 3 hours at room temperature. The reaction mixture was acidified with 1N HCl to pH 1˜2. The solution was extracted three times with methylene chloride and then dried over anhyd. Na2SO4 and concentrated in vacuo to the title compound (50 mg, 65%). | CCCCNc1nc(C(F)(F)F)ccc1C#CC(=O)O | null | null | null |
1,092,207 | ord_dataset-52a37d876ddb453e86de0c15fa233d29 | null | 2011-01-01T00:09:00 | true | Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C@@H:11]([OH:13])[CH3:12])=[N:9][N:10]=2)[N:7]=1.[C:14]1(B(O)O)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C([O-])([O-])=O.[K+].[K+].O1CCOCC1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[C:14]1([C:2]2[CH:3]=[CH:4][C:5]3[N:6]([C:8]([C@@H:11]([OH:13])[CH3:12])=[N:9][N:10]=3)[N:7]=2)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1 | C[C@H](O)c1nnc2ccc(Cl)nn12 | OB(O)c1ccccc1 | null | c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1 | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1COCCO1 | O | null | null | null | null | null | null | null | null | null | 85 | null | A suspension of (1S)-1-(6-chloro[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethanol (0.289 mmol, 1 eq), phenylboronic acid (0.650 mmol, 2.3 eq), Pd(PPh3)4 (45.9 mg, 0.0397 mmol, 14 mol %), and K2CO3 (132.0 mg, 0.9551 mmol, 3.3 eq) in a 4:1 ratio of dioxane (4 mL) to H2O (1 mL) was evacuated and charged with nitrogen several times. The reaction sample was then heated conventionally at 85° C. for 1 h. CH2Cl2 and H2O were added and a standard aqueous workup was performed. The crude material was purified by pTLC [Silicycle, 1000 μM, 20×20 plate], which required two developments in a 3% MeOH in EtOAc solvent system. 1H NMR (400 MHz, CDCl3): δ=1.93 (d, J=6.6 Hz, 3H), 3.00 (br s, 1H), 5.64 (q, J=6.6 Hz, 1H), 7.53-7.61 (m, 3H), 7.66 (d, J=9.9 Hz, 1H), 7.95-8.01 (m, 2H), 8.25 (d, J=9.9 Hz, 1H). MS (ES+): m/z 241.08 (100) [MH+]. HPLC: tR=2.51 min (ZQ3, polar—5 min). | C[C@H](O)c1nnc2ccc(-c3ccccc3)nn12 | null | null | null |
771,897 | ord_dataset-8214eb8444a44dc2900ccb42dbeff15e | null | 2007-01-01T00:05:00 | true | [Cl:1][C:2]1[C:19]([Cl:20])=[CH:18][C:5]2[N:6]=[C:7]([C:9]3[CH:14]=[CH:13][C:12]([C:15](O)=[O:16])=[CH:11][CH:10]=3)[NH:8][C:4]=2[CH:3]=1.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH3:43][N:44]1[C:49]([CH3:51])([CH3:50])[CH2:48][CH:47]([NH2:52])[CH2:46][C:45]1([CH3:54])[CH3:53]>C1COCC1>[Cl:1][C:2]1[C:19]([Cl:20])=[CH:18][C:5]2[N:6]=[C:7]([C:9]3[CH:10]=[CH:11][C:12]([C:15]([NH:52][CH:47]4[CH2:46][C:45]([CH3:53])([CH3:54])[N:44]([CH3:43])[C:49]([CH3:51])([CH3:50])[CH2:48]4)=[O:16])=[CH:13][CH:14]=3)[NH:8][C:4]=2[CH:3]=1 | O=C(O)c1ccc(-c2nc3cc(Cl)c(Cl)cc3[nH]2)cc1 | CN1C(C)(C)CC(N)CC1(C)C | null | CCN=C=NCCCN(C)C | Cl | On1nnc2ccccc21 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | 25 | null | A mixture of 5,6-dichloro-2-(4-carboxyphenyl)benzimidazole (0.3 g, 0.9 mmol) prepared as described in Preparation 8, 1-hydroxybenzotriazole (0.145 g, 1.08 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.207 g, 1.08 mmol) in THF (10 ml) was heated at 35–40° C. for 1 h. 1,2,2,6,6,-Pentamethyl-4-aminopiperidine in THF (2 ml) was added dropwise and the reaction was refluxed for 1 h. After cooling to room temperature, the solvent was removed under reduced pressure and the residue was treated with 2N NaOH (5 ml). The solid was filtered, washed with water and dried at 50° C. under vacuum. The solid was suspended in isopropyl alcohol and stirred for half an hour, filtered and dried to give 91 mg of the title compound (yield 22%) as an yellow powder, mp>280° C. | CN1C(C)(C)CC(NC(=O)c2ccc(-c3nc4cc(Cl)c(Cl)cc4[nH]3)cc2)CC1(C)C | null | 22 | null |
922,123 | ord_dataset-8e59bd24817446f7b1c68e805b8e5f1d | null | 2009-01-01T00:11:00 | true | [CH3:1][N:2]1[C:10]2[C@@:9]3([CH3:14])[C:11]([CH3:13])([CH3:12])[C@H:6]([CH2:7][CH2:8]3)[C:5]=2[C:4](=[O:15])[NH:3]1.[CH3:16][O:17][C:18]([C:20]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][CH:21]=1)=[O:19]>ClCCl.N1C=CC=CC=1.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH3:16][O:17][C:18](=[O:19])[C:20]1[CH:25]=[CH:24][C:23]([N:3]2[C:4](=[O:15])[C:5]3[C@@H:6]4[C:11]([CH3:12])([CH3:13])[C@@:9]([CH3:14])([CH2:8][CH2:7]4)[C:10]=3[N:2]2[CH3:1])=[CH:22][CH:21]=1 | COC(=O)c1ccc(B(O)O)cc1 | Cn1[nH]c(=O)c2c1[C@]1(C)CC[C@H]2C1(C)C | null | [Cu+2] | CC(=O)[O-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | c1ccncc1 | ClCCl | null | null | null | null | null | null | null | null | null | 25 | 48 | A mixture of (4S,7R)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 19; 100 mg, 0.48 mmol), 4-methoxycarbonyl-phenyl-boronic acid (180 mg, 0.97 mmol), and copper(II) acetate (133 mg, 0.73 mmol) in dichloromethane (1 mL) and pyridine (0.8 mL) was stirred at room temperature for 2 days. The reaction mixture was evaporated and purified using an Analogix Intelliflash 280 system (Analogix, Inc., Burlington, Wis.) with an Isco 12 g column, eluting with 10-60% ethyl acetate/hexanes to give 4-((4S,7R)-1,7,8,8-tetramethyl-3-oxo-1,3,4,5,6,7-hexahydro-4,7-methano-indazol-2-yl)-benzoic acid methyl ester (48.2 mg, 29%) as an off-white solid. ES(+)-MS (M+H) 341. | COC(=O)c1ccc(-n2c(=O)c3c(n2C)[C@]2(C)CC[C@H]3C2(C)C)cc1 | null | 29.5 | null |
805,428 | ord_dataset-ed846b4b229e4bb09ad9dba95ad7ebeb | null | 2008-01-01T00:01:00 | true | [CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([CH2:9][C:10]2[C:19]3[N:18]=[CH:17][CH:16]=[CH:15][C:14]=3[C:13](=O)[NH:12][CH:11]=2)=[CH:5][CH:4]=1.P(Cl)(Cl)([Cl:23])=O.Cl>C(#N)C.O1CCOCC1>[Cl:23][C:13]1[N:12]=[CH:11][C:10]([CH2:9][C:6]2[CH:7]=[N:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)=[C:19]2[C:14]=1[CH:15]=[CH:16][CH:17]=[N:18]2 | COc1ccc(Cc2c[nH]c(=O)c3cccnc23)cn1 | O=P(Cl)(Cl)Cl | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1COCCO1 | CC#N | null | null | null | null | null | null | null | null | null | 25 | null | 396 mg (1.48 mmol) of 8-[(6-methoxy-pyridin-3-yl)-methyl]-6H-[1,6]naphthyridin-5-one in 24 ml of acetonitrile are mixed, whilst excluding air, with 1.4 ml (15 mmol) of phosphorus oxychloride and 0.78 ml of 4 N HCl in dioxan and stirred for 96 h at 65° C. After cooling to RT, partial concentration by evaporation takes place on a RE, then 40 ml of ice water and 10 ml of NH3 solution are added and extraction carried out 3 times with EtOAc. The organic phases are washed with water and brine, dried (Na2SO4) and concentrated by evaporation to form 5-chloro-8-[(6-methoxy-pyridin-3-yl)-methyl]-[1,6]naphthyridine (contaminated with a little 5-chloro-8-[(6-chloro-pyridin-3-yl)-methyl]-[1,6]naphthyridine); FAB-MS: (M+H)+=286; HPLC(gradients20-100) tRef=10.2. | COc1ccc(Cc2cnc(Cl)c3cccnc23)cn1 | null | null | null |
1,309,189 | ord_dataset-78c3f723155a4347a902b53bcee1524d | null | 2013-01-01T00:06:00 | true | [C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:13][CH2:12][C:11]([C:17]([OH:20])([CH3:19])[CH3:18])([C:14]([OH:16])=O)[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:21][C:22]([F:36])([F:35])[C:23]1[CH:28]=[CH:27][N:26]=[C:25]([N:29]2[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)[CH:24]=1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>C(Cl)Cl>[OH:20][C:17]([C:11]1([C:14]([N:32]2[CH2:33][CH2:34][N:29]([C:25]3[CH:24]=[C:23]([C:22]([F:36])([F:21])[F:35])[CH:28]=[CH:27][N:26]=3)[CH2:30][CH2:31]2)=[O:16])[CH2:12][CH2:13][CH:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH2:10]1)([CH3:19])[CH3:18] | CC(C)(C)OC(=O)N[C@H]1CCC(C(=O)O)(C(C)(C)O)C1 | FC(F)(F)c1ccnc(N2CCNCC2)c1 | null | CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C | F[P-](F)(F)(F)(F)F | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | CCN(CC)CC | null | null | null | null | null | null | null | null | null | 25 | 8 | To a suspension of (3S)-3-[(tert-butoxycarbonyl)amino]-1-(1-hydroxy-1-methylethyl)cyclopentanecarboxylic acid (150 mg, 0.52 mmol) and 1-[4-(trifluoromethyl)pyridin-2-yl]piperazine (130 mg, 0.57 mmol) in methylene chloride (3 mL) under N2 was added triethylamine (0.16 g, 1.6 mol) and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (0.25 g, 0.57 mmol). After being stirred at room temperature overnight, the reaction was quenched by saturated NaHCO3 solution and extracted with methylene chloride three times. The combined extracts were dried (MgSO4), filtered, concentrated and purified by flash column chromatography to yield the desired product (76 mg, 29%). | CC(C)(C)OC(=O)NC1CCC(C(=O)N2CCN(c3cc(C(F)(F)F)ccn3)CC2)(C(C)(C)O)C1 | null | 29.2 | null |
