original_index int64 2 1.77M | extracted_from_file stringclasses 489 values | date_of_experiment timestamp[ns]date | grant_date timestamp[ns]date 1976-01-01 00:01:00 2016-01-01 00:09:00 | is_mapped bool 1 class | rxn_str stringlengths 87 6.12k | reactant_000 stringlengths 1 902 | reactant_001 stringlengths 1 902 ⌀ | reactant_002 null | agent_000 stringlengths 1 540 ⌀ | agent_001 stringlengths 1 852 ⌀ | agent_002 stringlengths 1 247 ⌀ | agent_003 null | agent_004 null | agent_005 null | agent_006 null | agent_007 null | agent_008 null | agent_009 null | agent_010 null | agent_011 null | agent_012 null | agent_013 null | agent_014 null | agent_015 null | agent_016 null | solvent_000 stringclasses 446 values | solvent_001 stringclasses 405 values | solvent_002 null | solvent_003 null | solvent_004 null | solvent_005 null | solvent_006 null | solvent_007 null | solvent_008 null | solvent_009 null | solvent_010 null | temperature float64 -230 30.1k ⌀ | rxn_time float64 0 2.16k ⌀ | procedure_details stringlengths 8 24.5k | product_000 stringlengths 1 484 | product_001 null | yield_000 float64 0 90,205,156,600B ⌀ | yield_001 float64 0 100M ⌀ |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1,396,313 | ord_dataset-12dc3bd21bcf44d09e5b4249afe15161 | null | 2014-01-01T00:02:00 | true | Cl.Cl[C:3]1[N:8]=[C:7]([C:9]2([C:13]([OH:15])=O)[CH2:12][CH2:11][CH2:10]2)[CH:6]=[CH:5][CH:4]=1.[CH3:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][CH2:25][NH2:26])=[CH:20][CH:19]=1.Cl.C(N=C=NCCCN(C)C)C>ClCCl.CN(C)C1C=CN=CC=1>[CH3:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][CH2:25][NH:26][C:13]([C:9]2([C:7]3[CH:6]=[CH:5][CH:4]=[CH:3][N:8]=3)[CH2:10][CH2:11][CH2:12]2)=[O:15])=[CH:20][CH:19]=1 | O=C(O)C1(c2cccc(Cl)n2)CCC1 | COc1ccc(CCN)cc1 | null | CCN=C=NCCCN(C)C | CN(C)c1ccncc1 | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | 25 | 0.5 | 1-(6-Chloropyridin-2-yl)cyclobutanecarboxylic acid hydrochloride (2.6 g, 10.48 mmol) was suspended in dichloromethane (30 ml). 2-(4-Methoxyphenyl)ethanamine (1.743 g, 11.53 mmol) and 4-dimethylaminopyridine (2.56 g, 20.96 mmol) were added and stirring at room temperature was continued for 30 min. The reaction mixture was cooled to 0° C. and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (2.21 g, 11.53 mmol) was added in small portions. The reaction mixture was allowed to warm to room temperature and stirring was continued over night. The reaction mixture was poured on water. The aqueous layer was extracted with dichloromethane (3×). The combined organic layers were washed with 5% aqueous citric acid and dried (MgSO4). The solvent was evaporated in vacuo and the crude product purified by flash chromatography (silica, heptane, ethyl acetate). Yield: 709 mg (2.056 mmol, 19.6%). | COc1ccc(CCNC(=O)C2(c3ccccn3)CCC2)cc1 | null | null | null |
1,389,378 | ord_dataset-31641fb65b34430fa7435229b949b604 | null | 2014-01-01T00:01:00 | true | [CH2:1](Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:9][C:10]1[CH:11]=[C:12]2[C:17](=[C:18]([C:20]([NH2:22])=[O:21])[CH:19]=1)[N:16]=[CH:15][N:14]=[C:13]2[NH:23][CH2:24][C:25]1[CH:30]=[CH:29][C:28]([Cl:31])=[C:27]([C:32]([F:35])([F:34])[F:33])[CH:26]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C(Cl)Cl>[CH2:1]([NH:9][C:10]1[CH:11]=[C:12]2[C:17](=[C:18]([C:20]([NH2:22])=[O:21])[CH:19]=1)[N:16]=[CH:15][N:14]=[C:13]2[NH:23][CH2:24][C:25]1[CH:30]=[CH:29][C:28]([Cl:31])=[C:27]([C:32]([F:34])([F:35])[F:33])[CH:26]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1 | NC(=O)c1cc(N)cc2c(NCc3ccc(Cl)c(C(F)(F)F)c3)ncnc12 | BrCc1ccccc1 | null | O=C([O-])[O-] | [Cs+] | 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 | 50 | 8 | Benzylbromide (140 μL, 0.5 M in anhydrous DCM, 0.07 mmol, 1.1 equiv.) was added to a solution of 6-amino-4-{[4-chloro-3-(trifluoromethyl)benzyl]amino}quinazoline-8-carboxamide (25 mg, 0.06 mmol, 1.0 equiv.) and cesium carbonate (62 mg, 0.19 mmol, 3.0 equiv.) in anhydrous DCM (2 mL). The resulting mixture was stirred at 50° C. overnight. The title compound was obtained by pre-HPLC in 17% yield. Mass: M+H+: 486. | NC(=O)c1cc(NCc2ccccc2)cc2c(NCc3ccc(Cl)c(C(F)(F)F)c3)ncnc12 | null | 17 | null |
28,967 | ord_dataset-2cb52357eb5f43c2be56ad5c0662f18f | null | 1977-01-01T00:08:00 | true | [CH3:1][N:2]([CH3:7])[S:3](Cl)(=[O:5])=[O:4].[NH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15](=[O:17])[CH3:16])=[CH:11][CH:10]=1.C>N1C=CC=CC=1>[C:15]([C:12]1[CH:13]=[CH:14][C:9]([NH:8][S:3]([N:2]([CH3:7])[CH3:1])(=[O:5])=[O:4])=[CH:10][CH:11]=1)(=[O:17])[CH3:16] | CC(=O)c1ccc(N)cc1 | CN(C)S(=O)(=O)Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | c1ccncc1 | null | null | null | null | null | null | null | null | null | null | 25 | 8 | Dimethylsulfamoyl chloride (14.4 g., 0.10 mole) is added dropwise to p-aminoacetophenone (13.5 g., 0.10 mole) in pyridine (60 ml.) at 10°-15° C. The mixture is stirred at room temperature overnight and then added to excess 6N HC1 to give 14.1 g. (58%) of solid. The solid is dissolved in base, treated with charcoal, reprecipitated with dil. HC1, and recrystallized from water-isopropanol to give 8.9 g. (37%) of the above pure intermediate, m.p. 129°-130° C. | CC(=O)c1ccc(NS(=O)(=O)N(C)C)cc1 | null | null | null |
891,799 | ord_dataset-11068b1e475b4c5b82e56726ab0dddb7 | null | 2009-01-01T00:07:00 | true | [CH2:1]([O:8][C:9]([N:11]([CH2:32][C:33]([N:35]1[CH2:39][C@@H:38]([F:40])[CH2:37][C@H:36]1[C:41]#[N:42])=[O:34])[C:12]12[CH2:19][CH2:18][C:15]([C:20](ON3C4C=CC=CC=4N=N3)=[O:21])([CH2:16][CH2:17]1)[CH2:14][CH2:13]2)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:43]([CH:50]1[CH2:55][CH2:54][NH:53][CH2:52][CH2:51]1)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>>[CH2:1]([O:8][C:9]([N:11]([CH2:32][C:33]([N:35]1[CH2:39][C@@H:38]([F:40])[CH2:37][C@H:36]1[C:41]#[N:42])=[O:34])[C:12]12[CH2:19][CH2:18][C:15]([C:20]([N:53]3[CH2:54][CH2:55][CH:50]([CH2:43][C:44]4[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=4)[CH2:51][CH2:52]3)=[O:21])([CH2:14][CH2:13]1)[CH2:16][CH2:17]2)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1 | c1ccc(CC2CCNCC2)cc1 | N#C[C@@H]1C[C@H](F)CN1C(=O)CN(C(=O)OCc1ccccc1)C12CCC(C(=O)On3nnc4ccccc43)(CC1)CC2 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | In a similar manner to Example 4, (2S,4S)-1-[[N-benzyloxycarbonyl-N-[4-(benzotriazol-1-yl)oxycarbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (50.0 mg) and 4-benzylpiperidine (22.9 μL) were used to obtain (2S,4S)-1-[[N-benzyloxycarbonyl-N-[4-(4-benzylpiperidin-1-yl)carbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (45.9 mg). | N#C[C@@H]1C[C@H](F)CN1C(=O)CN(C(=O)OCc1ccccc1)C12CCC(C(=O)N3CCC(Cc4ccccc4)CC3)(CC1)CC2 | null | null | null |
122,338 | ord_dataset-a9b95e50436441ff8f3f12dd60d1e1b2 | null | 1984-01-01T00:10:00 | true | [OH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[C:4]([O:11][CH3:12])[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:19](Br)[CH2:20][CH2:21][CH3:22].CN(C)C=O>O>[CH2:19]([O:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[C:4]([O:11][CH3:12])[CH:3]=1)[CH2:20][CH2:21][CH3:22] | CCCCBr | COc1cc(O)ccc1C(=O)O | null | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | null | A mixture of 4.2 g. (0.025 mole) of 4-hydroxy-2-methoxybenzoic acid, 7 g. of potassium carbonate, and 10 g. of n-butyl bromide in 100 ml. of N,N-dimethylformamide was heated at 70° C. for 24 hours. The mixture was cooled, diluted with water and extracted with diethyl ether. The ether extracts were washed with dilute sodium hydroxide solution, then washed with water and dried. The ether was evaporated and the residue heated at reflux for 4 hours in an equivolume mixture of 10 percent sodium hydroxide solution and ethanol. Evaporation followed by acidification provided the desired 4-(n-butoxy)-2-methoxy-benzoic acid (m.p. 94°-96° C. after recrystallizaiton from cyclohexane). | CCCCOc1ccc(C(=O)O)c(OC)c1 | null | null | null |
386,270 | ord_dataset-d330662edaed408d950898172aba7a4c | null | 1997-01-01T00:12:00 | true | [OH:1][CH2:2][C:3]([O:5][CH2:6][CH2:7][CH2:8][CH3:9])=[O:4].C(N(CC)CC)C.[CH3:17][S:18](Cl)(=[O:20])=[O:19]>ClCCl>[CH3:17][S:18]([O:1][CH2:2][C:3]([O:5][CH2:6][CH2:7][CH2:8][CH3:9])=[O:4])(=[O:20])=[O:19] | CS(=O)(=O)Cl | CCCCOC(=O)CO | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | CCN(CC)CC | null | null | null | null | null | null | null | null | null | 0 | 8 | 27.8 g (0.2 mol) of n-butyl hydroxyacetate (95% pure by GC) and 20.2 g (0.2 mol) of triethylamine are first introduced into 300 ml of dichloromethane at -5° C. 34.4 g (0.3 mol) of methanesulfonyl chloride in 50 ml of dichloromethane are slowly added dropwise at 0° to 5° C. Stirring of the batch at 0° C. is continued overnight, ice water is added, the phases are separated, and the aqueous phase is extracted twice with dichloromethane. The combined organic phases are dried, and the solvent is removed on a rotary evaporator leaving a colorless oil which is subjected to incipient distillation in vacuo. n-Butyl methylsulfonyloxyacetate is isolated as an almost colorless oil (40.5 g, 96.3% of theory, GC content 91%). | CCCCOC(=O)COS(C)(=O)=O | null | null | null |
81,694 | ord_dataset-f196f0a87dd74fcd82ca019f8ff5cf9c | null | 1981-01-01T00:05:00 | true | [C:1]([CH:11]1[O:17][CH:16]2[C:13]([C:27](=[O:35])[CH2:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)([C:14](=[O:26])[N:15]2[C:18](=[C:23]([CH3:25])[CH3:24])[C:19]([O:21][CH3:22])=[O:20])[NH:12]1)([O:3]CC1C=CC=CC=1)=[O:2]>O1CCCC1.[C].[Pd]>[C:1]([CH:11]1[O:17][CH:16]2[C:13]([C:27](=[O:35])[CH2:28][C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)([C:14](=[O:26])[N:15]2[C:18](=[C:23]([CH3:24])[CH3:25])[C:19]([O:21][CH3:22])=[O:20])[NH:12]1)([OH:3])=[O:2] | COC(=O)C(=C(C)C)N1C(=O)C2(C(=O)Cc3ccccc3)NC(C(=O)OCc3ccccc3)OC12 | null | null | [Pd] | 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 4.24 g of methyl α-(3ξ-carbobenzoxy-2-phenylacetyl-7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]heptan-6-yl)-α-isopropylideneacetate dissolved in 64 ml of tetrahydrofuran is catalytically hydrogenated on 1.3 g of 5% palladium carbon under atmospheric pressure. The catalyst is removed by filtration and the filtrate is condensed to yield 3.38 g of methyl α-(3ξ-carboxy-2-phenylacetyl-7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]heptan-6-yl)-α-isopropylideneacetate as crude product in quantitative yield. | COC(=O)C(=C(C)C)N1C(=O)C2(C(=O)Cc3ccccc3)NC(C(=O)O)OC12 | null | 98.2 | null |
1,708,305 | ord_dataset-54347fcace774f89850681d6dec8009f | null | 2016-01-01T00:03:00 | true | [Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([C@@H:21]([CH2:26][CH3:27])[CH:22]=[CH:23][C:24]#[N:25])[C:11](=[O:28])[C@@H:10]([CH2:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[H][H]>CCO.[Pd]>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([C@@H:21]([CH2:26][CH3:27])[CH2:22][CH2:23][C:24]#[N:25])[C:11](=[O:28])[C@@H:10]([CH2:29][C:30]([O:32][C:33]([CH3:34])([CH3:36])[CH3:35])=[O:31])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1 | CC[C@@H](C=CC#N)N1C(=O)[C@@H](CC(=O)OC(C)(C)C)C[C@H](c2cccc(Cl)c2)[C@H]1c1ccc(Cl)cc1 | [H][H] | 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 | 25 | 2 | To a solution of 56 mg (0.106 mmol) of tert-butyl 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-cyanopent-1-en-3-yl)-2-oxopiperidin-3-yl)acetate (Example 30, Step A) in 3.5 mL of EtOH) was added 10% palladium on activated carbon (11.30 mg, 10.62 μmol). Then the reaction mixture was subjected to regular hydrogenation with hydrogen. After being stirred under a hydrogen atmosphere at rt for 2 h, the catalyst was filtered using a short plug of silica gel. The plug was washed several times with EtOAc. The combined filtrates were concentrated under reduced pressure to provide the crude title compound as a colorless film which was used in the subsequent reaction without further purification. MS (ESI) 529.2 [M+H]+. | CC[C@@H](CCC#N)N1C(=O)[C@@H](CC(=O)OC(C)(C)C)C[C@H](c2cccc(Cl)c2)[C@H]1c1ccc(Cl)cc1 | null | null | null |