2,503 | ord_dataset-a0bc986c3cf848c2a1ea93b297d1ad89 | null | 1976-01-01T00:02:00 | true | [CH3:1][C:2]([CH2:6][CH2:7][CH:8]=[C:9]([CH3:47])[CH2:10][CH2:11][CH:12]=[C:13]([CH3:46])[CH2:14][CH2:15][CH:16]=[C:17]([CH3:45])[CH2:18][CH2:19][CH:20]=[C:21]([CH3:44])[CH2:22][CH2:23][C:24](=[O:43])[CH:25]([CH3:42])[CH2:26][CH2:27][CH:28]=[C:29]([CH3:41])[CH2:30][CH2:31][CH:32]=[C:33]([CH3:40])[CH2:34][CH2:35][CH:36]=[C:37]([CH3:39])[CH3:38])=[CH:3][CH2:4][OH:5].[CH3:48][C:49](OCC1C2C(=CC=CC=2)C(COC(C)=O)=C2C=1C=CC=C2)=[O:50].CCOCC>N1C=CC=CC=1>[C:49]([O:5][CH2:4][CH:3]=[C:2]([CH3:1])[CH2:6][CH2:7][CH:8]=[C:9]([CH3:47])[CH2:10][CH2:11][CH:12]=[C:13]([CH3:46])[CH2:14][CH2:15][CH:16]=[C:17]([CH3:45])[CH2:18][CH2:19][CH:20]=[C:21]([CH3:44])[CH2:22][CH2:23][C:24](=[O:43])[CH:25]([CH3:42])[CH2:26][CH2:27][CH:28]=[C:29]([CH3:41])[CH2:30][CH2:31][CH:32]=[C:33]([CH3:40])[CH2:34][CH2:35][CH:36]=[C:37]([CH3:39])[CH3:38])(=[O:50])[CH3:48] | CC(C)=CCCC(C)=CCCC(C)=CCCC(C)C(=O)CCC(C)=CCCC(C)=CCCC(C)=CCCC(C)=CCCC(C)=CCO | CC(=O)OCc1c2ccccc2c(COC(C)=O)c2ccccc12 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOCC | c1ccncc1 | null | null | null | null | null | null | null | null | null | 0 | 5 | To a solution of 3,7,11,15,19,23,27,31,35-nonamethyl-2,6,10,14,18,26,30,34-hexatriacontaoctaen-22-on-1-ol 6.5 g) in pyridine (1 g), acetic anhdyride (3.0 g) is added, and the resulting mixture is allowed to stand at room temperature for 5 hours. The reaction mixture is poured into ice water and shaken with ether. The ether layer is washed with water, dried and evaporated. The residual material (6.5 g) is chromatographed on silica gel (70 g) using benzene to give 1-acetoxy-3,7,11,15,19,23,27,31,35-nonamethyl-2,6,10,14,18,26,30,34-hexatriacontaoctaen-22-one (6.1 g). A solution of this compound in ethanol (6 ml) is dropwise added to a solution of sodium borohydride (0.1 g) in ethanol (10 ml) while cooling with ice, and stirring is continued for 3 hours. The reaction mixture is poured into an aqueous saturated solution of ammonium chloride and extracted with ether. The ether extract is washed with water, dried and concentrated. The residual material (4.8 g) is treated as in Example 1 (5) a) to give 1-acetoxy-3,7,11,15,19,23,27,31, 35-nonamethyl-2,6,10,14,18,26,30,34-hexatriacontaoctaen- 22-ol (2.1 g) as a fraction (1) and 3,7,11,15,19,23,27,31,35-nonamethyl-2,6,10,14,18,26,30,34-hexatriacontaoctaene-1,22-diol (0.9 g) as a fraction (2). The latter is treated with acetic anhydride as above to give 1-acetoxy-3,7,11,15,19,23,27,31,35-nonamethyl-2,6,10,14,18,26,30,34-hexatriacontaoctaen-22-ol (0.82 g). | CC(=O)OCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC(=O)C(C)CCC=C(C)CCC=C(C)CCC=C(C)C | null | null | null |
250,732 | ord_dataset-41ea179beba54bed8cd874a5ec3469f7 | null | 1992-01-01T00:07:00 | true | [OH:1][CH:2]([CH:41]1[CH2:45][O:44]C(C)(C)[O:42]1)[CH2:3][NH:4][C:5](=[O:40])[C:6]1[CH:24]=[C:23]([S:25](=[O:39])(=[O:38])[NH:26][C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][C:28]=2[C:34]([F:37])([F:36])[F:35])[CH:22]=[C:8]([C:9]([NH:11][CH2:12][CH:13]([OH:21])[CH:14]2[CH2:18][O:17]C(C)(C)[O:15]2)=[O:10])[CH:7]=1.Cl>C(O)C.O>[OH:1][CH:2]([CH:41]([OH:42])[CH2:45][OH:44])[CH2:3][NH:4][C:5](=[O:40])[C:6]1[CH:24]=[C:23]([S:25](=[O:38])(=[O:39])[NH:26][C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][C:28]=2[C:34]([F:37])([F:35])[F:36])[CH:22]=[C:8]([C:9]([NH:11][CH2:12][CH:13]([OH:21])[CH:14]([OH:15])[CH2:18][OH:17])=[O:10])[CH:7]=1 | CC1(C)OCC(C(O)CNC(=O)c2cc(C(=O)NCC(O)C3COC(C)(C)O3)cc(S(=O)(=O)Nc3ccc(F)cc3C(F)(F)F)c2)O1 | null | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CCO | null | null | null | null | null | null | null | null | null | 60 | 4 | 3.79 g (5.46 mmol) of 5-[N-(4-fluoro-2-trifluoromethylphenyl)sulfamoyl]-isophthalic acid-bis[2-hydroxy-2-(2,2-dimethyl-1,3-dioxolan-4-yl)-ethylamide] is dissolved in a mixture of 40 ml of ethanol and 10 ml of water and the solution is acidified with dilute hydrochloric acid to pH 1. It is stirred at this pH for 4 hours at 60° C. The solution is then adjusted to pH 6.1 with the anion exchanger Amberlite IRA 67, filtered and evaporated to dryness in a vacuum. The solid amorphous residue is dried in a vacuum at 50° C. 2.55 g (4.16 mmol) =76.12% of the theoretical yield is obtained as an amorphous solid. | O=C(NCC(O)C(O)CO)c1cc(C(=O)NCC(O)C(O)CO)cc(S(=O)(=O)Nc2ccc(F)cc2C(F)(F)F)c1 | null | null | null |
1,700,124 | ord_dataset-54347fcace774f89850681d6dec8009f | null | 2016-01-01T00:03:00 | true | [C:1]([C:5]1[CH:6]=[C:7]([C:15]2[CH:23]=[CH:22][CH:21]=[C:20]3[C:16]=2[CH:17]=[CH:18][CH2:19]3)[CH:8]=[C:9]([C:11]([CH3:14])([CH3:13])[CH3:12])[CH:10]=1)([CH3:4])([CH3:3])[CH3:2].CS(C)=O.[Br:28]N1C(=O)CCC1=O.C1(C)C=CC(S(O)(=O)=O)=CC=1>O>[Br:28][C:18]1[CH2:19][C:20]2[C:16]([CH:17]=1)=[C:15]([C:7]1[CH:8]=[C:9]([C:11]([CH3:14])([CH3:13])[CH3:12])[CH:10]=[C:5]([C:1]([CH3:2])([CH3:3])[CH3:4])[CH:6]=1)[CH:23]=[CH:22][CH:21]=2 | CC(C)(C)c1cc(-c2cccc3c2C=CC3)cc(C(C)(C)C)c1 | O=C1CCC(=O)N1Br | null | Cc1ccc(S(=O)(=O)O)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CS(C)=O | O | null | null | null | null | null | null | null | null | null | 25 | 8 | A cold solution (5° C.) of compound 5 (49 g, 161 mmol, 1 equiv), dimethyl sulfoxide (500 mL) and water (5 mL) was treated in one portion with N-bromosuccinimide (43 g, 241 mmol, 1.5 equiv). The bath was removed and the reaction allowed to stir at room temperature overnight. The reaction was poured into water (1 L) and the mixture extracted with ethyl acetate (2×500 mL). The combined organic layers were washed with saturated brine (1 L), dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was dissolved in toluene (500 mL) and p-toluenesulfonic acid (6.2 g, 32.6 mmol, 0.2 equiv) was added. The mixture was refluxed for 20 hours while removing water with a Dean-Stark trap. The reaction was cooled to room temperature and concentrated under reduced pressure. The resulting residue was purified over silica gel (1 Kg) eluting with heptanes to give compound 6 (41 g, 66% yield) as a white solid. | CC(C)(C)c1cc(-c2cccc3c2C=C(Br)C3)cc(C(C)(C)C)c1 | null | 66.4 | null |
1,375,035 | ord_dataset-d23f2f15886d4c22b7d7ba5f0e203e81 | null | 2013-01-01T00:12:00 | true | O1CCCCC1[N:7]1[C:15]2[C:10](=[CH:11][C:12]([NH:16][C@H:17]3[CH2:22][CH2:21][CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18]3)=[CH:13][CH:14]=2)[CH:9]=[N:8]1.[ClH:30].O1CCOCC1>C(O)C>[ClH:30].[ClH:30].[NH:19]1[CH2:20][CH2:21][CH2:22][C@H:17]([NH:16][C:12]2[CH:11]=[C:10]3[C:15](=[CH:14][CH:13]=2)[NH:7][N:8]=[CH:9]3)[CH2:18]1 | CC(C)(C)OC(=O)N1CCC[C@H](Nc2ccc3c(cnn3C3CCCCO3)c2)C1 | null | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | C1COCCO1 | null | null | null | null | null | null | null | null | null | 25 | 2 | A 1 L round bottom flask was charged with (3S)-tert-butyl 3-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-ylamino)piperidine-1-carboxylate (32.4 g, 0.0809 mol, 1.00 eq) and EtOH (500 mL). To the ethanol solution was added 4N HCl in dioxane (40.0 mL, 0.160 mol, 2.0 eq), and the solution was stirred at room temperature for 2 h, giving an inhomogeneous dark brown solution. The solution was then heated to 75° C. with a mechanical stirrer and maintained at that temperature for 2 h, after which it was cooled to room temperature. A large amount of fine white solid was observed to form and was collected by filtration, and the filter cake was washed with isopropyl acetate (500 mL). The solid was dried in a vacuum oven at 45° C. for 3 days to give the title compound as an off-white powder (18.1 g, 77%). | c1cc2[nH]ncc2cc1N[C@H]1CCCNC1 | null | 77 | null |
920,506 | ord_dataset-8e59bd24817446f7b1c68e805b8e5f1d | null | 2009-01-01T00:11:00 | true | [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[C:20](=[O:21])[C:19]3[C:14](=[CH:15][C:16]([O:22][CH2:23][CH:24]4[CH2:26][O:25]4)=[CH:17][CH:18]=3)[O:13][CH:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[NH:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1>C(O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[C:20](=[O:21])[C:19]3[C:14](=[CH:15][C:16]([O:22][CH2:23][CH:24]([OH:25])[CH2:26][N:27]4[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]4)=[CH:17][CH:18]=3)[O:13][CH:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10] | C1CNCCN1 | COc1ccc(-c2coc3cc(OCC4CO4)ccc3c2=O)cc1OC | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | null | null | null | null | null | null | null | null | null | null | null | null | A mixture of compound 4 (obtained from example 2) (0.35 g, 1 mmol), piperazine (0.43 g, 5 mmol), and ethanol (30 mL) was refluxed for 6 hrs (TLC monitoring). After removal of solvent in vaccuo, the residue was treated with H2O (50 mL). The resulting precipitate was collected and purified by column chromatography (MeOH/CH2Cl2=1:25) to give the title compound 6b (0.25 g, 56% yield). M.p.: 84-85° C. | COc1ccc(-c2coc3cc(OCC(O)CN4CCNCC4)ccc3c2=O)cc1OC | null | 56.8 | null |