896,959 | ord_dataset-de6bce51790e4004a27e1a8f2bcc7ded | null | 2009-01-01T00:08:00 | true | CS([N:5]1[C:9]([CH3:10])=[CH:8][C:7]([NH:11][C:12]2[N:13]=[C:14]([CH2:24]OS(C)(=O)=O)[C:15]3[C:20]([CH:21]=2)=[CH:19][C:18]([O:22][CH3:23])=[CH:17][CH:16]=3)=[N:6]1)(=O)=O.[NH:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1.C([O-])([O-])=O.[K+].[K+]>C1COCC1.CCO>[CH3:23][O:22][C:18]1[CH:19]=[C:20]2[C:15](=[CH:16][CH:17]=1)[C:14]([CH2:24][N:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1)=[N:13][C:12]([NH:11][C:7]1[CH:8]=[C:9]([CH3:10])[NH:5][N:6]=1)=[CH:21]2 | COc1ccc2c(COS(C)(=O)=O)nc(Nc3cc(C)n(S(C)(=O)=O)n3)cc2c1 | C1CCNCC1 | null | O=C([O-])[O-] | [K+] | 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 | 120 | null | A 2.0˜5.0 mL process vial was charged with 50 mg methanesulfonic acid 3-(1-methanesulfonyl-5-methyl-1H-pyrazol-3-ylamino)-6-methoxy-isoquinolin-1-ylmethyl ester, 50 mg piperidine, 75 mg K2CO3 in 3 mL THF/EtOH(1:1). The vial was heated at 120° C. for 30 min under microwave irradiation. After cooling, the reaction mixture was filtered through a short silica gel column, and the solvent was removed under reduced pressure. The residue in MeOH was sent to prep-HPLC to get 5 mg of (6-Methoxy-1-piperidin-1-ylmethyl-isoquinolin-3-yl)-(5-methyl-1H-pyrazol-3-yl)-amine as a yellow solid. LC-MS m/e 352 (MH+). | COc1ccc2c(CN3CCCCC3)nc(Nc3cc(C)[nH]n3)cc2c1 | null | 12.5 | null |
237,702 | ord_dataset-56e7a343b17a4d6da818127ceb19589d | null | 1991-01-01T00:11:00 | true | [NH2:1][C:2]1[S:3][C:4]2[CH2:5][CH2:6][NH:7][CH2:8][CH2:9][C:10]=2[N:11]=1.C(=O)([O-])[O-].[K+].[K+].[Br:18][C:19]1[CH:28]=[CH:27][CH:26]=[CH:25][C:20]=1[CH:21]=[CH:22][CH2:23]Br.C(OC(C)C)(C)C>CN(C)C=O>[NH2:1][C:2]1[S:3][C:4]2[CH2:5][CH2:6][N:7]([CH2:23][CH:22]=[CH:21][C:20]3[CH:25]=[CH:26][CH:27]=[CH:28][C:19]=3[Br:18])[CH2:8][CH2:9][C:10]=2[N:11]=1 | Nc1nc2c(s1)CCNCC2 | BrCC=Cc1ccccc1Br | null | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | CC(C)OC(C)C | null | null | null | null | null | null | null | null | null | null | null | Prepared analogously to Example 1 from 2-amino-4,5,7,8-tetrahydro-6H-thiazolo[5,4-d]azepine, potassium carbonate and 2-bromo-cinnamyl bromide in anhydrous dimethylformamide for 2 hours at 20° C. Yield: 42% of theory, Melting point: 103°-106° C. (diisopropylether). | Nc1nc2c(s1)CCN(CC=Cc1ccccc1Br)CC2 | null | 42 | null |
1,236,356 | ord_dataset-e96f5a2842f14e5380461c234100f05a | null | 2012-01-01T00:12:00 | true | [Cl:1][C:2]1[CH:8]=[C:7]([OH:9])[C:6]([CH3:10])=[CH:5][C:3]=1[NH2:4].C(=O)([O-])[O-].[K+].[K+].[Cl:17][C:18]1([C:21]2[N:25]=[C:24](S(C3C=CC(C)=CC=3)(=O)=O)[S:23][N:22]=2)[CH2:20][CH2:19]1>C(#N)C>[Cl:1][C:2]1[CH:8]=[C:7]([O:9][C:24]2[S:23][N:22]=[C:21]([C:18]3([Cl:17])[CH2:20][CH2:19]3)[N:25]=2)[C:6]([CH3:10])=[CH:5][C:3]=1[NH2:4] | Cc1ccc(S(=O)(=O)c2nc(C3(Cl)CC3)ns2)cc1 | Cc1cc(N)c(Cl)cc1O | null | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC#N | null | null | null | null | null | null | null | null | null | null | 25 | 0.5 | 3.00 g (19.04 mmol) of 2-chloro-4-hydroxy-5-methylaniline are introduced into 50 ml of acetonitrile, treated at ambient temperature with 3.16 g (22.84 mmol) of potassium carbonate and stirred at ambient temperature for 30 min. Subsequently, 6.26 g (19.04 mmol) of 3-(1-chlorocyclopropyl)-5-[(4-methylphenyl]sulphonyl]-1,2,4-thiadiazole are added and the reaction mixture is stirred at 50° C. for 12 h. After cooling, the mixture is concentrated on a rotary evaporator, the residue is taken up in dichloromethane and the solution is extracted twice with water, dried over Na2SO4 and freed from solvent under vacuum. The residue is purified by column chromatography. 3.18 g of product are obtained (93.3% purity, 49.4% yield, log P (pH 2.3)=3.50). | Cc1cc(N)c(Cl)cc1Oc1nc(C2(Cl)CC2)ns1 | null | 52.8 | null |
1,561,136 | ord_dataset-4e54080057a44c3887653391e24c90b6 | null | 2015-01-01T00:03:00 | true | Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=2)[CH:5]=[CH:4][CH:3]=1.[CH2:17]([CH2:20][OH:21])[CH2:18][NH2:19]>>[CH3:16][O:15][C:12]1[CH:13]=[CH:14][C:9]([NH:8][C:6]2[N:7]=[C:2]([NH:19][CH2:18][CH2:17][CH2:20][OH:21])[CH:3]=[CH:4][CH:5]=2)=[CH:10][CH:11]=1 | NCCCO | COc1ccc(Nc2cccc(Cl)n2)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 | 95 mg of 6-chloro-N-(4-methoxyphenyl)pyridin-2-amine were mixed with 244 mg of n-propanolamine and the mixture obtained was treated in a vial analogously to the method as set out in Example 16b. 3-(6-(4-Methoxyphenylamino)pyridin-2-ylamino)propan-1-ol was obtained in the form of a brown oil. | COc1ccc(Nc2cccc(NCCCO)n2)cc1 | null | 64 | null |
956,804 | ord_dataset-ed65749688da45af8a8432967b017729 | null | 2010-01-01T00:05:00 | true | C([O:3][CH:4](OCC)[CH2:5][N:6]([CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][O:25][CH2:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:7](=[O:19])[CH2:8][CH2:9][O:10][CH2:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)C.Cl.ClCCl>O1CCOCC1>[O:3]=[CH:4][CH2:5][N:6]([CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][O:25][CH2:26][CH2:27][C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)[C:7](=[O:19])[CH2:8][CH2:9][O:10][CH2:11][CH2:12][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1 | CCOC(CN(CCCCCOCCc1ccccc1)C(=O)CCOCCc1ccccc1)OCC | null | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1COCCO1 | ClCCl | null | null | null | null | null | null | null | null | null | null | null | N-(2,2-Diethoxyethyl)-3-phenethyloxy-N-(5-phenethyloxypentyl)propanamide (Example 9b), 0.18 g) was dissolved in anhydrous dioxane (5 mL) and treated with concentrated hydrochloric acid (5 mL) at room temperature. The resultant solution was stirred for 1 hour and then poured into dichloromethane (10 mL), washed with water (2×10 mL) and brine (10 mL). The organic layer was isolated, dried over anhydrous magnesium sulphate, filtered and concentrated to give the sub-titled compound (0.12 g) as a viscous oil. | O=CCN(CCCCCOCCc1ccccc1)C(=O)CCOCCc1ccccc1 | null | null | null |
581,820 | ord_dataset-60f3171f0342452f8814e7f294e2be8b | null | 2003-01-01T00:02:00 | true | [Cl:1][CH2:2][C:3]1[CH:4]=[CH:5][C:6]2[S:11][C:10]3[N:12]=[CH:13][CH:14]=[N:15][C:9]=3[N:8](COC)[C:7]=2[CH:19]=1.Cl>O1CCCC1>[Cl:1][CH2:2][C:3]1[CH:4]=[CH:5][C:6]2[S:11][C:10]3[N:12]=[CH:13][CH:14]=[N:15][C:9]=3[NH:8][C:7]=2[CH:19]=1 | COCN1c2cc(CCl)ccc2Sc2nccnc21 | null | 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 | 25 | 0.5 | 6 g of 8-chloromethyl-10-methoxymethyl-10H-pyrazino[2,3-b][1,4]benzothiazine was dissolved in 50 ml of tetrahydrofuran and 20 ml of 6 N hydrochloric acid was added thereto at 0° C. After stirring at room temperature for 30 minutes, the reaction mixture was poured into ice-water and extracted with ethyl acetate. The extract was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The crystals precipitating in the course of the concentration were taken up by filtration and washed with diethyl ether to thereby give 4.8 g of the title compound as yellow crystals. | ClCc1ccc2c(c1)Nc1nccnc1S2 | null | 94.1 | null |
1,492,221 | ord_dataset-366bdd9ee72d474cbe6f3f9e54dd96d2 | null | 2014-01-01T00:10:00 | true | [Cl:1][C:2]1[CH:3]=[C:4](B2OC(C)(C)C(C)(C)O2)[CH:5]=[C:6]([Cl:14])[C:7]=1[O:8][CH2:9][C:10]([F:13])([F:12])[F:11].Br[C:25]([C:27]([F:30])([F:29])[F:28])=[CH2:26].C([O-])([O-])=O.[K+].[K+]>C1COCC1.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:14][C:6]1[CH:5]=[C:4]([C:25]([C:27]([F:30])([F:29])[F:28])=[CH2:26])[CH:3]=[C:2]([Cl:1])[C:7]=1[O:8][CH2:9][C:10]([F:11])([F:12])[F:13] | CC1(C)OB(c2cc(Cl)c(OCC(F)(F)F)c(Cl)c2)OC1(C)C | C=C(Br)C(F)(F)F | null | Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1 | O=C([O-])[O-] | [K+] | 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 | 80 | null | A mixture of 2-(3,5-dichloro-4-(2,2,2-trifluoroethoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (530 mg, 1.43 mmol), 2-bromo-3,3,3-trifluoroprop-1-ene (275 mg, 1.57 mmol), K2CO3 (395 mg, 2.86 mmol) and Pd(PPh3)2Cl2 (20 mg, 0.029 mmol) in THF (3 mL) and H2O (3 mL) was heated at 80° C. in a sealed tube for 3 h. The mixture was cooled to rt and partitioned between EA (50 mL) and H2O (50 mL). The aqueous layer was extracted with EA (50 mL) and the combined organic layers were dried over Na2SO4. The solvent was removed under reduced pressure and the crude product was purified by column chromatography on silica gel elute with PE to give 1,3-dichloro-2-(2,2,2-trifluoroethoxy)-5-(3,3,3-trifluoroprop-1-en-2-yl)benzene (360 mg; yield 74%) as colorless oil. | C=C(c1cc(Cl)c(OCC(F)(F)F)c(Cl)c1)C(F)(F)F | null | 74.2 | null |
1,162,712 | ord_dataset-d24cc23b3db94284bb83a2ccdd9eb880 | null | 2012-01-01T00:05:00 | true | [F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:12]([CH2:13][OH:14])=[C:11]([CH3:15])[O:10][N:9]=2)=[N:6][CH:7]=1.[CH3:16][O:17][C:18]([C:20]1[S:24][N:23]=[C:22](O)[CH:21]=1)=[O:19].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[CH3:16][O:17][C:18]([C:20]1[S:24][N:23]=[C:22]([O:14][CH2:13][C:12]2[C:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][N:6]=3)=[N:9][O:10][C:11]=2[CH3:15])[CH:21]=1)=[O:19] | COC(=O)c1cc(O)ns1 | Cc1onc(-c2ccc(F)cn2)c1CO | null | CCOC(=O)N=NC(=O)OCC | c1ccc(P(c2ccccc2)c2ccccc2)cc1 | 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 | To a solution of [3-(5-fluoro-pyridin-2-yl)-5-methyl-isoxazol-4-yl]-methanol (458 mg, 2.2 mmol) in THF (10 mL) was added 3-hydroxy-isothiazole-5-carboxylic acid methyl ester (350 mg, 1.9 mmol) and triphenylphosphine (692 mg, 2.6 mmol) at 0° C. under an argon atmosphere. Then diethyl azodicarboxylate (˜40% in toluene, 1.05 mL, 2.4 mmol) was added and the reaction mixture was stirred overnight at room temperature. Concentration and purification by chromatography (silica, heptane:ethyl acetate=4:1 to 0:1) afforded the title compound (488 mg, 64%) as a white solid. MS: m/e=350.1 [M+H]+. | COC(=O)c1cc(OCc2c(-c3ccc(F)cn3)noc2C)ns1 | null | 73.5 | null |
1,607,603 | ord_dataset-9cecb3a8d3b9494191b28dcefea66af2 | null | 2015-01-01T00:07:00 | true | [Br:1][C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]([Cl:15])[CH:10]=2)[C:5]([N+:16]([O-])=O)=[CH:4][CH:3]=1.[Cl-].[NH4+]>CO.C1COCC1.[Zn]>[Br:1][C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]([Cl:15])[CH:10]=2)[C:5]([NH2:16])=[CH:4][CH:3]=1 | O=[N+]([O-])c1ccc(Br)nc1Nc1ccnc(Cl)c1 | null | null | [Cl-] | [NH4+] | [Zn] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | CO | null | null | null | null | null | null | null | null | null | 25 | 0.08 | (6-Bromo-3-nitro-pyridin-2-yl)-(2-chloro-pyridin-4-yl)amine (step 1) (1 eq, 0.303 mmol, 100 mg) is dissolved in MeOH/THF (6 ml of a 1:1 mixture) and stirred for 5 minutes at RT. Zinc (22 eq, 6.6 mmol 350 mg) is added and the reaction mixture is stirred for a further 20 minutes. Saturated aqueous ammonium chloride (0.8 ml) is added to the reaction mixture and stirring continued at room temperature for 30 minutes. The mixture is filtered through CELITE® and the filtrate is diluted with water (10 ml) and extracted with EtOAc (2×10 ml). The organic portions are combined, dried (MgSO4) and concentrated in vacuo to afford the title compound; [M+H]+300. | Nc1ccc(Br)nc1Nc1ccnc(Cl)c1 | null | null | null |
1,444,930 | ord_dataset-275a3da8f45f4536ad29727f0ef9ba66 | null | 2014-01-01T00:06:00 | true | C[O:2][C:3](=[O:30])[C@H:4]([NH:6][C:7]([C:9]1[CH:29]=[CH:28][C:12]2[N:13]([CH3:27])[C:14]([NH:16][C:17]3[S:18][C:19]4[CH:25]=[C:24]([Cl:26])[CH:23]=[CH:22][C:20]=4[N:21]=3)=[N:15][C:11]=2[CH:10]=1)=[O:8])[CH3:5].[OH-].[Li+]>>[Cl:26][C:24]1[CH:23]=[CH:22][C:20]2[N:21]=[C:17]([NH:16][C:14]3[N:13]([CH3:27])[C:12]4[CH:28]=[CH:29][C:9]([C:7]([NH:6][C@H:4]([CH3:5])[C:3]([OH:30])=[O:2])=[O:8])=[CH:10][C:11]=4[N:15]=3)[S:18][C:19]=2[CH:25]=1 | COC(=O)[C@@H](C)NC(=O)c1ccc2c(c1)nc(Nc1nc3ccc(Cl)cc3s1)n2C | null | null | [Li+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | (R)-2-{[2-(6-Chloro-benzothiazol-2-ylamino)-1-methyl-1H-benzoimidazole-5-carbonyl]-amino}-propionic acid (341 mg) was prepared by following General Procedure E starting from (R)-2-{[2-(6-chloro-benzothiazol-2-ylamino)-1-methyl-1H-benzoimidazole-5-carbonyl]-amino}-propionic acid methyl ester (475 mg) and lithium hydroxide (180 mg). | C[C@@H](NC(=O)c1ccc2c(c1)nc(Nc1nc3ccc(Cl)cc3s1)n2C)C(=O)O | null | 74.1 | null |
1,766,480 | ord_dataset-0b32b90cc77b4a3db47ad263e0bbc1a8 | null | 2016-01-01T00:09:00 | true | O[C:2]1[C:3]2[N:11]=[CH:10][CH:9]=[C:8]([C:12]([NH2:14])=[O:13])[C:4]=2[N:5]=[CH:6][N:7]=1.Cl.[N:16]1([CH2:20][C@@H:21]([NH2:32])[C:22]2[CH:27]=[CH:26][C:25]([F:28])=[C:24]([CH:29]([F:31])[F:30])[CH:23]=2)[CH2:19][CH2:18][CH2:17]1>>[N:16]1([CH2:20][C@@H:21]([NH:32][C:2]2[C:3]3[N:11]=[CH:10][CH:9]=[C:8]([C:12]([NH2:14])=[O:13])[C:4]=3[N:5]=[CH:6][N:7]=2)[C:22]2[CH:27]=[CH:26][C:25]([F:28])=[C:24]([CH:29]([F:30])[F:31])[CH:23]=2)[CH2:19][CH2:18][CH2:17]1 | NC(=O)c1ccnc2c(O)ncnc12 | N[C@H](CN1CCC1)c1ccc(F)c(C(F)F)c1 | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Compound 48 was prepared following general synthesis scheme 7 wherein 4-hydroxypyrido[3,2-d]pyrimidine-8-carboxamide (G) was reacted with (S)-2-Azetidin-1-yl-1-(3-difluoromethyl-4-fluoro-phenyl)-ethylamine hydrochloride to give the title compound as a white solid. LC/MS [409 (M+H)]; 1H NMR (400 MHz, DMSO-d6) δ 9.93 (s, 1H), 9.09 (d, 1H), 9.02 (d, 1H), 8.55 (s, 1H), 8.39 (d, 1H), 8.18 (s, 1H), 7.58 (t, 1H), 7.52 (d, 1H), 7.45 (d, 1H), 7.29 (s, 1H), 7.16 (s, 1H), 7.02 (s, 1H), 5.34 (dd, 1H), 3.20-3.02 (m, 4H), 2.84 (dd, 2H), 1.99-1.85 (m, 2H). | NC(=O)c1ccnc2c(N[C@H](CN3CCC3)c3ccc(F)c(C(F)F)c3)ncnc12 | null | null | null |
1,735,888 | ord_dataset-eacfee6d16d8455a93348409f1b37be4 | null | 2016-01-01T00:06:00 | true | [H-].[Na+].[C:3](#[N:7])[CH2:4][C:5]#[N:6].Br[C:9]([C:15]1[N:16]=[C:17]([CH3:20])[O:18][CH:19]=1)([CH3:14])[C:10]([O:12][CH3:13])=[O:11]>CN(C=O)C>[C:5]([CH:4]([C:3]#[N:7])[C:9]([CH3:14])([C:15]1[N:16]=[C:17]([CH3:20])[O:18][CH:19]=1)[C:10]([O:12][CH3:13])=[O:11])#[N:6] | COC(=O)C(C)(Br)c1coc(C)n1 | N#CCC#N | 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 | 0.25 | To NaH (60%, 0.293 g, 7.32 mmol) in 10 mL of DMF at room temperature was added dropwise malononitrile (0.483 g, 7.32 mmol) in 5 mL of DMF. After stirring at room temperature for 15 minutes, the intermediate from Step C (1.82 g, 7.32 mmol) in 10 mL of DMF was added. The resulting mixture was stirred for 2 hours and then quenched with water. The mixture was extracted with EtOAc, dried with MgSO4, and concentrated. The residue was purified by silica gel chromatography using a hexanes/EtOAc gradient to give the indicated compound (a pale yellow oil). 1H NMR (CDCl3, 500 MHz) δ 7.66 (1H, s), 4.88 (1H, s), 3.87 (3H, s), 2.49 (3H, s), 1.92 (3H, s). m/z=234 (M+H). | COC(=O)C(C)(c1coc(C)n1)C(C#N)C#N | null | null | null |
854,468 | ord_dataset-faa0236be76c4501841c954527cd1b6c | null | 2008-01-01T00:12:00 | true | [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@@H:9]([NH:27]C(=O)OC(C)(C)C)[C:10](=[O:26])[NH:11][C:12]2[CH:13]=[C:14]3[C:24](=[O:25])[NH:23][N:22]=[CH:21][C:16]4=[CH:17][NH:18][C:19]([CH:20]=2)=[C:15]34)=[CH:4][CH:3]=1.[ClH:35]>O1CCOCC1>[ClH:35].[NH2:27][C@H:9]([CH2:8][C:5]1[CH:6]=[CH:7][C:2]([OH:1])=[CH:3][CH:4]=1)[C:10]([NH:11][C:12]1[CH:13]=[C:14]2[C:24](=[O:25])[NH:23][N:22]=[CH:21][C:16]3=[CH:17][NH:18][C:19]([CH:20]=1)=[C:15]23)=[O:26] | CC(C)(C)OC(=O)N[C@H](Cc1ccc(O)cc1)C(=O)Nc1cc2c3c(c[nH]c3c1)C=NNC2=O | null | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1COCCO1 | null | null | null | null | null | null | null | null | null | null | null | null | Preparation of example 178 from the title compound of Example 155 (90 mg, 0.194 mmol) and 4M HCl in dioxane (10 mL) was carried out analogously to Example 91. Isolation, also in an analogous manner afforded the title compound (56 mg, 0.140 mmol) as an orange/yellow powder in 72% yield. | N[C@H](Cc1ccc(O)cc1)C(=O)Nc1cc2c3c(c[nH]c3c1)C=NNC2=O | null | 72 | null |
620,234 | ord_dataset-2952e63264f5422a84e12cca1e0541ee | null | 2003-01-01T00:12:00 | true | [OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[C:4]([OH:12])[CH:3]=1.Cl.[CH3:14]O>>[CH3:14][O:12][C:4]1[CH:3]=[C:2]([OH:1])[C:11]2[C:6]([CH:5]=1)=[CH:7][CH:8]=[CH:9][CH:10]=2 | Oc1cc(O)c2ccccc2c1 | CO | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | 25 | 24 | To a stirring solution of 1,3-dihydroxynaphthalene (2.31 g, 14.4 mmol) in methanol (150 mL) at 0° C., hydrochloride gas was bubbed for 10 min. The resulting solution was continued stirring at room temperature for 24 hrs. A residue was obtained after evaporation of methanol and purified by silica gel column chromatography eluted with chloroform to provide the title compound as purple crystals (1.42 g, 57%). 1H NMR(300 MHz CDCl3) δ8.08(d, 1H), 7.70(d, 1H), 7.46(t, 1H), 7.34(t, 1H), 6.78 (s, 1H), 6.54 (s, 1H), 5.61(s, 1H), 3.90(s, 3H). | COc1cc(O)c2ccccc2c1 | null | 57 | null |
209,511 | ord_dataset-ac1c7aa04d6c4e588e723e3e05721681 | null | 1990-01-01T00:05:00 | true | [C:1]([N:4]1[CH2:9][CH:8]=[C:7]([C:10]2[C:15]([F:16])=[CH:14][C:13]([C:17](=[O:28])[C:18](=[CH:24]OCC)[C:19]([O:21][CH2:22][CH3:23])=[O:20])=[C:12]([F:29])[CH:11]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[CH:30]1([NH2:33])[CH2:32][CH2:31]1>C(OCC)C>[C:1]([N:4]1[CH2:9][CH:8]=[C:7]([C:10]2[C:15]([F:16])=[CH:14][C:13]([C:17](=[O:28])[C:18](=[CH:24][NH:33][CH:30]3[CH2:32][CH2:31]3)[C:19]([O:21][CH2:22][CH3:23])=[O:20])=[C:12]([F:29])[CH:11]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2] | NC1CC1 | CCOC=C(C(=O)OCC)C(=O)c1cc(F)c(C2=CCN(C(C)=O)CC2)cc1F | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOCC | null | null | null | null | null | null | null | null | null | null | null | 22 | A solution of 4.50 g (11.06 mmol) of ethyl 4-(1-acetyl-1,2,3,6-tetrahydro-4-pyridyl)-α-(ethoxymethylene)-2,5-difluoro-β-oxobenzenepropionate in 50 ml of ethyl ether was treated with 0.77 g (13.5 mmol) of cyclopropylamine and stirred for 22 hours. The title compound was isolated as a syrup after evaporation under vacuum. | CCOC(=O)C(=CNC1CC1)C(=O)c1cc(F)c(C2=CCN(C(C)=O)CC2)cc1F | null | null | null |
963,389 | ord_dataset-ed65749688da45af8a8432967b017729 | null | 2010-01-01T00:05:00 | true | [CH:1]1([C:7]2[N:12]=[N:11][C:10]([C:13]3[CH:54]=[CH:53][C:16]([CH2:17][C:18]4[N:19]([C:31]5[CH:32]=[C:33]([N:37]6[S:41](=[O:43])(=[O:42])[N:40](COCC[Si](C)(C)C)[C:39](=[O:52])[CH2:38]6)[CH:34]=[CH:35][CH:36]=5)[CH:20]=[C:21]([C:23]5[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][C:24]=5[Cl:30])[N:22]=4)=[CH:15][CH:14]=3)=[CH:9][CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>>[CH:1]1([C:7]2[N:12]=[N:11][C:10]([C:13]3[CH:54]=[CH:53][C:16]([CH2:17][C:18]4[N:19]([C:31]5[CH:32]=[C:33]([N:37]6[S:41](=[O:43])(=[O:42])[NH:40][C:39](=[O:52])[CH2:38]6)[CH:34]=[CH:35][CH:36]=5)[CH:20]=[C:21]([C:23]5[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][C:24]=5[Cl:30])[N:22]=4)=[CH:15][CH:14]=3)=[CH:9][CH:8]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1 | C[Si](C)(C)CCOCN1C(=O)CN(c2cccc(-n3cc(-c4ccc(Cl)cc4Cl)nc3Cc3ccc(-c4ccc(C5CCCCC5)nn4)cc3)c2)S1(=O)=O | null | null | CCCC[N+](CCCC)(CCCC)CCCC | [F-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | 5-{3-[2-[4-(6-Cyclohexyl-pyridazin-3-yl)-benzyl]-4-(2,4-dichloro-phenyl)-imidazol-1-yl]-phenyl}-1,1-dioxo-2-(2-trimethylsilanyl-ethoxymethyl)-[1,2,5]thiadiazolidin-3-one (16 mg, 0.02 mmol) was treated as described in general procedure W using tetrabutylammonium fluoride (26 mg, 0.1 mmol) to give 5-{3-[2-[4-(6-cyclohexyl-pyridazin-3-yl)-benzyl]-4-(2,4-dichloro-phenyl)-imidazol-1-yl]-phenyl}-1,2,5-thiadiazolidine-3-one-1,1-dioxide. | O=C1CN(c2cccc(-n3cc(-c4ccc(Cl)cc4Cl)nc3Cc3ccc(-c4ccc(C5CCCCC5)nn4)cc3)c2)S(=O)(=O)N1 | null | null | null |
924,401 | ord_dataset-cc0899cd744f4f7f8e7f2463560faad1 | null | 2009-01-01T00:12:00 | true | [Br:1][C:2]1[CH:3]=[CH:4][C:5]([OH:25])=[C:6]([CH:24]=1)[C:7]([NH:9][C:10]1[CH:15]=[C:14]([C:16]([CH3:19])([CH3:18])[CH3:17])[CH:13]=[C:12]([C:20]([CH3:23])([CH3:22])[CH3:21])[CH:11]=1)=[O:8].[N:26]1([C:32](Cl)=[O:33])[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:25][C:32]([N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)=[O:33])=[C:6]([CH:24]=1)[C:7]([NH:9][C:10]1[CH:15]=[C:14]([C:16]([CH3:17])([CH3:18])[CH3:19])[CH:13]=[C:12]([C:20]([CH3:23])([CH3:22])[CH3:21])[CH:11]=1)=[O:8] | CC(C)(C)c1cc(NC(=O)c2cc(Br)ccc2O)cc(C(C)(C)C)c1 | O=C(Cl)N1CCOCC1 | null | null | null | null | null | null | null | 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 5-bromo-N-{3,5-bis[(1,1-dimethyl)ethyl]phenyl}-2-hydroxybenzamide and morpholine-4-carbonyl chloride as the raw materials, the same operation as the example 71 gave the title compound. | CC(C)(C)c1cc(NC(=O)c2cc(Br)ccc2OC(=O)N2CCOCC2)cc(C(C)(C)C)c1 | null | 93.6 | null |
1,077,376 | ord_dataset-afd812677c134591a99f46ce28de2524 | null | 2011-01-01T00:08:00 | true | [C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([CH2:20][SH:21])=[C:16]([Cl:19])[CH:17]=[CH:18][C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[C:23]1[CH:28]=[CH:27][C:26]([C:29]2[N:30]=[C:31]([NH:34][CH2:35][CH:36]3[CH2:38][CH2:37]3)[S:32][CH:33]=2)=[CH:25][CH:24]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(N(C(C)C)CC)(C)C>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([CH2:20][S:21][C:23]3[CH:24]=[CH:25][C:26]([C:29]4[N:30]=[C:31]([NH:34][CH2:35][CH:36]5[CH2:37][CH2:38]5)[S:32][CH:33]=4)=[CH:27][CH:28]=3)=[C:16]([Cl:19])[CH:17]=[CH:18][C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3] | CC(C)(C)OC(=O)N1CCc2ccc(Cl)c(CS)c2CC1 | Brc1ccc(-c2csc(NCC3CC3)n2)cc1 | null | [Pd] | CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21 | O=C(/C=C/c1ccccc1)/C=C/c1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1COCCO1 | CCN(C(C)C)C(C)C | null | null | null | null | null | null | null | null | null | 100 | null | To a solution of 3-tert-butoxycarbonyl-7-chloro-6-mercaptomethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.051 g, 0.155 mmol) in dry dioxane (0.7 mL) add N-[4-(4-bromo-phenyl)-thiazol-2-yl]-cyclopropylmethylamine (0.043 g, 0.14 mmol), tris(dibenzylideneacetone)dipalladium(0) (3.2 mg, 0.0035 mmol), Xantphos (4.1 mg, 0.014 mmol) and diisopropylethylamine (0.049 mL, 0.28 mmol) at room temperature. Purge the reaction mixture with nitrogen and heat the mixture at 100° C. overnight. Cool the reaction mixture to room temperature, dilute with DCM (50 mL) and filter through Celite®. Concentrate the filtrate in vacuo. Dissolve the residue in DCM, load the solution on to a RediSep® column (40 g) and purify the crude mixture by preparative liquid chromatography (0:100 to 25:75 EtOAc/hexane over 33 min; 35 mL/min) to afford 3-tert-butoxycarbonyl-7-chloro-6-{4-[2-(cyclopropylmethyl-amino)-thiazol-4-yl]-phenylthiomethyl}-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.076 g, 97%) as a colorless oil. | CC(C)(C)OC(=O)N1CCc2ccc(Cl)c(CSc3ccc(-c4csc(NCC5CC5)n4)cc3)c2CC1 | null | 97.6 | null |