489,117 | ord_dataset-37b0416f244344a08cf357e851eedf2a | null | 2001-01-01T00:01:00 | true | [CH3:1][C:2]1([CH2:15][N:16]2[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]2)[CH2:6][C:5]2[C:7]([CH3:14])=[C:8]([NH2:13])[C:9]([CH3:12])=[C:10]([CH3:11])[C:4]=2[O:3]1.[C:22]1([CH2:28][CH2:29][C:30](O)=[O:31])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>>[CH3:1][C:2]1([CH2:15][N:16]2[CH2:21][CH2:20][N:19]([C:30](=[O:31])[CH2:29][CH2:28][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH2:18][CH2:17]2)[CH2:6][C:5]2[C:7]([CH3:14])=[C:8]([NH2:13])[C:9]([CH3:12])=[C:10]([CH3:11])[C:4]=2[O:3]1 | O=C(O)CCc1ccccc1 | Cc1c(C)c2c(c(C)c1N)CC(C)(CN1CCNCC1)O2 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Using 2,3-dihydro-2,4,6,7-tetramethyl-2-[(1-piperazinyl)methyl]-5-benzofuranamine and 3-phenylpropionic acid, the procedure of Example 10 was otherwise repeated to provide the title compound. Yield 73%. | Cc1c(C)c2c(c(C)c1N)CC(C)(CN1CCN(C(=O)CCc3ccccc3)CC1)O2 | null | 73 | null |
1,265,213 | ord_dataset-d3580a12b15e46cc91aa73f4f1a4a8cc | null | 2013-01-01T00:03:00 | true | [C:1]([C:4]1[CH:5]=[C:6]([NH:10][C:11](=[O:16])[C:12]([CH3:15])([CH3:14])[CH3:13])[CH:7]=[CH:8][CH:9]=1)(=[O:3])[CH3:2].[Br-:17].[Br-].[Br-].[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1>Br.CC(O)=O>[Br:17][CH2:2][C:1]([C:4]1[CH:5]=[C:6]([NH:10][C:11](=[O:16])[C:12]([CH3:15])([CH3:14])[CH3:13])[CH:7]=[CH:8][CH:9]=1)=[O:3] | [Br-] | CC(=O)c1cccc(NC(=O)C(C)(C)C)c1 | null | Br | c1cc[nH+]cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(=O)O | null | null | null | null | null | null | null | null | null | null | 25 | 24 | To a stirred solution of N-(3acetylphenyl)pivalamide 8z (0.30 g, 1.37 mmol) in 33% HBr in HOAc (5 mL) was added pyridinium tribromide (0.48 g, 1.51 mmol) and the mixture was stirred at room temperature for 24 h then poured into ice-cold water. The organic layer was extracted with DCM, washed with sat. aq. NaHCO3 and brine, dried over anhydrous MgSO4, and filtered. Evaporation of the solvent afforded 9z (0.32 g, 78%) which was used in the next step without further purification. 1H NMR (600 MHz, CDCl3): δ 8.08 (t, J=1.8 Hz, 1H), 7.94 (br s, 1H), 7.82 (dt, J=8.4, 1.2 Hz, 1H), 7.60 (dd, J=7.2 Hz, 1.2 Hz, 1H), 7.32 (t, J=7.8 Hz, 1H), 4.30 (s, 2H), 1.27 (s, 9H). 13C NMR (150 MHz, CDCl3): δ 191.2, 177.3, 139.0, 134.4, 129.3, 125.8, 124.4, 120.4, 39.7, 31.4, 27.5. MS m/z (ESI) 298.06 [M+H]+, 300.02 [(M+2)+H]+. | CC(C)(C)C(=O)Nc1cccc(C(=O)CBr)c1 | null | 78.3 | null |
734,225 | ord_dataset-76dd1b78ee414d2da0ed30700ef026f7 | null | 2006-01-01T00:10:00 | true | Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[NH:8]1[CH2:14][CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1>O>[N:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[N:8]1[CH2:14][CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1 | Brc1ccccn1 | C1CNCCNC1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | null | null | null | null | null | null | null | null | null | null | 100 | null | A mixture of 2-bromopyridine and 12 g of homopiperazine is heated at 100° C. for 6 hours. 50 ml of water are added to the reaction mixture and the resulting mixture is extracted with EtOAc, the organic phase is washed with saturated NaCl solution and dried over Na2SO4, and the solvent is evaporated off under vacuum. 1.28 g of the expected product are obtained. | c1ccc(N2CCCNCC2)nc1 | null | null | null |
250,413 | ord_dataset-41ea179beba54bed8cd874a5ec3469f7 | null | 1992-01-01T00:07:00 | true | [C:1]1([NH2:8])[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH2:7].C(N(CC)CC)C.[C:16](Cl)(=O)[CH2:17][CH2:18][CH2:19][CH2:20][CH3:21]>C(Cl)Cl>[CH2:17]([C:16]1[NH:7][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=2[N:8]=1)[CH2:18][CH2:19][CH2:20][CH3:21] | CCCCCC(=O)Cl | Nc1ccccc1N | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | CCN(CC)CC | null | null | null | null | null | null | null | null | null | null | null | To a solution of 0-phenylenediamine (2.2 g) and triethylamine (2.0 g) in methylene chloride (20 ml) was added dropwise caproyl chloride (2.3 g) with stirring under ice-cooling. The mixture was stirred for 3 hours at room temperature, washed with a saturated aqueous sodium bicarbonate and water, then dried. The solvent was evaporated. To the residue was added 3N-HCl, and the mixture was heated for 1.5 hour under reflux. The reaction mixture was made basic with 6N NaOH. Then precipitating crystals were recrystallized from ethyl acetate-hexane to give colorless needles (1.5 g, 47%), m.p. 161°-162° C. | CCCCCc1nc2ccccc2[nH]1 | null | 46.6 | null |
1,184,728 | ord_dataset-9cd817a75dfc4fe7ad19d4232772d5ff | null | 2012-01-01T00:07:00 | true | [NH2:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1I.O=[C:12]([CH3:16])[C:13]([OH:15])=[O:14].C1N2CCN(CC2)C1>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:6]([C:5]1[CH:4]=[C:3]2[C:2](=[CH:9][CH:8]=1)[NH:1][C:12]([C:13]([OH:15])=[O:14])=[CH:16]2)#[N:7] | N#Cc1ccc(N)c(I)c1 | CC(=O)C(=O)O | null | [Pd+2] | C1CN2CCN1CC2 | CC(=O)[O-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | 105 | 1 | A suspension of 4-amino-3-iodobenzonitrile (2.44 g), 2-oxopropanoic acid (2.64 g), DABCO (3.36 g), and Pd(OAc)2 in DMF (30 mL) was heated to 105° C. and stirred at that temperature for 1 hour. The solvent was evaporated. EtOAc (200 mL) was added and the resulting solution was washed with water (100 mL) and aqueous NaOH solution (20 mL). The combined aqueous solution was extracted with EtOAc (3×150 mL). The organic fractions were combined. The combined solution was dried over anhydrous magnesium sulfate. The dried solution was concentrated. The residue was triturated to afford 5-cyano-1H-indole-2-carboxylic acid (D20) (1.1 g) as a brown solid. | N#Cc1ccc2[nH]c(C(=O)O)cc2c1 | null | 59.1 | null |
1,473,176 | ord_dataset-fd1fa959d6264608b0b7fcda16741bfd | null | 2014-01-01T00:08:00 | true | [NH2:1][C@H:2]([C:4]1[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=1)[CH3:3].Cl[CH2:15][CH2:16][CH2:17][S:18](Cl)(=[O:20])=[O:19]>>[O:19]=[S:18]1(=[O:20])[CH2:17][CH2:16][CH2:15][N:1]1[C@H:2]([C:4]1[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=1)[CH3:3] | COC(=O)c1ccc([C@H](C)N)cc1 | O=S(=O)(Cl)CCCCl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Using methyl (S)-4-(1-aminoethyl)benzoate (0.61 g) and 3-chloropropane-1-sulfonyl chloride (0.54 mL) and by the reaction and treatment in the same manner as in Preparation Example 17, the title compound (0.90 g) was obtained. | COC(=O)c1ccc([C@H](C)N2CCCS2(=O)=O)cc1 | null | null | null |
940,025 | ord_dataset-90b0aa1f83334a02919b2be3a1c04542 | null | 2010-01-01T00:02:00 | true | C[O:2][C:3](=[O:30])[CH2:4][C:5]1[C:13]2[C:8](=[N:9][CH:10]=[CH:11][CH:12]=2)[N:7]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([S:21]([CH3:24])(=[O:23])=[O:22])=[CH:17][C:16]=2[C:25]([F:28])([F:27])[F:26])[C:6]=1[CH3:29].C1COCC1.[OH-].[Na+]>O>[CH3:24][S:21]([C:18]1[CH:19]=[CH:20][C:15]([CH2:14][N:7]2[C:8]3=[N:9][CH:10]=[CH:11][CH:12]=[C:13]3[C:5]([CH2:4][C:3]([OH:30])=[O:2])=[C:6]2[CH3:29])=[C:16]([C:25]([F:28])([F:27])[F:26])[CH:17]=1)(=[O:22])=[O:23] | COC(=O)Cc1c(C)n(Cc2ccc(S(C)(=O)=O)cc2C(F)(F)F)c2ncccc12 | null | null | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | 8 | To a mixture comprising [1-(4-methanesulfonyl-2-trifluoromethyl-benzyl)-2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl]-acetic acid methyl ester: (11.8 g, 26.8 mmol) in water (100 ml) and THF (250 ml) is added dropwise NaOH (53.6 ml of a 1M aqueous solution) at room temperature and the two phase suspension is allowed to stir overnight. The solvent is removed in vacuo and the crude is triturated with diethyl ether, DCM and ethyl acetate. The resulting solid is dissolved in hot water (150 ml) and adjusted to pH 3-4 using 6M HCl. The suspension that forms is filtered and is further purified by dissolving in hot IPA (250 ml) and refluxing in the presence of charcoal for 5 minutes. The solution is filtered and the titled product is recrystallised from water/IPA as a white/pale green crystals. (MH+ 427) | Cc1c(CC(=O)O)c2cccnc2n1Cc1ccc(S(C)(=O)=O)cc1C(F)(F)F | null | null | null |
1,356,896 | ord_dataset-d932d1d683704a8bad3d064bcb197acc | null | 2013-01-01T00:11:00 | true | [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([O:7][C:8]#[C:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:2]=1.N1C=CC(COC2C=CC(C=O)=CC=2)=C[CH:17]=1>>[N:1]1[CH:2]=[CH:17][C:4]([CH2:3][O:7][C:8]#[C:9][C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[CH:5][CH:6]=1 | O=Cc1ccc(OCc2ccncc2)cc1 | C(#Cc1ccccc1)Oc1cccnc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Prepared as for 4-(pyridine-3-yloxy)ethynylbenzene, using 4-(pyridine-4-ylmethoxy)benzaldehyde. | C(#Cc1ccccc1)OCc1ccncc1 | null | null | null |
172,048 | ord_dataset-7860c6f563014da8948ede63b7110bde | null | 1988-01-01T00:05:00 | true | [BH4-].[Na+].[CH2:3]([CH:12]([CH2:25][C:26]1[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=1)[N:13]1[CH:16]([O:17][C:18](=[O:20])[CH3:19])[CH:15]([C:21](=[O:23])[CH3:22])[C:14]1=[O:24])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[CH:6][CH:5]=1>C(O)(C)C.O>[CH2:25]([CH:12]([CH2:3][C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[CH:6][CH:5]=1)[N:13]1[CH:16]([O:17][C:18](=[O:20])[CH3:19])[CH:15]([CH:21]([OH:23])[CH3:22])[C:14]1=[O:24])[C:26]1[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=1 | COc1ccc(CC(Cc2ccc(OC)cc2)N2C(=O)C(C(C)=O)C2OC(C)=O)cc1 | null | null | [BH4-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CC(C)O | null | null | null | null | null | null | null | null | null | 25 | 0.5 | A mixture of sodium borohydride (38 mg) and 1-(di-p-anisylmethyl)-3-acetyl-4-acetoxy-2-azetidinone (397 mg) in isopropanol (6 ml) was stirred for 0.5 hour at room temperature. The reaction mixture was diluted with water and extracted with ethyl acetate. The extract was washed with water, dried over anhydrous sodium sulfate and evaporated to give 1-(di-p-anisylmethyl)-3-(1-hydroxyethyl)-4-acetoxy-2-azetidinone (the product was a mixture of two stereoisomers (about 1:1) of hydroxyethyl group). | COc1ccc(CC(Cc2ccc(OC)cc2)N2C(=O)C(C(C)O)C2OC(C)=O)cc1 | null | null | null |
1,412,790 | ord_dataset-f8e6e6a2d2bf4135b9e346456c81700f | null | 2014-01-01T00:04:00 | true | [NH2:1][C:2]1[CH:9]=[C:8]([N:10]([CH3:12])[CH3:11])[CH:7]=[CH:6][C:3]=1[CH:4]=O.[CH3:13][O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[CH2:21][CH2:22][C:23]#[N:24]>>[CH3:13][O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[CH2:21][C:22]1[C:23]([NH2:24])=[N:1][C:2]2[C:3]([CH:4]=1)=[CH:6][CH:7]=[C:8]([N:10]([CH3:12])[CH3:11])[CH:9]=2 | CN(C)c1ccc(C=O)c(N)c1 | COc1ccccc1CCC#N | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The title compound was synthesized according to EXAMPLE 11 from 2-amino-4-dimethylaminobenzaldehyde and 3-(2-methoxyphenyl)propionitrile. The reaction was performed thermally (45 min, 70-80° C.). | COc1ccccc1Cc1cc2ccc(N(C)C)cc2nc1N | null | null | null |
869,985 | ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b | null | 2009-01-01T00:03:00 | true | ClC1C=[CH:6][CH:5]=[C:4]([C:8]([O:10]O)=[O:9])[CH:3]=1>ClCCl>[CH2:5]([C:4]1([CH3:3])[C:8](=[O:9])[O:10][CH2:4][C:8](=[O:9])[O:10]1)[CH3:6] | O=C(OO)c1cccc(Cl)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | null | null | A solution of 0.5 g of cyclic keto-ester (3.5 mmol) and 1.21 g of metachloroperbenzoic acid (2 eq.) in 10 ml of dichloromethane is heated under reflux for 48 hours. After returning to ambient temperature, the solvent is eliminated under vacuum. NMR 1H analysis reveals the complete conversion of the ring with 5 members and the formation of mostly 3-ethyl-3-methyl-2,5-dioxane-1,4-dione (spectroscopic yield: 75%). NMR 1H characteristics [4.97 (s, 2H), 1.95 (q, 2H, 3JHH=7.5 Hz), 1.67 (s, 3H), 1.03 (t, 3H, 3JHH=7.5 Hz)]. | CCC1(C)OC(=O)COC1=O | null | 75 | null |
162,136 | ord_dataset-c34472859da14a81bfe0f74e60f15c43 | null | 1987-01-01T00:08:00 | true | [CH3:1][C:2]1[C:7]([CH3:8])=[C:6]([O:9][CH2:10][C:11]([F:16])([F:15])[CH:12]([F:14])[F:13])[CH:5]=[CH:4][N+:3]=1[O-].CC(OCC1C2C(=CC=CC=2)C(COC(C)=O)=C2C=1C=CC=C2)=[O:20]>S(=O)(=O)(O)O>[OH:20][CH2:1][C:2]1[C:7]([CH3:8])=[C:6]([O:9][CH2:10][C:11]([F:16])([F:15])[CH:12]([F:14])[F:13])[CH:5]=[CH:4][N:3]=1 | CC(=O)OCc1c2ccccc2c(COC(C)=O)c2ccccc12 | Cc1c(OCC(F)(F)C(F)F)cc[n+]([O-])c1C | null | O=S(=O)(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 | 110 | 4 | Concentrated sulfuric acid (two drops) was added to a solution of 2,3-dimethyl-4-(2,2,3,3-tetrafluoropropoxy)pyridine-1-oxide (2.6 g) in acetic anydride (8 ml). The mixture was stirred at 110° C. for 4 hours, which was then concentrated. The residue was dissolved in methanol (20 ml), to which was added sodium hydroxide (1.2 g) dissolved in water (5 ml). The mixture was stirred at room temperature for 30 minutes, which was concentrated. To the residue was added water, and the mixture was subjected to extraction with ethyl acetate. The extract was dried on magnesium sulfate, followed by removal of the solvent by evaporation. The residue was chromatographed on a column of silica gel (50 g), eluted with chloroform-methanol (10:1), and recrystallized from isopropyl ether to yield 1.6 g of 2-hydroxymethyl-3-methyl-4-(2,2,3,3-tetrafluoropropoxy)pyridine as yellow crystals, m.p. 67°-68° C. | Cc1c(OCC(F)(F)C(F)F)ccnc1CO | null | null | null |
1,098,234 | ord_dataset-af85e6f81c2d49f08086afd6d9e6959c | null | 2011-01-01T00:10:00 | true | [Cl:1][CH2:2][CH2:3][O:4][CH2:5][C:6]1([C:12](=[NH:15])[NH:13][OH:14])[CH2:11][CH2:10][O:9][CH2:8][CH2:7]1.[C:16]([C:23]([O:25][CH2:26][CH3:27])=[O:24])#[C:17][C:18]([O:20][CH2:21][CH3:22])=[O:19]>>[Cl:1][CH2:2][CH2:3][O:4][CH2:5][C:6]1([C:12](=[NH:15])[NH:13][O:14][C:16](=[CH:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])[C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:7][CH2:8][O:9][CH2:10][CH2:11]1 | N=C(NO)C1(COCCCl)CCOCC1 | CCOC(=O)C#CC(=O)OCC | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Reaction of 4-((2-chloroethoxy)methyl)-N-hydroxytetrahydro-2H-pyran-4-carboximidamide (10.50 g, 44.36 mmol) with diethyl acetylenedicarboxylate gave 15.25 g (84% yield) of title material as light yellow oil after chromatography. 1HNMR 400 MHz (CDCl3) δ (ppm): (mixture of E/Z isomers ratio˜3:2) 1.25-1.4 (6H, quartet of triplets), 1.6 (2H, m), 2.05 (2H, m), 3.52 (1H, s), 3.54 (1H, s), 3.65-3.85 (8H, m), 4.16-4.23 (2H, m), 4.28-4.41 (2H, m), 5.33 (1H, broad s), 5.59 (1H, broad s), 5.64 (1H, s), 5.78 (1H, s). MS (ESI+) m/e 407 [M+H+]. | CCOC(=O)C=C(ONC(=N)C1(COCCCl)CCOCC1)C(=O)OCC | null | 84 | null |
1,612,470 | ord_dataset-9cecb3a8d3b9494191b28dcefea66af2 | null | 2015-01-01T00:07:00 | true | Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][N:11]=[C:10]([CH3:13])[C:9]=2[N:14]([CH3:25])[CH:15]([CH3:24])[CH2:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:4][CH:3]=1.[CH2:26]([O:28][C:29]([C:31]1([C:34]2[CH:39]=[CH:38][C:37](B3OC(C)(C)C(C)(C)O3)=[CH:36][CH:35]=2)[CH2:33][CH2:32]1)=[O:30])[CH3:27]>>[CH2:26]([O:28][C:29]([C:31]1([C:34]2[CH:39]=[CH:38][C:37]([C:2]3[CH:7]=[CH:6][C:5]([C:8]4[O:12][N:11]=[C:10]([CH3:13])[C:9]=4[N:14]([CH3:25])[CH:15]([CH3:24])[CH2:16][CH2:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:4][CH:3]=3)=[CH:36][CH:35]=2)[CH2:32][CH2:33]1)=[O:30])[CH3:27] | Cc1noc(-c2ccc(Br)cc2)c1N(C)C(C)CCc1ccccc1 | CCOC(=O)C1(c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)CC1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Prepared according to the procedure described in Example 3, Step 5, using [5-(4-bromo-phenyl)-3-methyl-isoxazol-4-yl]-methyl-(1-methyl-3-phenyl-propyl)-amine and 1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclopropanecarboxylic acid ethyl ester. | CCOC(=O)C1(c2ccc(-c3ccc(-c4onc(C)c4N(C)C(C)CCc4ccccc4)cc3)cc2)CC1 | null | null | null |
1,261,200 | ord_dataset-266f60b4555945d6afb2d2bdf5fa04e0 | null | 2013-01-01T00:02:00 | true | [OH:1][C:2]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[C:7]2[C:3]=1[CH2:4][CH2:5][CH2:6]2.C(=O)([O-])[O-].[K+].[K+].Br[CH2:20][C:21]([C:23]1[S:24][CH:25]=[CH:26][CH:27]=1)=[O:22].O>CC(C)=O>[CH3:12][O:11][C:8]1[CH:9]=[CH:10][C:2]([O:1][CH2:20][C:21]([C:23]2[S:24][CH:25]=[CH:26][CH:27]=2)=[O:22])=[C:3]2[C:7]=1[CH2:6][CH2:5][CH2:4]2 | O=C(CBr)c1cccs1 | COc1ccc(O)c2c1CCC2 | null | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(C)=O | O | null | null | null | null | null | null | null | null | null | null | 1.5 | To the clear solution of 4-Hydroxy-7-methoxy indane (2.0 gm, 0.0121 mole) in Acetone (20 ml), Potassium carbonate (2.52 gm, 0.0182 mole) was added at room temperature and stirred for 1.5 hours. A solution of 2-Bromo-1-thiophene-2-yl-ethanone (3.75 gm, 0.0181 mole) in Acetone (10 ml) was added at 0° C. and stirred for 8 hours at room temperature. The reaction mixture was poured into the water (50 ml) and extracted with Ethyl acetate (2×100 ml). The Ethyl acetate layer was dried over Sodium sulphate and evaporated to give a crude product which was purified by column chromatography using 2% Ethyl acetate in hexane as a mobile phase The collected eluent was evaporated to yield desire product (2.1 gm) as an viscous oil. | COc1ccc(OCC(=O)c2cccs2)c2c1CCC2 | null | 60.2 | null |