702,879 | ord_dataset-c408dfed796e4354b61e312e67f7143f | null | 2006-01-01T00:04:00 | true | [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][N:11]=[CH:10][C:9]=2[CH2:13][CH2:14][C:15](OC)=[O:16])=[CH:4][C:3]=1[F:19].[H-].C([Al+]CC(C)C)C(C)C.Cl>O1CCCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][N:11]=[CH:10][C:9]=2[CH2:13][CH2:14][CH2:15][OH:16])=[CH:4][C:3]=1[F:19] | COC(=O)CCc1cnoc1-c1ccc(Cl)c(F)c1 | null | null | CC(C)C[Al+]CC(C)C | Cl | [H-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | 25 | 1 | To a solution of methyl 3-[5-(4-chloro-3-fluorophenyl)-4-isoxazolyl]propionate (3.30 g) in tetrahydrofuran (30 ml) was gently added diisobutylaluminum hydride (1.0 M hexane solution, 25 ml) at 0° C., and the mixture was stirred at room temperature for 1 hr. The reaction mixture was poured into dilute hydrochloric acid, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, and 3-[5-(4-chloro-3-fluorophenyl)-4-isoxazolyl]propan-1-ol (2.79 g, yield 94%) was obtained as colorless crystals from a fraction eluted with ethyl acetate-hexane (2:1, volume ratio). The crystals were recrystallized from ethyl acetate-hexane. melting point: 51–52° C. | OCCCc1cnoc1-c1ccc(Cl)c(F)c1 | null | 93.8 | null |
200,547 | ord_dataset-31f00a039ca0424788e5e1970d25a8fd | null | 1989-01-01T00:12:00 | true | [CH:1]1([S:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[NH:14][S:15]([CH2:18][CH3:19])(=[O:17])=[O:16])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[N+:20]([O-])([OH:22])=[O:21].C(=O)([O-])O.[Na+]>C(O)(=O)C>[CH:1]1([S:7][C:8]2[CH:13]=[C:12]([N+:20]([O-:22])=[O:21])[CH:11]=[CH:10][C:9]=2[NH:14][S:15]([CH2:18][CH3:19])(=[O:17])=[O:16])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1 | CCS(=O)(=O)Nc1ccccc1SC1CCCCC1 | O=[N+]([O-])O | null | O=C([O-])O | [Na+] | 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 | 0 | null | In 20 ml of acetic acid was dissolved 1.5 g of N-[2-(cyclohexylthio)phenyl]ethanesulfonamide, 0.33 g of 61% nitric acid was added dropwise on heating at 80°-85° C., and then the mixture was stirred on heating for 1 hour. The reaction solution was poured into ice water, neutralized with a saturated sodium hydrogen carbonate solution and extracted with dichloromethane. The dichloromethane layer was washed, in turn, with a saturated aqueous sodium hydrogen carbonate solution, water and a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the resulting crude crystals were purified by silica gel column chromatography (eluent: n-hexane:dichloromethane:ethyl acetate=20:10:1) and recrystallized from carbon tetrachloride-n-hexane to give 1.1 g of N-(2-cyclohexylthio-4-nitrophenyl)ethanesulfonamide. | CCS(=O)(=O)Nc1ccc([N+](=O)[O-])cc1SC1CCCCC1 | null | 63.8 | null |
595,299 | ord_dataset-278fb6af8a994ac69e4d95e6e6eff756 | null | 2003-01-01T00:05:00 | true | CO[CH2:3][C:4](=[C:6]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[CH2:10][CH2:9][C:8]2[CH:17]=[CH:18][CH:19]=[CH:20][C:7]1=2)[CH3:5].[BrH:21]>C(O)(=O)C.O>[CH3:5][C:4](=[C:6]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[CH2:10][CH2:9][C:8]2[CH:17]=[CH:18][CH:19]=[CH:20][C:7]1=2)[CH2:3][Br:21] | COCC(C)=C1c2ccccc2CCc2ccccc21 | Br | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CC(=O)O | null | null | null | null | null | null | null | null | null | null | null | The above ether (3.6 g, 13.6 mmol) was dissolved in acetic acid (40 ml) and 48% hydrobromic acid (20 ml) was added. After 7 days the mixture was diluted with water (200 ml) and extracted with benzene (100 ml). The organic phase was dried (MgSO4), filtered and the solvent was evaporated in vacuo to give 3.8 g of crude 5-(1-methyl-2-bromoethylidene)-10,11-dihydro-5H-dibenzo[a,d]cycloheptene. | CC(CBr)=C1c2ccccc2CCc2ccccc21 | null | null | null |
814,765 | ord_dataset-50f99930fc41474db226bc80774b38df | null | 2008-01-01T00:04:00 | true | [OH:1][C:2]1([C:15]([OH:17])=[O:16])[C:14]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C:8]2[C:3]1=[CH:4][CH:5]=[CH:6][CH:7]=2.[CH2:18](O)[CH2:19][CH2:20][CH3:21].S(=O)(=O)(O)O.C(=O)(O)[O-].[Na+]>O.C1(C)C=CC=CC=1>[OH:1][C:2]1([C:15]([O:17][CH2:18][CH2:19][CH2:20][CH3:21])=[O:16])[C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:8]=2[C:9]2[C:14]1=[CH:13][CH:12]=[CH:11][CH:10]=2 | CCCCO | O=C(O)C1(O)c2ccccc2-c2ccccc21 | null | O=C([O-])O | O=S(=O)(O)O | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | Cc1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | To a reactor were added 0.05 mol of 9-hydroxyfluorene-9-carboxlic acid, 0.075 mol of butanol, 40 ml of toluene and 0.4 ml of concentrated sulfuric acid. The reaction was heated to reflux for 6 hrs, while water was separated by a water segregator. At the end of the reaction, the reaction mixture was neutralized with sodium bicarbonate, washed with saturated saline, extracted with ethyl acetate, and dried over anhydrous sodium sulfate. Removing the solvent gave the product with a yield of 80%. | CCCCOC(=O)C1(O)c2ccccc2-c2ccccc21 | null | 80 | null |
1,626,539 | ord_dataset-f0794d5ded7a4d3fab45cc3d7a89ee3d | null | 2015-01-01T00:09:00 | true | [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12](=[O:14])[CH3:13])=[C:5]2Cl.[CH3:16][N:17]([CH3:25])[CH2:18][CH:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1>>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12](=[O:14])[CH3:13])=[C:5]2[N:22]1[CH2:23][CH2:24][CH:19]([CH2:18][N:17]([CH3:25])[CH3:16])[CH2:20][CH2:21]1 | CN(C)CC1CCNCC1 | CC(=O)c1cnc2ccc(Br)cc2c1Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Following general procedure B, 1-(6-bromo-4-chloroquinolin-3-yl)ethanone (160 mg, 0.560 mmol) was reacted with N,N-dimethyl-1-(piperidin-4-yl)methanamine (172 mg, 0.800 mmol) to afford the desired product (17.7 mg, 8%) as an off-white solid: ESI MS m/z 390 [C19H24BrN3O+H]+. | CC(=O)c1cnc2ccc(Br)cc2c1N1CCC(CN(C)C)CC1 | null | 8.1 | null |
790,856 | ord_dataset-530502f8e61e455784f93c5faa45c94b | null | 2007-01-01T00:09:00 | true | [C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@@H:10]([N:13]2[CH2:19][C:18]3[CH:20]=[CH:21][C:22]([Cl:24])=[CH:23][C:17]=3[NH:16][C:15](=[O:25])[CH2:14]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH2:28](I)[CH3:29]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@@H:10]([N:13]2[CH2:19][C:18]3[CH:20]=[CH:21][C:22]([Cl:24])=[CH:23][C:17]=3[N:16]([CH2:28][CH3:29])[C:15](=[O:25])[CH2:14]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3] | CCI | CC(C)(C)OC(=O)N1CC[C@@H](N2CC(=O)Nc3cc(Cl)ccc3C2)C1 | null | [H-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | 0 | 0.25 | (R)-3-(8-Chloro-2-oxo-1,2,3,5-tetrahydro-benzo[e][1,4]diazepin-4-yl)pyrrolidine-1-carboxylic acid tert-butyl ester (0.258 g, 0.70 mmol) was dissolved in THF (7 mL) and cooled to 0° C. To the solution was added NaH (0.042 g, 1.0 mmol) and stirred for 15 min, followed by ethyl iodide (0.085 mL, 1.0 mmol). The solution was allowed to warm to room temperature slowly and stir at room temperature for 14 h. The reaction was quenched with water and extracted with EtOAc (3×). The organics were collected together dried over Mg2SO4, filtered and evaporated in vacuo, then purified by Biotage flash chromatography (75% ethyl acetate/25% ethyl acetate to 100% ethyl acetate) to yield the title compound (0.130 g, 47%). 1H-NMR (CDCl3): δ 1.16 (t, 3H), 1.43 (s, 9H), 1.75 (sextet, 1H), 2.18 (pentet, 1H), 3.05–3.9 (m, 1H), 7.20 (m, 3H). ESI-MS m/z: 394 (M+1), retention time 2.25. | CCN1C(=O)CN([C@@H]2CCN(C(=O)OC(C)(C)C)C2)Cc2ccc(Cl)cc21 | null | 47.1 | null |
1,431,187 | ord_dataset-5e6956e6e8c24a168866a253f4a66c6c | null | 2014-01-01T00:05:00 | true | [CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[CH:8][C:9]3[N:10]([N:12]=[C:13]([C:16]4[CH:33]=[CH:32][C:19]([O:20][CH2:21][C@@H:22]([NH:24][C:25](=O)[O:26]C(C)(C)C)[CH3:23])=[CH:18][C:17]=4[F:34])[C:14]=3[F:15])[CH:11]=2)[CH2:3][CH2:2]1.Cl.[C:36](OCC)(=O)C>C(OCC)(=O)C>[CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[CH:8][C:9]3[N:10]([N:12]=[C:13]([C:16]4[CH:33]=[CH:32][C:19]([O:20][CH2:21][C@@H:22]([NH:24][C:25](=[O:26])[CH3:36])[CH3:23])=[CH:18][C:17]=4[F:34])[C:14]=3[F:15])[CH:11]=2)[CH2:3][CH2:2]1 | CCOC(C)=O | C[C@@H](COc1ccc(-c2nn3cc(OCC4CC4)ccc3c2F)c(F)c1)NC(=O)OC(C)(C)C | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | 25 | 6 | A mixture of tert-butyl [(1S)-2-{4-[6-(cyclopropylmethoxy)-3-fluoropyrazolo[1,5-a]pyridin-2-yl]-3-fluorophenoxy}-1-methylethyl]carbamate (67 mg), 4 M hydrogen chloride/ethyl acetate (2 mL), and ethyl acetate (1 mL) was stirred at room temperature for 6 hr. The mixture was concentrated under reduced pressure. The residue was mixed with pyridine (1 mL) and acetic anhydride (1 mL). The mixture was stirred at room temperature overnight. 1 M hydrochloric acid was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (33.4 mg) as white crystals. | CC(=O)N[C@@H](C)COc1ccc(-c2nn3cc(OCC4CC4)ccc3c2F)c(F)c1 | null | null | null |
1,627,402 | ord_dataset-f0794d5ded7a4d3fab45cc3d7a89ee3d | null | 2015-01-01T00:09:00 | true | CC(C)([O-])C.[K+].[Br:7][C:8]1[CH:13]=[CH:12][NH:11][C:10](=[O:14])[CH:9]=1.C(=O)([O-])[O-].[K+].[K+].CC1C=CC(S(O[CH:32]2[CH2:37][CH2:36][N:35]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:34][CH2:33]2)(=O)=O)=CC=1>COCCOC>[Br:7][C:8]1[CH:13]=[CH:12][N:11]([CH:32]2[CH2:37][CH2:36][N:35]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:34][CH2:33]2)[C:10](=[O:14])[CH:9]=1 | O=c1cc(Br)cc[nH]1 | Cc1ccc(S(=O)(=O)OC2CCN(C(=O)OC(C)(C)C)CC2)cc1 | null | CC(C)(C)[O-] | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | COCCOC | null | null | null | null | null | null | null | null | null | null | 25 | 0.17 | Potassium tert-butoxide (7.09 g) was added at room temperature to a mixture of 4-bromopyridin-2(1H)-one (10 g) in DME (287 mL). The reaction mixture was stirred at room temperature for 10 minutes. Then, potassium carbonate (15.9 g) and tert-butyl 4-(((4-methylphenyl)sulfonyl)oxy)piperidine-1-carboxylate (37.8 g) were added thereto, and the mixture was stirred at 85 C for 1 day, at 95 C for 1 day, and at 100 C for 1 day in a nitrogen atmosphere. Saturated saline was added to the reaction mixture, followed by extraction with ethyl acetate twice. The obtained organic layer was washed with saturated saline and dried over anhydrous magnesium sulfate, and then, the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (14.7 g). | CC(C)(C)OC(=O)N1CCC(n2ccc(Br)cc2=O)CC1 | null | 71.6 | null |