1,259,146 | ord_dataset-266f60b4555945d6afb2d2bdf5fa04e0 | null | 2013-01-01T00:02:00 | true | [Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:11]([O:13][CH3:14])=[O:12])[CH:10]=1)[N:7](C(OC(C)(C)C)=O)[CH2:6][CH2:5]2.ClCCl.[OH-].[Na+]>FC(F)(F)C(O)=O>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:11]([O:13][CH3:14])=[O:12])[CH:10]=1)[NH:7][CH2:6][CH2:5]2 | COC(=O)c1cc(Br)cc2c1N(C(=O)OC(C)(C)C)CC2 | null | null | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O=C(O)C(F)(F)F | ClCCl | null | null | null | null | null | null | null | null | null | 25 | 16 | 1-(1,1-dimethylethyl) 7-methyl 5-bromo-2,3-dihydro-1H-indole-1,7-dicarboxylate (9 g, 25 mmol) was dissolved in trifluoroacetic acid (6 mL) and stirred at room temperature for 16 hours. Dichloromethane and sodium hydroxide solution (2 M) were added and the organic layer washed twice with sodium hydroxide solution until the aqueous layer pH>7. The organic layer was then concentrated in vacuo to give 6.5 g (100%) of the title compound as a brown solid. | COC(=O)c1cc(Br)cc2c1NCC2 | null | 101.5 | null |
1,285,112 | ord_dataset-d5c54236ecd94d61aaa071461bcfc426 | null | 2013-01-01T00:04:00 | true | [CH3:1][N:2]1[C:6]([CH:7]2[C:16](=O)[C:15]3[C:14]([C:18]([O:20]CC)=O)=[CH:13][CH:12]=[CH:11][C:10]=3[NH:9][CH:8]2[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[N:5][CH:4]=[N:3]1.O.[NH2:30][NH2:31]>CO>[CH3:1][N:2]1[C:6]([CH:7]2[C:16]3=[N:30][NH:31][C:18](=[O:20])[C:14]4[CH:13]=[CH:12][CH:11]=[C:10]([C:15]=43)[NH:9][CH:8]2[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[N:5][CH:4]=[N:3]1 | NN | CCOC(=O)c1cccc2c1C(=O)C(c1ncnn1C)C(c1ccccc1)N2 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CO | null | null | null | null | null | null | null | null | null | 25 | 10 | To a solution of ethyl 3-(1-methyl-1H-1,2,4-triazol-5-yl)-4-oxo-2-phenyl-1,2,3,4-tetrahydroquinoline-5-carboxylate (400 mg, 1.06 mmol) in methanol (8 mL) was added hydrazine monohydrate (0.5 mL), and the mixture was then stirred at 25° C. for 10 hr. The mixture was filtered to obtain a white solid (110 mg, yield 30%). LC-MS (ESI) m/z: 345 (M+1)+. 1H-NMR (400 MHz, DMSO-d6) δ (ppm): 3.77 (s, 3H), 4.48-4.49 (d, J=6.4 Hz, 1H), 5.16-5.19 (d, J=6.4 Hz, 1H), 7.40-7.42 (m, 2H), 7.54-7.58 (t, 1H), 7.74 (s, 1H), 12.23 (s, 1H). | Cn1ncnc1C1c2n[nH]c(=O)c3cccc(c23)NC1c1ccccc1 | null | 30 | null |
906,180 | ord_dataset-46d216f2c4374ef5b9df90427e2a4cd4 | null | 2009-01-01T00:09:00 | true | [C:1]([O:7][CH3:8])(=[O:6])[CH2:2][C:3]([CH3:5])=[O:4].[Cl:9][C:10]1[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:11]=1[CH:12]=O.CC(O)=O.CNC>CC(O)C>[Cl:9][C:10]1[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:11]=1[CH:12]=[C:2]([C:3](=[O:4])[CH3:5])[C:1]([O:7][CH3:8])=[O:6] | COC(=O)CC(C)=O | O=Cc1ccc(Cl)cc1Cl | null | CNC | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(=O)O | CC(C)O | null | null | null | null | null | null | null | null | null | 40 | null | To a stirred solution of methyl acetoacetate (345 mg, 2.97 mmol) and 2,4-dichlorobenzaldehyde (500 mg, 2.86 mmol) in 2-propanol (5 mL) was added AcOH (7 mg, 0.11 mmol) and dimethylamine (0.06 mL, 2M in THF, 0.11 mmol). The reaction was heated to 40° C. for 4 hrs followed by cooling to ambient temperature for 15 hrs. The reaction was concentrated and purified by flash chromatography (silica gel, 30% EtOAc/hexane) to give methyl 2-(2,4-dichlorobenzylidene)-3-oxobutanoate as a mixture of two isomers (colorless oil, 610 mg, 78%). | COC(=O)C(=Cc1ccc(Cl)cc1Cl)C(C)=O | null | null | null |
1,375,784 | ord_dataset-d23f2f15886d4c22b7d7ba5f0e203e81 | null | 2013-01-01T00:12:00 | true | [N+:1]([O-:31])([O:3][C@@H:4]1[CH:21]2[C@:16]([CH3:22])([CH2:17][CH2:18][CH2:19][CH2:20]2)[C@@H:15]2[C@H:6]([C@H:7]3[C@@:11]([CH2:13][CH2:14]2)([CH3:12])[C:10]24OCCO[C:9]2(OCC[O:23]4)[CH2:8]3)[CH2:5]1)=[O:2].CC1C=CC(S(O)(=O)=[O:40])=CC=1.O.C([O-])(O)=O.[Na+]>CC(C)=O>[N+:1]([O-:31])([O:3][C@@H:4]1[CH:21]2[C@:16]([CH3:22])([CH2:17][CH2:18][C:19](=[O:40])[CH2:20]2)[C@@H:15]2[C@H:6]([C@H:7]3[C@@:11]([CH2:13][CH2:14]2)([CH3:12])[C:10](=[O:23])[CH2:9][CH2:8]3)[CH2:5]1)=[O:2] | Cc1ccc(S(=O)(=O)O)cc1 | C[C@]12CCCCC1[C@@H](O[N+](=O)[O-])C[C@@H]1[C@@H]2CC[C@@]2(C)[C@H]1CC13OCCOC12OCCO3 | null | O=C([O-])O | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CC(C)=O | null | null | null | null | null | null | null | null | null | null | null | A solution of 3,3:17,17-bis(ethylendioxy)androstane-6α-yl nitrate (2.50 g) and pTSA.H2O (6.05 g) in acetone (150 mL) was stirred at room temperature for 1.5 h. The solution was neutralized by addition of 5% aqueous NaHCO3, and acetone was evaporated. The aqueous phase was extracted with CH2Cl2 (3×50 mL). The combined organic extracts were washed with H2O, dried over Na2SO4 and evaporated to dryness. The residue was purified by flash chromatography (SiO2, cyclohexane/acetone/CH2Cl2 70/15/15) to give the title compound II-aa as a white solid (1.66 g, 75%). 1H-NMR (300 MHz, acetone-d6, ppm from TMS): δ 5.09 (ddd, 1H), 2.60-0.95 (m, 17H), 1.25 (s, 3H), 0.90 (s, 3H). | C[C@]12CCC(=O)CC1[C@@H](O[N+](=O)[O-])C[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12 | null | null | null |
1,167,024 | ord_dataset-d24cc23b3db94284bb83a2ccdd9eb880 | null | 2012-01-01T00:05:00 | true | [H-].[Na+].[CH3:3][O:4][C:5]([C:7]1[CH:16]=[CH:15][C:14]2[C:9](=[CH:10][CH:11]=[C:12]([OH:17])[CH:13]=2)[CH:8]=1)=[O:6].Cl[C:19]1[C:28]2[C:23](=[CH:24][C:25]([O:31][CH3:32])=[C:26]([O:29][CH3:30])[CH:27]=2)[N:22]=[CH:21][N:20]=1>CN(C=O)C>[CH3:30][O:29][C:26]1[CH:27]=[C:28]2[C:23](=[CH:24][C:25]=1[O:31][CH3:32])[N:22]=[CH:21][N:20]=[C:19]2[O:17][C:12]1[CH:13]=[C:14]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([C:5]([O:4][CH3:3])=[O:6])[CH:16]=[CH:15]2 | COc1cc2ncnc(Cl)c2cc1OC | COC(=O)c1ccc2cc(O)ccc2c1 | null | [H-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | 60 | 0.33 | To a stirred mixture of NaH (200 mg, 60% in mineral oil, 5.0 mmol, Aldrich) in 10 mL of DMF at RT was added 6-hydroxy-naphthalene-2-carboxylic acid methyl ester (Step a, 675 mg, 3.34 mmol). After 20 min, 4-chloro-6,7-dimethoxy-quinazoline (750 mg, 3.34 mmol, Oakwood) was added and the reaction was heated to 60° C. for 20 min. The reaction was cooled to RT, quenched with saturated aqueous NH4Cl solution (30 mL) and extracted with CHCl3 (30 mL). The organic solution was washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography (30% EtOAc/hexane) to give the title compound as a white solid. MS (ESI, pos. ion) m/z: 390.9 (M+1). Mass Calc'd for C22H18N2O5: 390.12. | COC(=O)c1ccc2cc(Oc3ncnc4cc(OC)c(OC)cc34)ccc2c1 | null | null | null |
1,334,801 | ord_dataset-08852243bba44cb28769a5833f1515fe | null | 2013-01-01T00:09:00 | true | [Cl:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[C:12]([NH2:19])=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1.N1C=CC=CC=1.[C:26](Cl)(=[O:33])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C(=O)([O-])O.[Na+]>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[C:13]([C:15]([F:17])([F:18])[F:16])[C:12]([NH:19][C:26](=[O:33])[C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1 | O=C(Cl)c1ccccc1 | Nc1cnc(Nc2cccc(Cl)c2)nc1C(F)(F)F | null | O=C([O-])O | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | c1ccncc1 | null | null | null | null | null | null | null | null | null | 25 | 3 | To a mixture of N2-(3-chlorophenyl)-4-(trifluoromethyl)pyrimidine-2,5-diamine (150 mg), pyridine (84 μL) and dichloromethane (3 mL) was added benzoyl chloride (72 μL) under ice-cooling, followed by stirring at room temperature for 3 hours. To the reaction mixture was added a saturated aqueous sodium hydrogen carbonate solution and the aqueous layer was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate, and then the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate), and the obtained residue was solidified from a mixed solvent of hexane and ethyl acetate to obtain N-{2-[(3-chlorophenyl)amino]-4-(trifluoromethyl)pyrimidin-5-yl}benzamide (166 mg) as a white powder. | O=C(Nc1cnc(Nc2cccc(Cl)c2)nc1C(F)(F)F)c1ccccc1 | null | null | null |
1,093,382 | ord_dataset-52a37d876ddb453e86de0c15fa233d29 | null | 2011-01-01T00:09:00 | true | [O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH:10]([C:15]1[CH:27]=[CH:26][C:18]([C:19]([O:21]C(C)(C)C)=[O:20])=[CH:17][CH:16]=1)[C:11]([O:13][CH3:14])=[O:12].FC(F)(F)C(O)=O>C(Cl)Cl>[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH:10]([C:15]1[CH:16]=[CH:17][C:18]([C:19]([OH:21])=[O:20])=[CH:26][CH:27]=1)[C:11]([O:13][CH3:14])=[O:12] | COC(=O)C(c1ccc(C(=O)OC(C)(C)C)cc1)c1nc2ccccc2o1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O=C(O)C(F)(F)F | ClCCl | null | null | null | null | null | null | null | null | null | 25 | 1 | To a solution of tert-butyl 4-[1-(1,3-benzoxazol-2-yl)-2-methoxy-2-oxoethyl]benzoate (90 mg, 0.25 mmol) in methylene chloride (2 mL) was added trifluoroacetic acid (0.5 mL) and the solution was stirred at ambient temperature for 1 hour. The reaction was evaporated to dryness to give the title compound as a clear oil. ESIMS calcd 312.1 (M++H), found 312.0 (M++M). | COC(=O)C(c1ccc(C(=O)O)cc1)c1nc2ccccc2o1 | null | null | null |
150,423 | ord_dataset-b9a9e369e9da4413999591aa08f4c3e3 | null | 1986-01-01T00:11:00 | true | [O:1]=[C:2]1[CH2:7][CH2:6][CH2:5][CH2:4][CH:3]1[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]([CH3:19])[C:16]([OH:18])=[O:17])=[CH:11][CH:10]=1.CCC(C)[BH-](C(C)CC)C(C)CC.[K+].Cl>O1CCCC1>[OH:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[CH2:8][C:9]1[CH:10]=[CH:11][C:12]([CH:15]([CH3:19])[C:16]([OH:18])=[O:17])=[CH:13][CH:14]=1 | CC(C(=O)O)c1ccc(CC2CCCCC2=O)cc1 | null | null | CCC(C)[BH-](C(C)CC)C(C)CC | Cl | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | -78 | 1 | 10.0 g of (±)-2-[4-(2-oxocyclohexylmethyl)phenyl]propionic acid were dissolved in 150 ml of tetrahydrofuran. The solution was cooled to -78° C. and, whilst maintaining the solution at this temperature and under a stream of nitrogen, 200 ml of K-Selectride (as a 0.5 molar tetrahydrofuran solution) were added dropwise. When the whole of the K-Selectride had been added, the reaction mixture was stirred for 1 hour at 0° C., after which it was cooled to -10° C. and 400 ml of a 0.5N solution of hydrochloric acid was added through a dropping funnel. The reaction mixture was stirred for 1 hour, after which it was extracted with diethyl ether. The extract was washed with water and dried over anhydrous sodium sulphate. The solvent was distilled off, giving 10.5 g of the title compound in the form of crystals. These were recrystallised from a mixture of diethyl ether and hexane, giving the title compound as pure crystals melting at 130°-133° C. | CC(C(=O)O)c1ccc(C[C@@H]2CCCC[C@@H]2O)cc1 | null | 104.2 | null |
566,791 | ord_dataset-5c8a417a8ba04cf0b7f78b9db9af1d01 | null | 2002-01-01T00:10:00 | true | [CH3:1][O:2][C:3]([C:5]12[CH2:14][CH:9]3[CH2:10][CH:11]([CH2:13][C:7]([C:15]([NH:17][CH:18]([CH2:26][C:27]#[CH:28])[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[O:16])([CH2:8]3)[CH2:6]1)[CH2:12]2)=[O:4].CCN(CC)CC.[CH3:36][N:37]([CH3:41])[C:38](Cl)=[O:39]>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]12[CH2:14][CH:9]3[CH2:10][CH:11]([CH2:13][C:7]([C:15]([NH:17][CH:18]([CH2:26][C:27]#[C:28][C:38]([N:37]([CH3:41])[CH3:36])=[O:39])[C:19]([O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:20])=[O:16])([CH2:8]3)[CH2:6]1)[CH2:12]2)=[O:4] | CN(C)C(=O)Cl | C#CCC(NC(=O)C12CC3CC(C1)CC(C(=O)OC)(C3)C2)C(=O)OC(C)(C)C | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(CC)CC | CN(C)C=O | null | null | null | null | null | null | null | null | null | 25 | 8 | The compound from Step A of Example 49 (0.389 g, 1 mmol) was dissolved in dry DMF (5 mL) with dichlorobis(diphenylphosphine)palladium (II) (0.02 eq), Cul (0.02eq), Et3N (0.4 eq, 3 mL), and N,N-dimethylcarbamyl chloride (1.0 eq, 92 μL). The reaction mixture was stirred overnight at room temperature and then at 70° C. for 1 hour. The mixture was filtered through a pad of Celite and the solvent removed under reduced pressure. The crude product was purified by column chromatography (silica gel; EtOAc/hexanes, 2:3) to afford the title compound. | COC(=O)C12CC3CC(CC(C(=O)NC(CC#CC(=O)N(C)C)C(=O)OC(C)(C)C)(C3)C1)C2 | null | null | null |
1,414,231 | ord_dataset-f8e6e6a2d2bf4135b9e346456c81700f | null | 2014-01-01T00:04:00 | true | [O:1]1[CH2:5][CH2:4][CH:3]([O:6][C:7]2[CH:15]=[C:14]3[C:10]([CH:11]=[CH:12][NH:13]3)=[CH:9][CH:8]=2)[CH2:2]1.[CH3:16][C:17]1[C:22](/[CH:23]=[CH:24]/[N+:25]([O-:27])=[O:26])=[CH:21][CH:20]=[CH:19][C:18]=1[NH:28][C:29](=[O:38])[O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>C1COCC1>[CH3:16][C:17]1[C:22]([CH:23]([C:11]2[C:10]3[C:14](=[CH:15][C:7]([O:6][CH:3]4[CH2:4][CH2:5][O:1][CH2:2]4)=[CH:8][CH:9]=3)[NH:13][CH:12]=2)[CH2:24][N+:25]([O-:27])=[O:26])=[CH:21][CH:20]=[CH:19][C:18]=1[NH:28][C:29](=[O:38])[O:30][CH2:31][C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1 | c1cc2ccc(OC3CCOC3)cc2[nH]1 | Cc1c(/C=C/[N+](=O)[O-])cccc1NC(=O)OCc1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | null | null | 6-(Tetrahydrofuran-3-yloxy)-1H-indole (0.632 g, 3.11 mmol) and (E)-benzyl 2-methyl-3-(2-nitrovinyl)phenylcarbamate (0.800 g, 2.56 mmol) were dissolved in THF (50 mL). The solution was then concentrated under vacuum to dryness. The solid mixture was melted at 130° C. and heated at this temperature for 6 hr. The mixture was subjected to ISCO (120 g silica gel, solid loading, 25-65% ethyl acetate/hexane) to afford the desired product (0.612 g, 1.187 mmol, 46.3% yield) as a beige solid. | Cc1c(NC(=O)OCc2ccccc2)cccc1C(C[N+](=O)[O-])c1c[nH]c2cc(OC3CCOC3)ccc12 | null | 46.4 | null |
1,570,078 | ord_dataset-9741bb5fd93044078df2a45f45733054 | null | 2015-01-01T00:04:00 | true | [NH:1]1[CH2:6][CH2:5][CH2:4][C@@H:3]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH2:2]1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:22][C:23]1[CH:30]=[CH:29][CH:28]=[CH:27][C:24]=1[C:25]#[N:26]>>[C:25]([C:24]1[CH:27]=[CH:28][CH:29]=[CH:30][C:23]=1[CH2:22][N:1]1[CH2:6][CH2:5][CH2:4][C@@H:3]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:11])([CH3:13])[CH3:12])[CH2:2]1)#[N:26] | N#Cc1ccccc1CBr | CC(C)(C)OC(=O)N[C@@H]1CCCNC1 | null | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | 25 | 2.5 | To a microwave vial equipped with a stir bar was added tert-butyl (3R)-piperidin-3-ylcarbamate (3000 mg, 14.98 mmol), Potassium Carbonate (6211 mg, 44.9 mmol), and 2-(bromomethyl)benzonitrile (3230 mg, 16.48 mmol). The vial was sealed and stirred at room temperature. The LCMS taken after 2.5 hours indicates the formation of the desired product. The crude reaction mixture was filtered and concentrated in vacuo. The material was dry loaded onto a 50 g column. The column was run from 100% dichloromethane to 15% methanol. The desired product eluted and the fractions were collected and concentrated in vacuo. | CC(C)(C)OC(=O)N[C@@H]1CCCN(Cc2ccccc2C#N)C1 | null | null | null |
288,508 | ord_dataset-96711be098434bc9ab567cb77fa3362b | null | 1994-01-01T00:04:00 | true | [NH2:1]N.[CH3:3][N:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH:5]1[CH2:10][CH2:11]C1C=CC=C2C(NC(=O)C=12)=O>CO>[CH3:3][N:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH:5]1[CH2:10][CH2:11][NH2:1] | NN | CN1CCNCC1CCc1cccc2c1C(=O)NC2=O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | null | null | Hydrazine (aqueous solution at 35% by wt.) (0.15 ml; 1.6 mmoles) was added to 2-(N-methylpiperazinyl)ethylphthalimide (218 mg; 0.8 mmoles) in methanol (5 ml) and the resulting solution was refluxed. Reaction times and process as per Example 1. | CN1CCNCC1CCN | null | null | null |
828,604 | ord_dataset-47bd90bf5ec74fcd99ce250a56e18c8f | null | 2008-01-01T00:07:00 | true | [CH2:1]([OH:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].[C:18]1([CH3:27])[CH:23]=[CH:22][C:21]([N:24]=[C:25]=[O:26])=[CH:20][CH:19]=1>C1(C)C=CC=CC=1>[CH3:27][C:18]1[CH:23]=[CH:22][C:21]([NH:24][C:25](=[O:26])[O:17][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])=[CH:20][CH:19]=1 | Cc1ccc(N=C=O)cc1 | CCCCCCCCCCCCCCCCO | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Cc1ccccc1 | null | null | null | null | null | null | null | null | null | null | 25 | 12 | 91 g (375 mmol) of 1-hexadecanol were added to a solution of 50 g (375 mmol) of p-tolyl isocyanate in 50 ml of toluene, and the resulting solution was heated under reflux for 8 h. After cooling to room temperature and stirring at this temperature for 12 h, the precipitated solid was filtered off. The colourless solid was washed twice with 10 ml of toluene each time and then dried in vacuo. 80 g (213 mmol, 57%) of the desired carbamate were obtained in the form of a colourless solid with a melting point of 75° C. The melting point agreed with literature data (75-76° C., Microchem J. 1962, 6, 179). | CCCCCCCCCCCCCCCCOC(=O)Nc1ccc(C)cc1 | null | 56.8 | null |
1,162,496 | ord_dataset-d24cc23b3db94284bb83a2ccdd9eb880 | null | 2012-01-01T00:05:00 | true | C(OC([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]([CH:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)=[O:16])[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[N:11]1([C:15]([CH:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)=[O:16])[CH2:12][CH2:13][CH2:14][NH:8][CH2:9][CH2:10]1 | CC(C)(C)OC(=O)N1CCCN(C(=O)C2CCOCC2)CC1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O=C(O)C(F)(F)F | ClCCl | null | null | null | null | null | null | null | null | null | 25 | 6 | To a solution of 13 g (41.7 mmol) of 4-(tetrahydro-pyran-4-carbonyl)-[1,4]diazepane-1-carboxylic acid tert-butyl ester in DCM (260 mL) were added 32.5 mL of trifluoroacetic acid. The reaction was stirred for 6 h at room temperature. The solvent was removed under reduced pressure. The residual oil was azeotroped with DCM (3×20 mL), chloroform (2×20 mL) and toluene (3×20 mL) to afford 22.9 g of [1,4]diazepan-1-yl-(tetrahydro-pyran-4-yl)-methanone as triple trifluoroacetic acid salt; ES−MS: m/z 213 [M+H+] | O=C(C1CCOCC1)N1CCCNCC1 | null | 258.7 | null |