1,286,852 | ord_dataset-d5c54236ecd94d61aaa071461bcfc426 | null | 2013-01-01T00:04:00 | true | C([N:8](CC1C=CC=CC=1)[CH:9]1[CH2:13][CH:12]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH:11]([CH2:19][CH3:20])[CH2:10]1)C1C=CC=CC=1.[H][H]>CCO.[OH-].[OH-].[Pd+2]>[NH2:8][CH:9]1[CH2:13][CH:12]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH:11]([CH2:19][CH3:20])[CH2:10]1 | CCOC(=O)C1CC(N(Cc2ccccc2)Cc2ccccc2)CC1CC | [H][H] | null | [Pd+2] | [OH-] | 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 | To a vessel containing a slurry of 20 wt % Pd(OH)2 on C (12.9 g, 18.4 mmol) in EtOH (1.0 L) was added ethyl 4-(dibenzylamino)-2-ethylcyclopentanecarboxylate (129 g, 352 mmol). The reaction was shaken for about 90 min at about 50° C. under about 30 psi of hydrogen. After removal of the hydrogen source, a nitrogen atmosphere was introduced and the resulting mixture was filtered through a pad of Celite® and the filtrate was coned under reduced pressure to give ethyl 4-amino-2-ethylcyclopentanecarboxylate (64.5 g, 99%) as a yellow syrup: 1H NMR (CDCl3) δ 4.03-3.88 (m, 2H), 3.17 (m, 1H), 2.68 (m, 1H), 2.09-2.02 (m, 2H), 2.02-1.94 (m, 2H), 1.84 (m, 1H), 1.58-1.48 (m, 1H), 1.32-1.18 (m, 1H), 1.09 (m, 3H), 1.03 (m, 2H), 0.78-0.69 (m, 3H). | CCOC(=O)C1CC(N)CC1CC | null | 98.9 | null |
1,532,380 | ord_dataset-8d5c200bca27407ab9febe7598e16458 | null | 2015-01-01T00:01:00 | true | [F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[N:8]=[C:7]2O.O=P(Cl)(Cl)[Cl:20]>>[Cl:20][C:7]1[C:6]2[C:11](=[C:2]([F:1])[CH:3]=[CH:4][CH:5]=2)[N:10]=[C:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[N:8]=1 | CCOC(=O)c1nc(O)c2cccc(F)c2n1 | O=P(Cl)(Cl)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 | null | null | A mixture of ethyl 8-fluoro-4-hydroxyquinazoline-2-carboxylate (530 mg, 2.2 mmol) and POCl3 (3 mL) was heated under reflux for 5 h. The mixture was concentrated under reduced pressure, and then toluene was twice added and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 0-25% EtOAc/hexanes to afford ethyl 4-chloro-8-fluoroquinazoline-2-carboxylate (365 mg, 65%). 1H NMR (300 MHz, DMSO-d6) δ 1.39 (t, J=7.1 Hz, 3H), 4.46 (q, J=7.1 Hz, 2H), 7.97-8.06 (m, 1H), 8.07-8.16 (m, 1H), 8.18-8.24 (m, 1H). | CCOC(=O)c1nc(Cl)c2cccc(F)c2n1 | null | 65 | null |
264,915 | ord_dataset-a7bd0db0684c464bb02ff6a36065fee3 | null | 1993-01-01T00:03:00 | true | Cl.[F:2][C:3]1[CH:16]=[CH:15][C:6]([C:7]([CH:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[O:8])=[CH:5][CH:4]=1.[C:17]1([S:23](Cl)(=[O:25])=[O:24])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>N1C=CC=CC=1>[F:2][C:3]1[CH:4]=[CH:5][C:6]([C:7]([CH:9]2[CH2:14][CH2:13][N:12]([S:23]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)(=[O:25])=[O:24])[CH2:11][CH2:10]2)=[O:8])=[CH:15][CH:16]=1 | O=S(=O)(Cl)c1ccccc1 | O=C(c1ccc(F)cc1)C1CCNCC1 | 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 | 25 | 8 | A mixture of 4-(4-fluorobenzoyl)piperidine hydrochloride (53.30 g, 0.219 mol) and benzenesulfonyl chloride (44 g, 0.25 mol) in 500 mL of pyridine was stirred at room temperature overnight. The solvent was removed in vacuo, and the residue was partitioned between CH2Cl2 and dilute NaOH. The CH2Cl2 solution was extracted with dilute H2SO4 and then dried (MgSO4). The volume was reduced to 400 mL, hexane was added, and 39.20 g (50.6%) of the title compound was collected as a white crystalline solid, mp 156.5°-158° C. | O=C(c1ccc(F)cc1)C1CCN(S(=O)(=O)c2ccccc2)CC1 | null | null | null |
988,780 | ord_dataset-35b56288528641309a040cc2b6710b61 | null | 2010-01-01T00:08:00 | true | [S:1]1[C:5]([CH2:6][O:7][C:8]([NH:10][C@H:11]([CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH2:12][NH:13][CH2:14][C@H:15]([NH:23][C:24]([O:26][CH2:27][C:28]2[S:32][CH:31]=[N:30][CH:29]=2)=[O:25])[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:9])=[CH:4][N:3]=[CH:2]1.[CH:40](=O)[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>>[CH2:40]([N:13]([CH2:14][C@H:15]([NH:23][C:24]([O:26][CH2:27][C:28]1[S:32][CH:31]=[N:30][CH:29]=1)=[O:25])[CH2:16][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)[CH2:12][C@H:11]([NH:10][C:8]([O:7][CH2:6][C:5]1[S:1][CH:2]=[N:3][CH:4]=1)=[O:9])[CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1 | O=C(N[C@@H](CNC[C@@H](Cc1ccccc1)NC(=O)OCc1cncs1)Cc1ccccc1)OCc1cncs1 | O=Cc1ccccc1 | null | CC(=O)O[BH-](OC(C)=O)OC(C)=O | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(=O)O | null | null | null | null | null | null | null | null | null | null | null | null | The product from Example 31D (80 mg, 0.141 mmol), benzaldehyde (17 μl, 0.170 mmol), acetic acid (10 μl, 0.166 mmol), and sodium triacetoxyborohydride (48 mg, 0.226 mmol) were processed as described in Example 27 to provide the title compound (17 mg, 18%). 1H NMR (CDCl3) δ 8.73 (s, 2H), 7.78 (s, 2H), 7.32-7.08 (m, 15H), 5.12 (br s, 2H), 4.84 (brs, 2H), 4.12 (s, 2H), 3.13 (dd, 2H), 3.05-2.87 (m, 6H), 2.80-2.70 (m, 2H); MS (ESI+) m/z 656 (M+H)+. | O=C(N[C@H](Cc1ccccc1)CN(Cc1ccccc1)C[C@@H](Cc1ccccc1)NC(=O)OCc1cncs1)OCc1cncs1 | null | 18.4 | null |
906,470 | ord_dataset-46d216f2c4374ef5b9df90427e2a4cd4 | null | 2009-01-01T00:09:00 | true | [Na].[Cl-].[NH2:3][C:4]([NH2:6])=[NH2+:5].[F:7][C:8]([F:30])([F:29])[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[CH:14]([CH2:18][C:19](OCC)=[O:20])[N:13]([CH2:24][CH:25]([CH3:27])[CH3:26])[C:12]2=[O:28]>C(O)C.C(OCC)C>[F:30][C:8]([F:7])([F:29])[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[CH:14]([CH2:18][C:19]([NH:5][C:4]([NH2:6])=[NH:3])=[O:20])[N:13]([CH2:24][CH:25]([CH3:27])[CH3:26])[C:12]2=[O:28] | NC(N)=[NH2+] | CCOC(=O)CC1c2ccc(C(F)(F)F)cc2C(=O)N1CC(C)C | null | [Cl-] | [Na] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOCC | CCO | null | null | null | null | null | null | null | null | null | 20 | 16 | N-[2-(2-Isobutyl-3-oxo-5-trifluoromethyl-2,3-dihydro-1H-isoindol-1-yl)-acetyl]-guanidine is prepared as described in Example 9, starting with 10 cm3 of absolute ethanol, 0.19 g of sodium, 0.78 g of guanidinium chloride and 1.86 g of ethyl (5-trifluoromethyl-2-isobutyl-3-oxo-2,3-dihyrdo-1H-isoindol-1-yl)acetate in 10 cm3 of absolute ethanol. The reaction mixture is stirred at a temperature in the region of 20° C. for 16 hours and is then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The residue is then taken up in a mixture of 5 cm3 of water and 15 cm3 of diethyl ether and then concentrated to dryness again under the same conditions. The residue is taken up in 100 cm3 of ethyl acetate and the organic phase is washed with twice 60 cm3 of aqueous 1N sodium hydroxide solution and then with twice 60 cm3 of 4N hydrochloric acid solution. The acidic aqueous extracts are combined, treated with aqueous 30% sodium hydroxide solution to pH 14, and then extracted with 3 times 50 cm3 of ethyl acetate. The organic extracts are combined, washed with 100 cm3 of saturated sodium chloride solution, dried over magnesium sulfate and concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The yellow solid thus obtained is taken up in 20 cm3 of diethyl ether, stirred at a temperature in the region of 20° C. for 1 hour and then filtered off. The solid is washed with twice 20 cm3 of diethyl ether and then dried in a desiccator under reduced pressure (2 Pa) at a temperature in the region of 35° C. 0.34 g of N-[(5-trifluoromethyl-2-isobutyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)acetyl]guanidine is thus obtained in the form of a yellow powder melting at 224° C. (Analysis: C16 H19 F3 N4 O2% calculated C, 53.93; H, 5.37; F, 15.99; N, 15.72; O, 8.98%. found C, 53.95; H, 5.15; F, 15.00; N, 15.59). | CC(C)CN1C(=O)c2cc(C(F)(F)F)ccc2C1CC(=O)NC(=N)N | null | 17.6 | null |
1,445,446 | ord_dataset-a86112d52cd54525a5e36d41f18aced2 | null | 2014-01-01T00:07:00 | true | N1CCCCC1.[NH:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9][C:8]1=[O:16].[N:17]1[CH:22]=[CH:21][C:20](/[CH:23]=[CH:24]/[C:25]2[C:33]3[C:28](=[CH:29][CH:30]=[C:31]([CH:34]=O)[CH:32]=3)[N:27]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:42])[CH3:41])[N:26]=2)=[CH:19][CH:18]=1>CCO>[N:17]1[CH:22]=[CH:21][C:20](/[CH:23]=[CH:24]/[C:25]2[C:33]3[C:28](=[CH:29][CH:30]=[C:31]([CH:34]=[C:9]4[C:10]5[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=5)[NH:7][C:8]4=[O:16])[CH:32]=3)[N:27]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:42])[CH3:41])[N:26]=2)=[CH:19][CH:18]=1 | O=C1Cc2ccccc2N1 | C[Si](C)(C)CCOCn1nc(/C=C/c2ccncc2)c2cc(C=O)ccc21 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | C1CCNCC1 | null | null | null | null | null | null | null | null | null | 75 | null | A solution of piperidine (0.2M in EtOH, 0.10 mL, 0.02 mmol) was added to a suspension of oxindole (16.5 mg, 0.12 mmol) and (E)-3-(2-(pyridin-4-yl)vinyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-5-carbaldehyde (42.5 mg, 0.11 mmol) in EtOH (4 mL). The reaction was then heated to 75° C. for 15 hrs. The solvent was evaporated in vacuo. MeOH was added and the resulting suspension was sonicated, but the solution was still cloudy even after EtOAc was added. The solid was removed by filtration and the solvent evaporated in vacuo. Chromatography (5 g silica SPE tube, Silicycle, 2% MeOH in CH2Cl2) gave a yellow solid (35 mg, 64%, 55:45 mixture of E/Z isomers). 1H NMR (400 MHz, CDCl3 plus a drop of CD3OD) δ 9.77 (s, 0.45H), 8.63 (m, 1.9H), 8.42 (s, 0.55H), 8.18 (s, 0.45H), 8.14 (dd, J=8.8, 1.2 Hz, 0.45H), 8.00 (s, 1H), 7.83-7.42 (m, 7H), 7.26 (t, J=7.6 Hz, 1H), 7.09 (t, J=7.6 Hz, 0.45H), 6.94-6.88 (m, 1.6H), 5.80 (s, 0.55H), 5.77 (s, 0.45H), 3.64 (m, 2H), 0.95 (m, 2H), −0.02 (s, 5H), −0.03 (s, 4H). | C[Si](C)(C)CCOCn1nc(/C=C/c2ccncc2)c2cc(C=C3C(=O)Nc4ccccc43)ccc21 | null | null | null |
866,407 | ord_dataset-b8b98725045d45bdbd73512048f4b47e | null | 2009-01-01T00:02:00 | true | [H-].[H-].[H-].[H-].[Li+].[Al+3].[Cl:7][C:8]1[CH:13]=[C:12]2[NH:14][C:15](=[O:47])[C:16]3([CH:21]([C:22]4[CH:27]=[C:26]([Cl:28])[CH:25]=[CH:24][C:23]=4[O:29][C:30]4([C:34](OC)=[O:35])[CH2:33][CH2:32][CH2:31]4)[CH2:20][C:19](=[O:38])[NH:18][CH:17]3[C:39]3[CH:44]=[C:43]([F:45])[CH:42]=[CH:41][C:40]=3[CH3:46])[C:11]2=[CH:10][CH:9]=1>C1COCC1>[Cl:7][C:8]1[CH:13]=[C:12]2[NH:14][C:15](=[O:47])[C:16]3([CH:21]([C:22]4[CH:27]=[C:26]([Cl:28])[CH:25]=[CH:24][C:23]=4[O:29][C:30]4([CH2:34][OH:35])[CH2:33][CH2:32][CH2:31]4)[CH2:20][C:19](=[O:38])[NH:18][CH:17]3[C:39]3[CH:44]=[C:43]([F:45])[CH:42]=[CH:41][C:40]=3[CH3:46])[C:11]2=[CH:10][CH:9]=1 | COC(=O)C1(Oc2ccc(Cl)cc2C2CC(=O)NC(c3cc(F)ccc3C)C23C(=O)Nc2cc(Cl)ccc23)CCC1 | null | null | [Al+3] | [H-] | [Li+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | null | 1.5 | To a mixture of LiAlH4 (15 mg, 0.4 mmol) in THF (2 mL) was added racemic (2′S,3S,4′R)-6-chloro-4′-[5-chloro-2-(1-methoxycarbonyl-cyclobutoxy)-phenyl]-2′-(5-fluoro-2-methyl-phenyl)spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione (RO5247453-000) (60 mg, 0.1 mmol). The mixture was stirred in a ice bath for 1.5 h, quenched with MeOH, purified by Prep-HPLC to give title compound (14 mg, 24%). m/z (M+H)+: 569 | Cc1ccc(F)cc1C1NC(=O)CC(c2cc(Cl)ccc2OC2(CO)CCC2)C12C(=O)Nc1cc(Cl)ccc12 | null | 24.6 | null |