913,454 | ord_dataset-c663259b80f947e2a8923796fb0e9a6b | null | 2009-01-01T00:10:00 | true | [CH2:1]1[C:9]2[C:8]3[CH:10]=[CH:11][CH:12]=[CH:13][C:7]=3[O:6][C:5]=2[CH2:4][CH2:3][CH:2]1[NH2:14].[C:15]([C:19]1[CH:27]=[CH:26][C:22]([C:23](Cl)=[O:24])=[CH:21][CH:20]=1)([CH3:18])([CH3:17])[CH3:16].C(N(CC)CC)C>O1CCCC1>[C:15]([C:19]1[CH:20]=[CH:21][C:22]([C:23]([NH:14][C:2]2[CH:3]=[CH:4][C:5]3[O:6][C:7]4[CH2:13][CH2:12][CH2:11][CH2:10][C:8]=4[C:9]=3[CH:1]=2)=[O:24])=[CH:26][CH:27]=1)([CH3:18])([CH3:16])[CH3:17] | CC(C)(C)c1ccc(C(=O)Cl)cc1 | NC1CCc2oc3ccccc3c2C1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(CC)CC | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | null | Following the procedure of Example 1, tetrahydro-dibenzofuran-2-ylamine (0.94 g, 5.0 mmol), 4-t-butylbenzoyl chloride (1.1 mL, 5.3 mmol), and triethylamine (2.1 mL, 15 mmol) in tetrahydrofuran (20 mL) provided 4-tert-butyl-N-(6,7,8,9-tetrahydro-dibenzofuran-2-yl)-benzamide (1.2 g). Mp 185-186° C.; Anal. Calcd. for C23H25NO2: C, 79.51; H, 7.25; N, 4.03; Found: C, 79.33; H, 7.27; N, 3.94. | CC(C)(C)c1ccc(C(=O)Nc2ccc3oc4c(c3c2)CCCC4)cc1 | null | 69.1 | null |
1,132,829 | ord_dataset-aaeaab5f3720492494c1cbbdd0ed2820 | null | 2012-01-01T00:02:00 | true | [CH3:1][CH:2]([CH3:15])[CH2:3][NH:4][C:5]1[CH:14]=[CH:13][C:8]2[N:9]=[C:10]([SH:12])[S:11][C:7]=2[CH:6]=1.[F:16][C:17]([F:28])([F:27])[C:18]1[CH:23]=[CH:22][C:21]([N:24]=[C:25]=[O:26])=[CH:20][CH:19]=1>ClCCl>[SH:12][C:10]1[S:11][C:7]2[CH:6]=[C:5]([N:4]([CH2:3][CH:2]([CH3:15])[CH3:1])[C:25]([NH:24][C:21]3[CH:20]=[CH:19][C:18]([C:17]([F:16])([F:27])[F:28])=[CH:23][CH:22]=3)=[O:26])[CH:14]=[CH:13][C:8]=2[N:9]=1 | O=C=Nc1ccc(C(F)(F)F)cc1 | CC(C)CNc1ccc2nc(S)sc2c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | null | 8 | Into 50 ml round bottomed flask were added 6-[(2-methylpropyl)amino]-1,3-benzothiazole-2-thiol (52.36 mg, 0.22 mmol), dichloromethane (10 ml), and α,α,α-trifluoro-p-tolyl isocyanate (41.1 mg, 0.22 mmol). The reaction mixture was stirred 8 h, filtered, and the solid that was obtained was triturated with chloroform, followed with chloroform/methanol (9:1 mixture) to give 60 mg (64%) of the title compound. 1H NMR (DMSO-d6) δ=0.84 (d, 6H), 1.66 (m, 1H), 3.49 (d, 2H), 7.30 (s, 2H), 7.50 (d, 2H), 7.60 (d, 2H), 7.71 (s, 1H); ESIMS: m/z 424 (M−H). | CC(C)CN(C(=O)Nc1ccc(C(F)(F)F)cc1)c1ccc2nc(S)sc2c1 | null | 64.1 | null |
642,408 | ord_dataset-ce71a906ea9c4399a2014cbaaff88c8f | null | 2004-01-01T00:07:00 | true | C([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([C:13]([O:15][CH3:16])=[O:14])[CH:11]=2)[C:6](=[C:17](OCC)[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:5]1=[O:27])(=O)C.[N:28]1([CH2:34][C:35]2[CH:41]=[CH:40][C:38]([NH2:39])=[CH:37][CH:36]=2)[CH2:33][CH2:32][S:31][CH2:30][CH2:29]1>>[N:28]1([CH2:34][C:35]2[CH:41]=[CH:40][C:38]([NH:39]/[C:17](=[C:6]3\[C:5](=[O:27])[NH:4][C:12]4[C:7]\3=[CH:8][CH:9]=[C:10]([C:13]([O:15][CH3:16])=[O:14])[CH:11]=4)/[C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:37][CH:36]=2)[CH2:29][CH2:30][S:31][CH2:32][CH2:33]1 | Nc1ccc(CN2CCSCC2)cc1 | CCOC(=C1C(=O)N(C(C)=O)c2cc(C(=O)OC)ccc21)c1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Prepared from 1-acetyl-3-(1-ethoxy-1-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(thiomorpholin-4-yl-methyl)-aniline Rf value: 0.4 (silica gel, methylene chloride/methanol=15:1) C28H27N3O3S | COC(=O)c1ccc2c(c1)NC(=O)/C2=C(\Nc1ccc(CN2CCSCC2)cc1)c1ccccc1 | null | null | null |
990,982 | ord_dataset-b6d8835b0c934476a36e6149e7597487 | null | 2010-01-01T00:09:00 | true | [Cl:1][C:2]1[CH:9]=[C:8]([F:10])[C:5]([CH:6]=[O:7])=[C:4]([F:11])[CH:3]=1.O1CCCC1.[BH4-].[Na+]>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([F:11])[C:5]([CH2:6][OH:7])=[C:8]([F:10])[CH:9]=1 | O=Cc1c(F)cc(Cl)cc1F | null | null | [BH4-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | CCO | null | null | null | null | null | null | null | null | null | 25 | 0.5 | To a mixture of 4-chloro-2,6-difluoro-benzaldehyde (5.7 g, 32 mmol), tetrahydrofuran (150 mL) and ethanol (20 mL) was added sodium borohydride (1.2 g, 32 mmol) at 0° C. The mixture was stirred for 30 minutes, warmed to ambient temperature, and additional sodium borohydride (0.40 g, 11 mmol) was added to drive the reaction to completion (TLC). The mixture was concentrated in vacuo, diluted with ether and treated cautiously with 1M aqueous HCl. The aqueous phase was extracted 3× with ether, and the combined organic layers were dried over MgSO4, filtered and concentrated. Trituration of the residue with pentane afforded 4.8 g (83%) of (4-chloro-2,6-difluoro-phenyl)-methanol as a colorless solid. 1H NMR (300 MHz, CDCl3) δ 7.04 (d, 2H, J=7.1 Hz), 4.73 (s, 2H) ppm. | OCc1c(F)cc(Cl)cc1F | null | 84 | null |
903,450 | ord_dataset-46d216f2c4374ef5b9df90427e2a4cd4 | null | 2009-01-01T00:09:00 | true | [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][S:9]([C:12]1[S:16][C:15]2[CH:17]=[CH:18][CH:19]=[CH:20][C:14]=2[CH:13]=1)(=[O:11])=[O:10].CS([C:25]1[CH:26]=[CH:27][C:28]([O:35][CH3:36])=[C:29]([S:31](Cl)(=[O:33])=[O:32])[CH:30]=1)(=O)=O>C(Cl)Cl.N1C=CC=CC=1>[CH3:12][S:9]([C:26]1[CH:25]=[CH:30][C:29]([S:31]([NH:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[NH:8][S:9]([C:12]2[S:16][C:15]3[CH:17]=[CH:18][CH:19]=[CH:20][C:14]=3[CH:13]=2)(=[O:11])=[O:10])(=[O:32])=[O:33])=[C:28]([O:35][CH3:36])[CH:27]=1)(=[O:11])=[O:10] | COc1ccc(S(C)(=O)=O)cc1S(=O)(=O)Cl | Nc1ccccc1NS(=O)(=O)c1cc2ccccc2s1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | c1ccncc1 | ClCCl | null | null | null | null | null | null | null | null | null | 25 | 8 | To a solution of benzo[b]thiophene-2-sulfonic acid (2-amino-phenyl)-amide (1 mmol, prepared as in Example 1) in DCM (2 mL) and pyridine (2 mL), 5-methanesulfonyl-2-methoxybenzenesulfonyl chloride (1.1 mmol) was added at RT and the reaction mixture was then allowed to stir at RT overnight. The reaction mixture was then diluted with DCM (10 mL). The organic phase was washed with 10% aqueous HCl (10 mL), water (10 mL) and brine (10 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue obtained was purified by flash column chromatography eluting with DCM/EtOAc to obtain 330 mg of benzo[b]thiophene-2-sulfonic acid [2-(4-methanesulfonyl-2-methoxy-benzenesulfonylamino)phenyl]-amide. LC: Tr 1.06 min; MS: 553.8 (M+1)+. | COc1cc(S(C)(=O)=O)ccc1S(=O)(=O)Nc1ccccc1NS(=O)(=O)c1cc2ccccc2s1 | null | 119.4 | null |
1,258,273 | ord_dataset-266f60b4555945d6afb2d2bdf5fa04e0 | null | 2013-01-01T00:02:00 | true | [Cl-].[CH3:2][C:3]1[CH:4]=[C:5]([NH:10][NH3+:11])[CH:6]=[CH:7][C:8]=1[CH3:9].[C:12](OCC)(=[O:17])[CH2:13][C:14]([CH3:16])=O.C([O-])(=O)C.[Na+].C(O)(=O)C>C(O)C>[CH3:2][C:3]1[CH:4]=[C:5]([N:10]2[C:12]([OH:17])=[CH:13][C:14]([CH3:16])=[N:11]2)[CH:6]=[CH:7][C:8]=1[CH3:9] | Cc1ccc(N[NH3+])cc1C | CCOC(=O)CC(C)=O | null | CC(=O)[O-] | [Cl-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | CC(=O)O | null | null | null | null | null | null | null | null | null | null | null | 2-(3,4-Dimethylphenyl)hydrazinium chloride (900 g, 5.21 mol), ethyl acetoacetate (678 g, 5.21 mol), sodium acetate (428 g, 5.21 mol) and glacial acetic acid (10 L) were stirred at 118° C. for about 24 hours. The resulting mixture was cooled and concentrated, and the residue was dissolved in dichloromethane (10 L) and carefully washed with saturated sodium bicarbonate (3×3 L). The organic layer was concentrated to afford a solid. The solid was dissolved in ethanol (450 mL) under reflux. Petroleum ether (7.2 L) was slowly added, and the resulting mixture was cooled and filtered to afford the title compound (748 g, 71%). PXRD analysis provided the diffractogram as shown in FIG. 31. | Cc1cc(O)n(-c2ccc(C)c(C)c2)n1 | null | 71 | null |
816,486 | ord_dataset-50f99930fc41474db226bc80774b38df | null | 2008-01-01T00:04:00 | true | [CH2:1]([O:3][C:4]([C:6]1[NH:7][CH:8]=[N:9][C:10]=1[CH3:11])=[O:5])[CH3:2].C1C(=O)N([I:19])C(=O)C1>C1COCC1>[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]([I:19])=[N:9][C:10]=1[CH3:11])=[O:5])[CH3:2] | O=C1CCC(=O)N1I | CCOC(=O)c1[nH]cnc1C | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | null | null | A solution of 5 g 5-Methyl-3H-imidazole-4-carboxylic acid ethyl ester and 7.2 g NIS in 50 ml THF were refluxed for 10 h. After cooling, the solvent was removed under reduced pressure and the residue taken-up in ethyl acetate, washed with sat. NaS2O3 solution and dried over MgSO4. After removal of the solvent under reduced pressure the product was purified by recrystallisation from ethyl acetate. Yield: 7 g | CCOC(=O)c1[nH]c(I)nc1C | null | null | null |
1,618,492 | ord_dataset-35c51552812941cda45194a013d34bb9 | null | 2015-01-01T00:08:00 | true | [Na].C(O[CH:7]=[CH:8][C:9](=O)[C:10]([F:16])([F:15])[C:11]([F:14])([F:13])[F:12])CCC.[C:18]([NH2:24])(=[O:23])[CH2:19][C:20]([NH2:22])=[O:21]>C(O)C>[O:21]=[C:20]1[C:19]([C:18]([NH2:24])=[O:23])=[CH:7][CH:8]=[C:9]([C:10]([F:15])([F:16])[C:11]([F:12])([F:13])[F:14])[NH:22]1 | CCCCOC=CC(=O)C(F)(F)C(F)(F)F | NC(=O)CC(N)=O | null | [Na] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | null | null | null | null | null | null | null | null | null | null | null | null | 0.22 g (9.7 mmol) of sodium was dissolved in 50 ml of ethanol, 2 g (8.1 mmol) of 1-butoxy-4,4,5,5,5-pentafluoropent-1-en-3-one and 0.86 g (8.1 mmol) malonamide were added and the mixture was heated under reflux for 7 h. The mixture was concentrated, and 1N hydrochloric acid was added. The resulting precipitate was filtered off with suction and dried. This gave 1.9 g (94% of theory) of a yellow powder. | NC(=O)c1ccc(C(F)(F)C(F)(F)F)[nH]c1=O | null | null | null |
771,642 | ord_dataset-8214eb8444a44dc2900ccb42dbeff15e | null | 2007-01-01T00:05:00 | true | [CH3:1][S:2]([C:5]1[CH:6]=[CH:7][C:8]([O:14][C@@H:15]([CH3:20])[C:16]([F:19])([F:18])[F:17])=[C:9]([CH:13]=1)[C:10]([OH:12])=O)(=[O:4])=[O:3].FC(F)(F)C(O)=O.[F:28][C:29]([F:42])([F:41])[C:30]1[S:34][C:33]([N:35]2[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]2)=[N:32][N:31]=1>>[CH3:1][S:2]([C:5]1[CH:6]=[CH:7][C:8]([O:14][C@@H:15]([CH3:20])[C:16]([F:19])([F:18])[F:17])=[C:9]([C:10]([N:38]2[CH2:37][CH2:36][N:35]([C:33]3[S:34][C:30]([C:29]([F:41])([F:28])[F:42])=[N:31][N:32]=3)[CH2:40][CH2:39]2)=[O:12])[CH:13]=1)(=[O:3])=[O:4] | FC(F)(F)c1nnc(N2CCNCC2)s1 | C[C@H](Oc1ccc(S(C)(=O)=O)cc1C(=O)O)C(F)(F)F | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O=C(O)C(F)(F)F | null | null | null | null | null | null | null | null | null | null | null | null | Prepared in analogy to example 1 (b) from 5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-benzoic acid (Example A15) and 1-(5-trifluoromethyl-[1,3,4]thiadiazol-2-yl)-piperazine trifluoroacetate (Example 62(b)). The crude material was purified by chromatography (SiO2, ethyl acetate/heptane) to yield the title compound as an off-white solid (yield 52%). MS (m/e): 533.0 (M+H+, 100%). | C[C@H](Oc1ccc(S(C)(=O)=O)cc1C(=O)N1CCN(c2nnc(C(F)(F)F)s2)CC1)C(F)(F)F | null | 52 | null |
648,540 | ord_dataset-5d77a731aa10488794c824ad12021f57 | null | 2004-01-01T00:09:00 | true | C([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH:11]=2)[C:6](=[C:19](OCC)[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:5]1=[O:29])(=O)C.[CH3:30][N:31]([CH3:46])[CH2:32][CH2:33][N:34]([S:42]([CH3:45])(=[O:44])=[O:43])[C:35]1[CH:40]=[CH:39][C:38]([NH2:41])=[CH:37][CH:36]=1>>[CH3:30][N:31]([CH3:46])[CH2:32][CH2:33][N:34]([C:35]1[CH:36]=[CH:37][C:38]([NH:41]/[C:19](=[C:6]2\[C:5](=[O:29])[NH:4][C:12]3[C:7]\2=[CH:8][CH:9]=[C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:11]=3)/[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)=[CH:39][CH:40]=1)[S:42]([CH3:45])(=[O:44])=[O:43] | CCOC(=C1C(=O)N(C(C)=O)c2cc(-c3ccccc3)ccc21)c1ccccc1 | CN(C)CCN(c1ccc(N)cc1)S(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 | null | null | null | null | null | Prepared from 1-acetyl-3-(1-ethoxy-1-phenyl-methylidene)-6-phenyl-2-indolinone and N-(2-dimethylamino-ethyl)-N-methylsulphonyl-p-phenylenediamine | CN(C)CCN(c1ccc(N/C(=C2\C(=O)Nc3cc(-c4ccccc4)ccc32)c2ccccc2)cc1)S(C)(=O)=O | null | null | null |
823,978 | ord_dataset-0ca5627a13c049a99463095023b09fe5 | null | 2008-01-01T00:06:00 | true | [CH3:1][C@H:2]1[NH:7][C@@H:6]([CH3:8])[CH2:5][N:4]([C:9]2[CH:10]=[CH:11][C:12]([O:16][CH3:17])=[C:13]([CH:15]=2)[NH2:14])[CH2:3]1.[Cl:18][C:19]1[S:23][N:22]=[C:21]([C:24]2[S:28][C:27]([S:29](Cl)(=[O:31])=[O:30])=[CH:26][CH:25]=2)[N:20]=1>ClCCl.N1C=CC=CC=1>[Cl:18][C:19]1[S:23][N:22]=[C:21]([C:24]2[S:28][C:27]([S:29]([NH:14][C:13]3[CH:15]=[C:9]([N:4]4[CH2:3][C@H:2]([CH3:1])[NH:7][C@H:6]([CH3:8])[CH2:5]4)[CH:10]=[CH:11][C:12]=3[O:16][CH3:17])(=[O:31])=[O:30])=[CH:26][CH:25]=2)[N:20]=1 | O=S(=O)(Cl)c1ccc(-c2nsc(Cl)n2)s1 | COc1ccc(N2C[C@@H](C)N[C@@H](C)C2)cc1N | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | c1ccncc1 | ClCCl | null | null | null | null | null | null | null | null | null | 25 | 8 | A solution of 5-(cis-3,5-dimethyl-1-piperazinyl)-2-(methyloxy)aniline (D4) (33 mg, 0.14 mmol) in dichloromethane (2 ml) and pyridine (0.5 ml) was treated with 5-(5-chloro-1,2,4-thiadiazol-3-yl)-2-thiophenesulfonyl chloride (50 mg, 0.17 mmol) and the resulting mixture stirred at room temperature overnight. The mixture was then concentrated in vacuo, co-evaporated with toluene and the crude product purified by mass directed autoprep HPLC to afford the desired product which was characterized as the hydrochloride salt. MS (ES+) m/e 500/502 [M+H]+. | COc1ccc(N2C[C@@H](C)N[C@@H](C)C2)cc1NS(=O)(=O)c1ccc(-c2nsc(Cl)n2)s1 | null | null | null |
138,679 | ord_dataset-3fa0a6b7d51b4fc6a5380aa0d03ac884 | null | 1985-01-01T00:12:00 | true | [NH2:1][C@@H:2]1[C:33](=[O:34])[N:4]2[C:5]([C:17]([O:19][CH:20]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[O:18])=[C:6]([CH2:9][S:10][C:11]3[N:15]([CH3:16])[N:14]=[N:13][N:12]=3)[CH2:7][S:8][C@H:3]12.[Br:35][C:36]([CH2:42][CH3:43])([CH:39]([Br:41])[CH3:40])[CH:37]=O.S([O-])([O-])(=O)=O.[Mg+2]>C(Cl)Cl>[Br:35][C:36]([CH2:42][CH3:43])([CH:39]([Br:41])[CH3:40])[CH:37]=[N:1][C@@H:2]1[C:33](=[O:34])[N:4]2[C:5]([C:17]([O:19][CH:20]([C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[O:18])=[C:6]([CH2:9][S:10][C:11]3[N:15]([CH3:16])[N:14]=[N:13][N:12]=3)[CH2:7][S:8][C@H:3]12 | CCC(Br)(C=O)C(C)Br | Cn1nnnc1SCC1=C(C(=O)OC(c2ccccc2)c2ccccc2)N2C(=O)[C@@H](N)[C@H]2SC1 | null | O=S(=O)([O-])[O-] | [Mg+2] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | 25 | 4 | To a solution of benzhydryl 7β-amino-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylate (2.47 g, 5.00 mmol) in methylene chloride (35 ml) was added under ice-cooling a solution of 2,3-dibromo-2-ethylbutanal (1.42 g, 5.50 mmol) in methylene chloride (5 ml) followed by addition of anhydrous magnesium sulfate. The resulting mixture was stirred at room temperature for 4 hours. The reaction mixture was filtered, the filtrate was concentrated under reduced pressure and, after addition of benzene (20 ml) and thorough stirring, insolubles were filtered off. The filtrate was concentrated to dryness under reduced pressure and the reside was made powdery by the addition of ether (10 ml). The resulting powder was recovered by filtration and dried under reduced pressure to give 3.12 g (85%) of the title compound as a pale brown powder. | CCC(Br)(C=N[C@@H]1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(CSc3nnnn3C)CS[C@H]12)C(C)Br | null | 85 | null |
1,064,818 | ord_dataset-ffbef48837674f39816de887b5dc8bae | null | 2011-01-01T00:06:00 | true | [C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]([C:32]([Cl:34])=[O:33])[C@H:13]([C:24]3[CH:29]=[CH:28][C:27]([C:30]#[CH:31])=[CH:26][CH:25]=3)[C@H:14]([C:16]3[CH:21]=[CH:20][C:19]([C:22]#[CH:23])=[CH:18][CH:17]=3)[N:15]=2)=[C:7]([O:35][CH2:36][CH3:37])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].Cl.Cl.[CH3:40][S:41]([CH2:44][CH2:45][N:46]1[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]1)(=[O:43])=[O:42]>>[ClH:34].[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]([C:32]([N:49]3[CH2:48][CH2:47][N:46]([CH2:45][CH2:44][S:41]([CH3:40])(=[O:42])=[O:43])[CH2:51][CH2:50]3)=[O:33])[C@H:13]([C:24]3[CH:29]=[CH:28][C:27]([C:30]#[CH:31])=[CH:26][CH:25]=3)[C@H:14]([C:16]3[CH:21]=[CH:20][C:19]([C:22]#[CH:23])=[CH:18][CH:17]=3)[N:15]=2)=[C:7]([O:35][CH2:36][CH3:37])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2] | C#Cc1ccc([C@@H]2[C@H](c3ccc(C#C)cc3)N=C(c3ccc(C(C)(C)C)cc3OCC)N2C(=O)Cl)cc1 | CS(=O)(=O)CCN1CCNCC1 | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | [(4S,5R)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-ethynyl-phenyl)-4,5-dihydro-imidazol-1-yl]-[4-(2-methanesulfonyl-ethyl)-piperazin-1-yl]-methanone hydrochloride was prepared from (4S,5R)-2-(4-tert-butyl-2-ethoxy-phenyl)-4,5-bis-(4-ethynyl-phenyl)-4,5-dihydro-imidazole-1-carbonyl chloride (example 12c) and 1-(2-methanesulfonylethyl)-piperazine dihydrochloride (example 17) in an analogous manner as described in example 25. LR-MS: 665.5 [(M+H)+] | C#Cc1ccc([C@@H]2[C@H](c3ccc(C#C)cc3)N=C(c3ccc(C(C)(C)C)cc3OCC)N2C(=O)N2CCN(CCS(C)(=O)=O)CC2)cc1 | null | null | null |
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