1,018,115 | ord_dataset-f024e9664ab64906a71a2ff6004cb3d0 | null | 2010-01-01T00:12:00 | true | [NH2:1][C:2]1[CH:27]=[CH:26][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]([N:16]3[CH2:21][CH2:20][CH:19]([CH2:22][N:23]([CH3:25])[CH3:24])[CH2:18][CH2:17]3)=[O:15])[CH:8]=2)=[C:4]([F:28])[CH:3]=1.[F:29][C:30]1[CH:35]=[CH:34][C:33]([NH:36][C:37]([C:39]2([C:43](O)=[O:44])[CH2:42][CH2:41][CH2:40]2)=[O:38])=[CH:32][CH:31]=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>CN(C)C=O>[CH3:24][N:23]([CH2:22][CH:19]1[CH2:18][CH2:17][N:16]([C:14]([NH:13][C:9]2[CH:8]=[C:7]([O:6][C:5]3[CH:26]=[CH:27][C:2]([NH:1][C:43]([C:39]4([C:37]([NH:36][C:33]5[CH:34]=[CH:35][C:30]([F:29])=[CH:31][CH:32]=5)=[O:38])[CH2:42][CH2:41][CH2:40]4)=[O:44])=[CH:3][C:4]=3[F:28])[CH:12]=[CH:11][N:10]=2)=[O:15])[CH2:21][CH2:20]1)[CH3:25] | CN(C)CC1CCN(C(=O)Nc2cc(Oc3ccc(N)cc3F)ccn2)CC1 | O=C(O)C1(C(=O)Nc2ccc(F)cc2)CCC1 | 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 | CN(C)C=O | CCN(CC)CC | null | null | null | null | null | null | null | null | null | null | 8 | 4-(Dimethylaminomethyl)piperidine-1-carboxylic acid [4-(4-amino-2-fluorophenoxy)pyridin-2-yl]amide (114 mg) was dissolved in N,N-dimethylformamide (4.0 ml). 1-(4-Fluorophenylcarbamoyl)cyclobutanecarboxylic acid (279 mg), triethylamine (0.164 ml) and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (520 mg) were added under a nitrogen atmosphere at room temperature and stirred overnight. Liquid-liquid separation was carried out after addition of ethyl acetate and water to the reaction mixture. The organic layer was washed with 0.5N hydrochloric acid (4 times), water, a saturated aqueous solution of sodium hydrogencarbonate (3 times) and brine in this order, and dried over anhydrous sodium sulfate. The solvent was removed and the resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate, then ethyl acetate:methanol=98:2). Fractions containing the target compound were concentrated under reduced pressure. A solid was precipitated by addition of a mixture of diethyl ether and heptane (1:3) to the resultant residue. The solid was collected by filtration and dried under aeration to provide the titled compound as white powder (19.1 mg, 11%). | CN(C)CC1CCN(C(=O)Nc2cc(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CCC4)cc3F)ccn2)CC1 | null | 10.7 | null |
708,690 | ord_dataset-c8069773c1a148aca8ab417108daacc5 | null | 2006-01-01T00:05:00 | true | I[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[OH:10].[CH:11]#[C:12][CH2:13][CH3:14]>>[CH3:9][O:8][C:5]1[CH:6]=[CH:7][C:2]2[CH:11]=[C:12]([CH2:13][CH3:14])[O:10][C:3]=2[CH:4]=1 | C#CCC | COc1ccc(I)c(O)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | This material was prepared from 2-iodo-5-methoxyphenol (1 g, 4 mmole) and 1-butyne in a manner as previously described for example 12a to give 570 mg (81%) of a brown oil. 1H NMR (CDCl3) δ 7.33 (1H, d, J=8.6 Hz), 6.97 (1H, d, J=2.2 Hz), 6.80 (1H, dd, J=2.2, 8.6 Hz), 6.26 (1H, s), 3.83 (3H, s), 3.04 (2H, q, J=7.3 Hz), 1.28 (3H, t, J=7.3 Hz). | CCc1cc2ccc(OC)cc2o1 | null | 81 | null |
596,866 | ord_dataset-843ef38b45484f72826f5f39d8a29c4d | null | 2003-01-01T00:06:00 | true | [N+](C1C=CC(COC([NH:12][CH2:13][CH2:14][CH2:15][O:16][C:17]2[CH:18]=[CH:19][C:20]3[CH2:26][CH:25]([CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])[C:24]4[CH:33]=[CH:34][CH:35]=[CH:36][C:23]=4[CH2:22][C:21]=3[CH:37]=2)=O)=CC=1)([O-])=O>[Pd].C(O)C>[NH2:12][CH2:13][CH2:14][CH2:15][O:16][C:17]1[CH:18]=[CH:19][C:20]2[CH2:26][CH:25]([CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])[C:24]3[CH:33]=[CH:34][CH:35]=[CH:36][C:23]=3[CH2:22][C:21]=2[CH:37]=1 | CCOC(=O)CC1Cc2ccc(OCCCNC(=O)OCc3ccc([N+](=O)[O-])cc3)cc2Cc2ccccc21 | 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 | null | 3 | A mixture of ethyl (±)-10,11-dihydro-3-[3-(4-nitrobenzyloxycarbonylamino)-1-propyloxy]-5H-dibenzo[a,d]cycloheptene-10-acetate (1.6 g 3 mmol), 10% palladium on charcoal (0.8 g, 1 mmol), and ethanol (50 mL) was shaken under H2 (48 psi) for 3 hr, then the catalyst was removed by filtration through celite®D. The filtrate was concentrated to give the title compound (1.2 g, 100%) as a yellow oil: MS (ES) 348.2 (M+H)+. | CCOC(=O)CC1Cc2ccc(OCCCN)cc2Cc2ccccc21 | null | 113.2 | null |
1,075,138 | ord_dataset-afd812677c134591a99f46ce28de2524 | null | 2011-01-01T00:08:00 | true | [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[N:12]=[C:13]=[O:14].[NH2:15][C:16]1[CH:17]=[C:18]([CH:30]=[CH:31][CH:32]=1)[CH2:19][CH2:20][NH:21][C:22]1[C:23]([C:27]([NH2:29])=[O:28])=[N:24][NH:25][CH:26]=1>C1COCC1.C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[NH:12][C:13](=[O:14])[NH:15][C:16]1[CH:17]=[C:18]([CH:30]=[CH:31][CH:32]=1)[CH2:19][CH2:20][NH:21][C:22]1[C:23]([C:27]([NH2:29])=[O:28])=[N:24][NH:25][CH:26]=1 | O=C=Nc1cc(C(F)(F)F)ccc1F | NC(=O)c1n[nH]cc1NCCc1cccc(N)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOC(C)=O | C1CCOC1 | null | null | null | null | null | null | null | null | null | 20 | 12 | A solution of 0.14 ml of 1-fluoro-2-isocyanato-4-trifluoromethylbenzene is added at 20° C. to a solution of 0.25 g of 4-[(3-aminobenzyl)methylamino]-1H-pyrazole-3-carboxamide in 25 ml of anhydrous THF. The reaction medium is stirred for 12 hours at 20° C. and then diluted with 100 ml of ethyl acetate. The organic phase is washed with 50 ml of distilled water, and is then separated out by settling of the phases, dried over magnesium sulfate and evaporated to dryness under reduced pressure. The residue obtained is chromatographed on a column of silica (15 g of Merck cartridge silica with a particle size of 15 to 45 μm, column diameter 2.2 cm, 5 ml fractions, flow rate of 10 ml/min, eluent 95/5 dichloromethane/methanol—by volume). Fractions 35 to 95 are combined and evaporated to dryness under reduced pressure. 0.02 g of 4-({3-[3-(2-fluoro-5-trifluoromethylphenyl)ureido]benzyl}methylamino)-1H-pyrazole-3-carboxamide is obtained in the form of a solid. ([M+H]+): 451). RT: 3.55 min (Method A). | NC(=O)c1n[nH]cc1NCCc1cccc(NC(=O)Nc2cc(C(F)(F)F)ccc2F)c1 | null | null | null |
922,128 | 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.[F:16][C:17]1[CH:24]=[CH:23][CH:22]=[CH:21][C:18]=1[CH2:19]Br>CN(C)C=O>[F:16][C:17]1[CH:24]=[CH:23][CH:22]=[CH:21][C:18]=1[CH2:19][N:3]1[C:4](=[O:15])[C:5]2[C@@H:6]3[C:11]([CH3:12])([CH3:13])[C@@:9]([CH3:14])([CH2:8][CH2:7]3)[C:10]=2[N:2]1[CH3:1] | Fc1ccccc1CBr | Cn1[nH]c(=O)c2c1[C@]1(C)CC[C@H]2C1(C)C | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | 100 | 120 | 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, 0.49 mmol) and 2-fluoro-benzyl bromide (58 μL, 0.48 mmol) in N,N-dimethylformamide (5 mL) was heated at 100° C. overnight and then allowed to stand at room temperature for five days. The reaction mixture was evaporated and the residue was purified using a Biotage 40S system, eluting with 0-1% methanol/chloroform, followed by drying under high vacuum to give (4S,7R)-2-(2-fluoro-benzyl)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (63 mg, 42%) as a white solid. APCI-MS (M+H) 315. | Cn1c2c(c(=O)n1Cc1ccccc1F)[C@H]1CC[C@]2(C)C1(C)C | null | 41.7 | null |
700,899 | ord_dataset-bbd7e53f000345838ad4920a07a169ff | null | 2006-01-01T00:03:00 | true | [F:1][C:2]([F:19])([F:18])[C:3]1[CH:4]=[C:5]([N:9]2[C:13]([CH3:14])=[C:12]([C:15]([OH:17])=O)[CH:11]=[N:10]2)[CH:6]=[CH:7][CH:8]=1.[NH2:20][C:21]1[CH:22]=[CH:23][C:24]([N:29]2[CH2:34][CH2:33][CH:32]([N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)[CH2:31][CH2:30]2)=[C:25]([CH:28]=1)[C:26]#[N:27]>>[C:26]([C:25]1[CH:28]=[C:21]([NH:20][C:15]([C:12]2[CH:11]=[N:10][N:9]([C:5]3[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:1])([F:19])[F:18])[CH:4]=3)[C:13]=2[CH3:14])=[O:17])[CH:22]=[CH:23][C:24]=1[N:29]1[CH2:34][CH2:33][CH:32]([N:35]2[CH2:36][CH2:37][O:38][CH2:39][CH2:40]2)[CH2:31][CH2:30]1)#[N:27] | Cc1c(C(=O)O)cnn1-c1cccc(C(F)(F)F)c1 | N#Cc1cc(N)ccc1N1CCC(N2CCOCC2)CC1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | By the reaction and treatment in the same manner as in Example 64 using 1-(3-trifluoromethylphenyl)-5-methylpyrazole-4-carboxylic acid (2.0 g) and 5-amino-2-(4-morpholinopiperidin-1-yl)benzonitrile (2.4 g), the title compound (1.0 g) was obtained, melting point: 215–216° C. | Cc1c(C(=O)Nc2ccc(N3CCC(N4CCOCC4)CC3)c(C#N)c2)cnn1-c1cccc(C(F)(F)F)c1 | null | 25.1 | null |
934,280 | ord_dataset-d8a5dc784dde4465894ec7c69d2e3ba6 | null | 2010-01-01T00:01:00 | true | C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:21]([NH:23][C:24]3[N:25]([C:33]4[CH:38]=[CH:37][C:36]([CH3:39])=[CH:35][CH:34]=4)[N:26]=[C:27]([C:29]([CH3:32])([CH3:31])[CH3:30])[CH:28]=3)=[O:22])=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.Cl.O1CCOCC1>C1COCC1>[C:29]([C:27]1[CH:28]=[C:24]([NH:23][C:21]([NH:20][C:17]2[CH:16]=[N:15][C:14]([N:11]3[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]3)=[CH:19][CH:18]=2)=[O:22])[N:25]([C:33]2[CH:38]=[CH:37][C:36]([CH3:39])=[CH:35][CH:34]=2)[N:26]=1)([CH3:32])([CH3:30])[CH3:31] | Cc1ccc(-n2nc(C(C)(C)C)cc2NC(=O)Nc2ccc(N3CCN(C(=O)OC(C)(C)C)CC3)nc2)cc1 | null | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | C1COCCO1 | null | null | null | null | null | null | null | null | null | 60 | null | Place 4-{5-[3-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-ureido]-pyridin-2-yl}-piperazine-1-carboxylic acid tert-butyl ester (565 mg, 1.06 mmol) in THF (10 mL). Add 4 M HCl in dioxane (2.65 mL, 10.6 mmol) and heat to 60° C. for 3 hours. Cool the reaction to room temperature and load onto a Varian™ SCX column. Wash the column with MeOH and then flush off the product with 2 M NH3 in MeOH. | Cc1ccc(-n2nc(C(C)(C)C)cc2NC(=O)Nc2ccc(N3CCNCC3)nc2)cc1 | null | null | null |
1,207,096 | ord_dataset-fb72428f30234761b4216139dc228d0c | null | 2012-01-01T00:09:00 | true | Cl.[Br:2][C:3]1[CH:4]=[C:5]([S:9](Cl)(=[O:11])=[O:10])[CH:6]=[N:7][CH:8]=1.C(N(CC)CC)C.[OH:20][CH2:21][CH2:22][NH2:23]>C(Cl)Cl>[Br:2][C:3]1[CH:4]=[C:5]([S:9]([NH:23][CH2:22][CH2:21][OH:20])(=[O:11])=[O:10])[CH:6]=[N:7][CH:8]=1 | O=S(=O)(Cl)c1cncc(Br)c1 | NCCO | null | Cl | 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 | A cooled (0° C.) solution of 5-bromopyridine-3-sulfonyl chloride hydrochloride (3.00 g, 10.2 mmol) in DCM (50 ml) was slowly treated with triethylamine (4.3 ml) and stirred until a clear solution was obtained. This solution was treated dropwise with 2-hydroxyethylamine (0.68 g, 0.68 mL) and stirred at RT for 16 hours. The reaction mixture was washed successively with water and brine, the organic layer was dried with sodium sulfate and evaporated under reduced pressure. The crude product was purified by column chromatography (silica) eluting with 20% ethyl acetate in petroleum ether, to give the title compound. | O=S(=O)(NCCO)c1cncc(Br)c1 | null | null | null |
1,034,252 | ord_dataset-83acb82dc5ba4f7aba439b9875aaac43 | null | 2011-01-01T00:02:00 | true | [CH3:1][O:2][C:3]([C:5]1[C:13]2[N:12]=[C:11]([NH2:14])[NH:10][C:9]=2[CH:8]=[CH:7][CH:6]=1)=[O:4].COC(=O)C1C=C([C:24]2[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=2)C=C([N+]([O-])=O)C=1N>>[CH3:1][O:2][C:3]([C:5]1[C:13]2[N:12]=[C:11]([NH2:14])[NH:10][C:9]=2[CH:8]=[C:7]([C:24]2[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=2)[CH:6]=1)=[O:4] | COC(=O)c1cccc2[nH]c(N)nc12 | COC(=O)c1cc(-c2ccncc2)cc([N+](=O)[O-])c1N | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | 0.25 g (50% overall yield) of 2-amino-6-pyridin-4-yl-1H-benzoimidazole-4-carboxylic acid methyl ester was synthesized according to procedures described for the synthesis of 2-Amino-1H-benzoimidazole-4-carboxylic acid methyl ester (intermediate A) starting from 0.5 g (1.8 mmol) of above synthesized 2-Amino-3-nitro-5-pyridin-4-yl-benzoic acid methyl ester. LCMS: 269 (M+1)+. | COC(=O)c1cc(-c2ccncc2)cc2[nH]c(N)nc12 | null | 50 | null |
1,331,645 | ord_dataset-cfad8b3f00044bcda60a96b019f09872 | null | 2013-01-01T00:08:00 | true | C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[F:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[N:23]=[CH:24][N:25]([CH:35]3[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]3)[C:26]=2[C:27]2[CH:32]=[CH:31][N:30]=[C:29]([NH:33][CH3:34])[N:28]=2)=[CH:18][CH:17]=1.[O:41]1[CH:45]=[CH:44][C:43]([CH:46]=O)=[N:42]1.C(OCC)C>C1COCC1>[F:15][C:16]1[CH:17]=[CH:18][C:19]([C:22]2[N:23]=[CH:24][N:25]([CH:35]3[CH2:40][CH2:39][N:38]([CH2:46][C:43]4[CH:44]=[CH:45][O:41][N:42]=4)[CH2:37][CH2:36]3)[C:26]=2[C:27]2[CH:32]=[CH:31][N:30]=[C:29]([NH:33][CH3:34])[N:28]=2)=[CH:20][CH:21]=1 | O=Cc1ccon1 | CNc1nccc(-c2c(-c3ccc(F)cc3)ncn2C2CCNCC2)n1 | null | CC(=O)O[BH-](OC(C)=O)OC(C)=O | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOCC | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | 1.5 | Sodium triacetoxyborohydride (135 mg, 0.637 mmol) was added to a solution of 4-[4-(4-fluorophenyl)-1-piperidin-4-yl-1H-imidazol-5-yl]-N-methylpyrimidin-2-amine (C8) (150 mg, 0.426 mmol) and isoxazole-3-carbaldehyde (49.6 mg, 0.511 mmol) in THF (10 mL). After 90 minutes at room temperature, the reaction was concentrated in vacuo and partitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide a thick oil. Purification via silica gel chromatography (Eluants: ethyl acetate followed by 10% methanol in ethyl acetate) provided a viscous oil, which was reconcentrated from diethyl ether to afford the product as a white solid. Yield: 77 mg, 0.18 mmol, 42%. LCMS m/z 434.6 (M+1). 1H NMR (400 MHz, CDCl3) δ 1.99-2.09 (m, 2H), 2.16-2.22 (m, 4H), 3.03 (m, 2H), 3.05 (d, J=5.1 Hz, 3H), 3.69 (s, 2H), 4.67 (br m, 1H), 5.17 (m, 1H), 6.41 (d, J=5.1 Hz, 1H), 6.41 (d, J=1.7 Hz, 1H), 7.00 (dd, J=8.7, 8.7 Hz, 2H), 7.46 (dd, J=8.7, 5.4 Hz, 2H), 7.77 (s, 1H), 8.16 (br d, J=4.5 Hz, 1H), 8.40 (d, J=1.6 Hz, 1H). | CNc1nccc(-c2c(-c3ccc(F)cc3)ncn2C2CCN(Cc3ccon3)CC2)n1 | null | null | null |
855,028 | ord_dataset-faa0236be76c4501841c954527cd1b6c | null | 2008-01-01T00:12:00 | true | [NH2:1][C:2]1[C:11]2[C:6](=[C:7](Br)[CH:8]=[CH:9][CH:10]=2)[N:5]=[N:4][C:3]=1[C:13]([NH:15][CH2:16][CH3:17])=[O:14].[CH3:18][O:19][C:20]1[CH:25]=[CH:24][N:23]=[CH:22][C:21]=1B(O)O>>[NH2:1][C:2]1[C:11]2[C:6](=[C:7]([C:21]3[CH:22]=[N:23][CH:24]=[CH:25][C:20]=3[O:19][CH3:18])[CH:8]=[CH:9][CH:10]=2)[N:5]=[N:4][C:3]=1[C:13]([NH:15][CH2:16][CH3:17])=[O:14] | COc1ccncc1B(O)O | CCNC(=O)c1nnc2c(Br)cccc2c1N | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The title compound was prepared from 4-amino-8-bromo-N-ethyl-cinnoline-3-carboxamide (70.0 mg, 0.237 mmol) and 4-methoxy-3-pyridine boronic acid (153.0 mg, 0.3439 mmol) according to Method A except that the extraction was carried out with methylene chloride rather than ethyl acetate and the flash column was eluted with a gradient of 10to 60% methanol in dichloromethane. The concentrated product was then recrystallized from chloroform (with a few drops of methanol) and hexanes to afford the title compound as a yellow solid (19.6 mg, 26% yield). 1H NMR (300.132 MHz, CDCl3) δ 8.58 (d, J=5.7 Hz, 1H), 8.52-8.43 (bm, 1H), 8.46 (s, 1H), 7.92 (app quintet, J=4.0 Hz, 1H), 7.74 (dd, J=4.9, 0.9 Hz, 2H), 6.96 (d, J=5.8 Hz, 1H), 3.78 (s, 3H), 3.53 (dq, J=5.8, 7.3, Hz, 2H), 1.27 (t, J=7.3 Hz, 3H). MS APCI, m/z=324 (M+H). HPLC 1.42 min. | CCNC(=O)c1nnc2c(-c3cnccc3OC)cccc2c1N | null | 25.6 | null |
731,110 | ord_dataset-eb4226b4f7644a01a737e7547b70014a | null | 2006-01-01T00:09:00 | true | [O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH2:12][CH2:13][CH2:14][CH2:15][C:16]#[N:17].[N:18]([Si](C)(C)C)=[N+:19]=[N-:20].C([Sn](=O)CCCC)CCC>C1(C)C=CC=CC=1>[N:17]1[NH:18][N:19]=[N:20][C:16]=1[CH2:15][CH2:14][CH2:13][CH2:12][N:3]1[C:4](=[O:11])[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:2]1=[O:1] | N#CCCCCN1C(=O)c2ccccc2C1=O | C[Si](C)(C)N=[N+]=[N-] | null | CCCC[Sn](=O)CCCC | 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 | 100 | null | To a solution of 5-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-pentanenitrile (6.84 g, 30 mmol) and azidotrimethylsilane (14 mL, 108 mmol) in toluene (40 mL) was added dibutyltin oxide (2.1 g, 6.0 mmol). The mixture was heated at 100° C. for 48 h, concentrated, and flash chromatographed on silica gel column, eluting with EtOAc/DCM (30 and 60%) followed by methanol/DCM (2.5 and 5%) to give the title compound (6.72 g, 83% yield) as a white solid. | O=C1c2ccccc2C(=O)N1CCCCc1nn[nH]n1 | null | 82.6 | null |
896,183 | ord_dataset-de6bce51790e4004a27e1a8f2bcc7ded | null | 2009-01-01T00:08:00 | true | Cl.[CH3:2][O:3][C:4]1[CH:9]=[CH:8][C:7]([C@@H:10]2[O:15][CH2:14][CH2:13][NH:12][CH2:11]2)=[CH:6][CH:5]=1.Cl[C:17]1[N:22]([CH3:23])[C:21](=[O:24])[CH:20]=[C:19]([C:25]2[CH:30]=[CH:29][N:28]=[CH:27][N:26]=2)[N:18]=1.C(N(CC)CC)C>O1CCCC1>[CH3:2][O:3][C:4]1[CH:5]=[CH:6][C:7]([C@@H:10]2[O:15][CH2:14][CH2:13][N:12]([C:17]3[N:22]([CH3:23])[C:21](=[O:24])[CH:20]=[C:19]([C:25]4[CH:30]=[CH:29][N:28]=[CH:27][N:26]=4)[N:18]=3)[CH2:11]2)=[CH:8][CH:9]=1 | COc1ccc([C@H]2CNCCO2)cc1 | Cn1c(Cl)nc(-c2ccncn2)cc1=O | null | Cl | 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 | A solution of (S)-2-(4-methoxyphenyl)morpholine hydrochloride (0.30 g, 1.35 mmol), 2-chloro-3-methyl-6-(4-pyrimidyl)-pyrimidin-4-one (0.40 g, 1.75 mmol) and triethylamine (0.56 ml, 4.05 mmol) in tetrahydrofuran(6 ml) was refluxed for several hours. The reaction mixture was removed in vacuo. The residue was dissolved in 1N hydrochloric acid and extracted with dichloromethane. The organic phase was washed with saturated aqueous sodium hydrogen carbonate, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by column chromatography on silica gel with ethyl acetate as the eluent to give the title compound (463 mg, 90%) | COc1ccc([C@H]2CN(c3nc(-c4ccncn4)cc(=O)n3C)CCO2)cc1 | null | 90.4 | null |
1,353,897 | ord_dataset-6034127657614f02860ed057b62b882e | null | 2013-01-01T00:10:00 | true | [Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([F:15])[C:12]([N+:16]([O-])=O)=[CH:11][C:10]=1[Cl:19].[Cl-].[NH4+]>C(O)C.O.[Fe]>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[C:10]([Cl:19])=[CH:11][C:12]([NH2:16])=[C:13]([F:15])[CH:14]=1 | O=[N+]([O-])c1cc(Cl)c(Oc2ccncc2Br)cc1F | null | null | [Fe] | [Cl-] | [NH4+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | O | null | null | null | null | null | null | null | null | null | 70 | null | To a solution of 3-bromo-4-(2-chloro-5-fluoro-4-nitrophenoxy)pyridine (2.00 g, 5.75 mmol) in ethanol/water (9:1, 50 mL) was added iron powder (2.00 g, 35.8 mmol) followed by ammonium chloride (2.00 g, 37.4 mmol). The mixture was heated at 70° C. for 2 h. The reaction mixture was filtered, and the solids were washed with EtOAc. The filtrate was evaporated to dryness. The residue was taken in ethyl acetate and washed with water and dried. The solvent was evaporated to provide 4-(3-bromopyridin-4-yloxy)-5-chloro-2-fluorobenzenamine as light brownish oil (0.98 g, 53.6% yield). MS (ESI) m/z: 317.0/319.0 (M+H+). | Nc1cc(Cl)c(Oc2ccncc2Br)cc1F | null | null | null |
644,043 | ord_dataset-c975a50a7600448fabd558f4a94a3e29 | null | 2004-01-01T00:08:00 | true | C(OC([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[CH:19]=[C:18]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[CH3:26])[C:17]([C:27](=[O:45])[N:28]([CH2:30][C:31]3[CH:36]=[C:35]([C:37]([F:40])([F:39])[F:38])[CH:34]=[C:33]([C:41]([F:44])([F:43])[F:42])[CH:32]=3)[CH3:29])=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[F:40][C:37]([F:38])([F:39])[C:35]1[CH:36]=[C:31]([CH:32]=[C:33]([C:41]([F:42])([F:43])[F:44])[CH:34]=1)[CH2:30][N:28]([CH3:29])[C:27]([C:17]1[C:18]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[CH3:26])=[CH:19][C:14]([C:11]2[CH2:12][CH2:13][NH:8][CH2:9][CH:10]=2)=[N:15][CH:16]=1)=[O:45] | Cc1ccccc1-c1cc(C2=CCN(C(=O)OC(C)(C)C)CC2)ncc1C(=O)N(C)Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1 | 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 | null | A solution of 258 mg (0.407 mmol) 5-[(3,5-bis-trifluoromethyl-benzyl)-methyl-carbamoyl]-4-o-tolyl-3′,6′-dihydro-2′H-[2,4′]bipyridinyl-1′-carboxylic acid tert-butyl ester (Example 41) and 0.26 ml (3.2 mmol) trifluoroacetic acid in 2 ml dichloromethane was heated at reflux for 4 h. After cooling to room temperature the mixture was diluted with dichloromethane and washed with 1N aqueous sodium hydroxide solution. The aqueous layer was extracted with three portions of dichloromethane. The combined organic extracts were dried over sodium sulfate and concentrated. Column chromatography afforded 135 mg (62%) of the title compound as a light brown solid. | Cc1ccccc1-c1cc(C2=CCNCC2)ncc1C(=O)N(C)Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1 | null | 62.2 | null |
1,431,818 | ord_dataset-5e6956e6e8c24a168866a253f4a66c6c | null | 2014-01-01T00:05:00 | true | [Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[N:15]2[N:16]=[CH:17][C:18]([C:19](O)=[O:20])=[C:14]2[N:13]=[CH:12][C:11]=1[C:22]([N:24]1[CH2:29][CH2:28][CH:27]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH2:26][CH2:25]1)=[O:23].[CH2:36]([S:38]([NH2:41])(=[O:40])=[O:39])[CH3:37]>>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[N:15]2[N:16]=[CH:17][C:18]([C:19]([NH:41][S:38]([CH2:36][CH3:37])(=[O:40])=[O:39])=[O:20])=[C:14]2[N:13]=[CH:12][C:11]=1[C:22]([N:24]1[CH2:25][CH2:26][CH:27]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH2:28][CH2:29]1)=[O:23] | O=C(O)c1cnn2c(Nc3ccc(F)cc3Cl)c(C(=O)N3CCC(c4ccccc4)CC3)cnc12 | CCS(N)(=O)=O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | In the same manner as in Example 1, step 6 and using 7-(2-chloro-4-fluorophenylamino)-6-(4-phenylpiperidine-1-carbonyl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (115 mg, 0.23 mmol) obtained in step 2 and ethanesulfonamide (123 mg, 1.17 mmol), the title compound (53 mg, 39%) was obtained. | CCS(=O)(=O)NC(=O)c1cnn2c(Nc3ccc(F)cc3Cl)c(C(=O)N3CCC(c4ccccc4)CC3)cnc12 | null | 39.4 | null |
1,158,890 | ord_dataset-b195433d5c354ddfb6cde0d53c41910f | null | 2012-01-01T00:04:00 | true | [NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[NH:3][C:2]1=[S:10].[H-].[Na+].Cl[C:14]1[S:15][C:16]([CH:19]=[O:20])=[CH:17][N:18]=1>O1CCCC1>[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[S:10][C:14]1[S:15][C:16]([CH:19]=[O:20])=[CH:17][N:18]=1 | O=Cc1cnc(Cl)s1 | S=c1[nH]c2ccccc2[nH]1 | null | [H-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | 25 | null | 1,3-Dihydro-benzimidazole-2-thione (1.0 g, 6.66 mmol) is suspended into 50 mL of tetrahydrofuran under argon. Then, 479 mg (9.99 mmol) of sodium hydride is added. The reaction mixture is stirred at room temperature until gas evolution has ceased. 2-Chloro-1,3-thiazole-5-carbaldehyde (983 mg, 6.66 mmol) is then added and the reaction mixture is stirred at room temperature for 2 h, upon which it is filtered. The solid is washed with tetrahydrofuran and dried under reduced pressure. The residue is diluted with water and extracted twice with ethyl acetate and once with dichloromethane. The organic extracts are combined, dried on magnesium sulfate, filtered and concentrated under reduced pressure. 1.23 g of 2-(1H-benzimidazol-2-ylsulfanyl)-thiazole-5-carbaldehyde is obtained as a pale yellow powder. mp: 188° C. | O=Cc1cnc(Sc2nc3ccccc3[nH]2)s1 | null | 70.7 | null |
1,708,149 | ord_dataset-54347fcace774f89850681d6dec8009f | null | 2016-01-01T00:03:00 | true | [C:1]([O:7][CH2:8][C@H:9]([C:15]1[C:16](Br)=[C:17]2[C:22](=[CH:23][C:24]=1[CH3:25])[N:21]=[C:20]([CH3:26])[CH:19]=[CH:18]2)[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].[Cl:28][C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1.C([O-])([O-])=O.[K+].[K+]>COCCOC.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>[C:1]([O:7][CH2:8][C@@H:9]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[C:15]1[C:16]([C:32]2[CH:33]=[CH:34][C:29]([Cl:28])=[CH:30][CH:31]=2)=[C:17]2[C:22](=[CH:23][C:24]=1[CH3:25])[N:21]=[C:20]([CH3:26])[CH:19]=[CH:18]2)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3] | OB(O)c1ccc(Cl)cc1 | Cc1ccc2c(Br)c([C@@H](COC(=O)C(C)(C)C)OC(C)(C)C)c(C)cc2n1 | 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 | COCCOC | null | null | null | null | null | null | null | null | null | null | 110 | null | Pd(PPh3)4 (69 mg, 0.06 mmol) was added to a mixture (S)-2-(5-bromo-2,7-dimethylquinolin-6-yl)-2-tert-butoxyethyl pivalate (5E) (325 mg, 0.75 mmol), 4-chlorophenylboronic acid (175 mg, 1.1 mmol), K2CO3 (1.3 mL 2 M in water, 2.6 mmol) in 1,2-dimethoxyethane (10 mL). The reaction mixture was flushed with nitrogen, heated at 110° C. for 30 min under microwave, and then the volatile component was removed in vacuo. The residue was dissolved in ethyl acetate (100 mL), washed with NaHCO3 solution, water and brine, dried over Na2SO4, filtered and concentrated in vacuo. The obtained residue was purified by flash chromatography to provide the desired product (256 mg, 73%). LCMS-ESI+ (m/z): 468.3, 469.3 (M+H)+. | Cc1ccc2c(-c3ccc(Cl)cc3)c([C@@H](COC(=O)C(C)(C)C)OC(C)(C)C)c(C)cc2n1 | null | 72.9 | null |
93,077 | ord_dataset-f0d0fe3f599c471ca1c011dbbcdeeff2 | null | 1982-01-01T00:04:00 | true | [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([S:10]Cl)=[C:6]([C:12]([Cl:15])([Cl:14])[Cl:13])[CH:5]=1)([O-:3])=[O:2].[C:16]([OH:20])(=[O:19])[CH2:17][SH:18]>>[C:16]([CH2:17][S:18][S:10][C:7]1[CH:8]=[CH:9][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][C:6]=1[C:12]([Cl:15])([Cl:14])[Cl:13])([OH:20])=[O:19] | O=C(O)CS | O=[N+]([O-])c1ccc(SCl)c(C(Cl)(Cl)Cl)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | As in Example 1, 61.4 g of 4-nitro-2-trichloromethylbenzenesulfenyl chloride is reacted with 18.4 g of thioglycolic acid. After the solvent has been distilled off and the residue recrystallized from toluene, there is obtained 62 g of carboxymethyldithio-4-nitro-2-trichloromethylbenzene; m.p.: 140° C. | O=C(O)CSSc1ccc([N+](=O)[O-])cc1C(Cl)(Cl)Cl | null | 85.6 | null |
1,763,332 | ord_dataset-0b32b90cc77b4a3db47ad263e0bbc1a8 | null | 2016-01-01T00:09:00 | true | [F:1][CH:2]([F:13])[O:3][C:4]1[C:5](I)=[CH:6][C:7]([O:10][CH3:11])=[N:8][CH:9]=1.[Cl:14][C:15]1[CH:16]=[CH:17][C:18]([C:24]#[N:25])=[C:19](B(O)O)[CH:20]=1>>[Cl:14][C:15]1[CH:16]=[CH:17][C:18]([C:24]#[N:25])=[C:19]([C:5]2[C:4]([O:3][CH:2]([F:13])[F:1])=[CH:9][N:8]=[C:7]([O:10][CH3:11])[CH:6]=2)[CH:20]=1 | N#Cc1ccc(Cl)cc1B(O)O | COc1cc(I)c(OC(F)F)cn1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | 460 mg (purity 90%, 1.38 mmol) of 5-(difluoromethoxy)-4-iodo-2-methoxypyridine and 299 mg (1.65 mmol, 1.2 eq.) of 5-chloro-2-cyanophenylboronic acid in the presence of [1,1-bis(diphenylphosphino)ferrocene]palladium(II) chloride/dichloromethane monoadduct were reacted according to General Method 2A. The crude product was purified by flash chromatography (IR-50SI, petroleum ether/ethyl acetate 10-15%). Yield: 230 mg (purity 80%, 43% of theory) | COc1cc(-c2cc(Cl)ccc2C#N)c(OC(F)F)cn1 | null | null | null |
1,205,759 | ord_dataset-fb72428f30234761b4216139dc228d0c | null | 2012-01-01T00:09:00 | true | [N:1]1([C:5]([C:7]2[O:11][C:10]([S:12]([NH2:15])(=[O:14])=[O:13])=[CH:9][CH:8]=2)=[O:6])[CH2:4][CH2:3][CH2:2]1.Cl[C:17]1[CH:22]=[C:21]([O:23][C@H:24]([CH3:46])[CH2:25][O:26][C:27]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[N:20]=[C:19]([S:47][CH2:48][C:49]2[CH:54]=[CH:53][CH:52]=[C:51]([F:55])[C:50]=2[F:56])[N:18]=1>>[N:1]1([C:5]([C:7]2[O:11][C:10]([S:12]([NH:15][C:17]3[CH:22]=[C:21]([O:23][C@H:24]([CH3:46])[CH2:25][O:26][C:27]([C:40]4[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=4)([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)[C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=4)[N:20]=[C:19]([S:47][CH2:48][C:49]4[CH:54]=[CH:53][CH:52]=[C:51]([F:55])[C:50]=4[F:56])[N:18]=3)(=[O:14])=[O:13])=[CH:9][CH:8]=2)=[O:6])[CH2:4][CH2:3][CH2:2]1 | C[C@H](COC(c1ccccc1)(c1ccccc1)c1ccccc1)Oc1cc(Cl)nc(SCc2cccc(F)c2F)n1 | NS(=O)(=O)c1ccc(C(=O)N2CCC2)o1 | null | null | null | null | null | null | null | 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 subtitle compound was prepared from 5-(azetidin-1-ylcarbonyl)furan-2-sulfonamide (the product of step iii) (0.40 g) and 4-chloro-2-[[(2,3-difluorophenyl)methyl]thio]-6-[(1R)-1-methyl-2-(triphenylmethoxy)ethoxy]-pyrimidine (the product of Example 13, step iii) (0.41 g) according to the procedure outlined in Example 1, step iv). Yield: 0.25 g | C[C@H](COC(c1ccccc1)(c1ccccc1)c1ccccc1)Oc1cc(NS(=O)(=O)c2ccc(C(=O)N3CCC3)o2)nc(SCc2cccc(F)c2F)n1 | null | null | null |
1,295,946 | ord_dataset-de51ecc8d4434bacaa8bc32d7d73484c | null | 2013-01-01T00:05:00 | true | [NH:1]1[CH2:6][CH2:5][CH:4]([NH:7][C:8]([C:10]2[C:14]3[N:15]=[CH:16][N:17]=[C:18]([C:19]4[C:27]5[O:26][CH2:25][O:24][C:23]=5[CH:22]=[CH:21][C:20]=4[O:28][CH2:29][CH3:30])[C:13]=3[NH:12][CH:11]=2)=[O:9])[CH2:3][CH2:2]1.Cl[C:32]([O:34][CH2:35][CH3:36])=[O:33]>>[CH2:35]([O:34][C:32]([N:1]1[CH2:6][CH2:5][CH:4]([NH:7][C:8]([C:10]2[C:14]3[N:15]=[CH:16][N:17]=[C:18]([C:19]4[C:27]5[O:26][CH2:25][O:24][C:23]=5[CH:22]=[CH:21][C:20]=4[O:28][CH2:29][CH3:30])[C:13]=3[NH:12][CH:11]=2)=[O:9])[CH2:3][CH2:2]1)=[O:33])[CH3:36] | CCOc1ccc2c(c1-c1ncnc3c(C(=O)NC4CCNCC4)c[nH]c13)OCO2 | CCOC(=O)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 | null | null | Starting from 4-(5-ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid piperidin-4-ylamide (example A175) and ethyl chloroformate the title compound was obtained as colorless solid. | CCOC(=O)N1CCC(NC(=O)c2c[nH]c3c(-c4c(OCC)ccc5c4OCO5)ncnc23)CC1 | null | null | null |
992,836 | ord_dataset-b6d8835b0c934476a36e6149e7597487 | null | 2010-01-01T00:09:00 | true | [CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:33]([O:35]C)=[O:34])=[CH:12][C:13]=3[N:14]3[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][N:24]([CH3:26])[CH3:25])[CH2:18][C:17]4[CH:27]=[C:28]([O:31][CH3:32])[CH:29]=[CH:30][C:16]=4[C:15]=23)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1>O1CCOCC1.[OH-].[Na+]>[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:33]([OH:35])=[O:34])=[CH:12][C:13]=3[N:14]3[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][N:24]([CH3:25])[CH3:26])[CH2:18][C:17]4[CH:27]=[C:28]([O:31][CH3:32])[CH:29]=[CH:30][C:16]=4[C:15]=23)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1 | COC(=O)c1ccc2c(C3CCCCC3)c3n(c2c1)CCN(CCN(C)C)Cc1cc(OC)ccc1-3 | null | null | [Na+] | [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 | 60 | 3 | The crude methyl 14-cyclohexyl-6-[2-(dimethylamino)ethyl]-3-methoxy-5,6,7,8-tetrahydroindolo[2,1-a][2,5]benzodiazocine-11-carboxylate was dissolved in dioxane (0.06 M) and to that solution 10 eq of an aqueous solution of NaOH (2N) were added. The solution was stirred at 60° C. for 3 h. The solvent was evaporated in vacuo. The crude was then purified by automated RP-MS-HPLC (stationary phase: column Waters XTERRA prep. C18, 5 um, 19×100 mm. Mobile phase: MeCN/H2O buffered with 0.1% TFA). Fractions containing the pure compound were combined and freeze dried to afford the title compound as a white powder (28%). | COc1ccc2c(c1)CN(CCN(C)C)CCn1c-2c(C2CCCCC2)c2ccc(C(=O)O)cc21 | null | 28 | null |
1,702,269 | ord_dataset-54347fcace774f89850681d6dec8009f | null | 2016-01-01T00:03:00 | true | Br[C:2]1[C:10]2[N:9]3[CH2:11][CH2:12][NH:13][C:14](=[O:15])[C:8]3=[C:7]([CH3:16])[C:6]=2[CH:5]=[C:4]([C:17]#[N:18])[CH:3]=1.[F:19][C:20]1[CH:21]=[C:22](B(O)O)[CH:23]=[CH:24][CH:25]=1>>[F:19][C:20]1[CH:25]=[C:24]([C:2]2[C:10]3[N:9]4[CH2:11][CH2:12][NH:13][C:14](=[O:15])[C:8]4=[C:7]([CH3:16])[C:6]=3[CH:5]=[C:4]([C:17]#[N:18])[CH:3]=2)[CH:23]=[CH:22][CH:21]=1 | Cc1c2n(c3c(Br)cc(C#N)cc13)CCNC2=O | OB(O)c1cccc(F)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The title compound, grey solid (61 mg, 76%), MS (ISP) m/z=320.5 [(M+H)+], mp 226° C., was prepared in accordance with the general method of example 1 from 6-bromo-10-methyl-1-oxo-1,2,3,4-tetrahydro-pyrazino[1,2-a]indole-8-carbonitrile (intermediate 16) (76 mg, 0.25 mmol) and commercially available 3-fluoro-phenylboronic acid (45.5 mg, 0.325 mmol). | Cc1c2n(c3c(-c4cccc(F)c4)cc(C#N)cc13)CCNC2=O | null | null | null |
1,111,690 | ord_dataset-375a420ee9b042918ddca20f02df37d3 | null | 2011-01-01T00:11:00 | true | [CH2:1]([O:5][C:6]1[N:14]=[C:13]2[C:9]([N:10]=[C:11]([O:21][CH3:22])[N:12]2[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]Cl)=[C:8]([NH2:23])[N:7]=1)[CH2:2][CH2:3][CH3:4].[NH:24]1[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1>>[CH2:1]([O:5][C:6]1[N:14]=[C:13]2[C:9]([N:10]=[C:11]([O:21][CH3:22])[N:12]2[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][N:24]2[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)=[C:8]([NH2:23])[N:7]=1)[CH2:2][CH2:3][CH3:4] | C1CCCNCCC1 | CCCCOc1nc(N)c2nc(OC)n(CCCCCCl)c2n1 | null | null | null | null | null | null | null | 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 similarly to Intermediate 38 from 2-(butyloxy)-9-(5-chloropentyl)-8-(methyloxy)-9H-purin-6-amine and octahydroazocine. | CCCCOc1nc(N)c2nc(OC)n(CCCCCN3CCCCCCC3)c2n1 | null | null | null |
170,822 | ord_dataset-41558b7e18dd41999311b1762e0e13a3 | null | 1988-01-01T00:04:00 | true | [S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[NH:6][C:7](=[O:9])[CH3:8].C([Li])CCC.[Cl:15][CH:16]([C:19]1[O:24][C:23](=[O:25])[C:22]2[CH:26]=[CH:27][CH:28]=[C:29]([C:30]([F:33])([F:32])[F:31])[C:21]=2[N:20]=1)[CH2:17][CH3:18]>O1CCCC1.CCCCCC>[Cl:15][CH:16]([CH2:17][CH3:18])[C:19]([NH:20][C:21]1[C:29]([C:30]([F:31])([F:32])[F:33])=[CH:28][CH:27]=[CH:26][C:22]=1[C:23](=[O:25])[CH2:8][C:7]([NH:6][C:2]1[S:1][CH:5]=[CH:4][N:3]=1)=[O:9])=[O:24] | CC(=O)Nc1nccs1 | CCC(Cl)c1nc2c(C(F)(F)F)cccc2c(=O)o1 | null | [Li]CCCC | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | CCCCCC | null | null | null | null | null | null | null | null | null | null | null | Using the procedure of Step A of Example 6, a solution of 16.58 g of N-(2-thiazolyl)-acetamide in 340 ml of tetrahydrofuran, 155 ml of a solution of butyllithium in hexane and a solution of 17 g of the product of Step A in 170 ml of tetrahydrofuran were reacted to obtain 5.5 g of 2-[(2-chloro-1-oxo-butyl)-amino]-β-oxo-N-(2-thiazolyl)-3-trifluoromethyl-benzenepropanamide melting at 170° C. | CCC(Cl)C(=O)Nc1c(C(=O)CC(=O)Nc2nccs2)cccc1C(F)(F)F | null | 21.7 | null |
479,335 | ord_dataset-21c1b1c06c7e4e09a38b5b1c71a32e52 | null | 2000-01-01T00:10:00 | true | [NH:1]1[CH:5]=[N:4][CH:3]=[N:2]1.Cl[C:7]1[N:8]=[C:9]([NH:18][CH2:19][CH2:20][C:21]2[CH:26]=[CH:25][C:24]3[O:27][CH2:28][O:29][C:23]=3[CH:22]=2)[C:10]2[CH:15]=[C:14]([CH2:16][CH3:17])[S:13][C:11]=2[N:12]=1>>[N:1]1([C:7]2[N:8]=[C:9]([NH:18][CH2:19][CH2:20][C:21]3[CH:26]=[CH:25][C:24]4[O:27][CH2:28][O:29][C:23]=4[CH:22]=3)[C:10]3[CH:15]=[C:14]([CH2:16][CH3:17])[S:13][C:11]=3[N:12]=2)[CH:5]=[N:4][CH:3]=[N:2]1 | CCc1cc2c(NCCc3ccc4c(c3)OCO4)nc(Cl)nc2s1 | c1nc[nH]n1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Following the procedure of Example 97, the reaction of 1,2,4-triazole with 2-chloro-6-ethyl-4-(3,4-methylenedioxyphenethylamino)-thieno-[2,3-d]-pyrimidine gives 2-(1,2,4-triazol-1-yl)-6-ethyl-4-(3,4-methylenedioxyphenethylamino)-thieno-[2,3-d]-pyrimidine. | CCc1cc2c(NCCc3ccc4c(c3)OCO4)nc(-n3cncn3)nc2s1 | null | null | null |
352,679 | ord_dataset-127eb5fdd5b4402e92b51d0b55a5dcb5 | null | 1997-01-01T00:01:00 | true | [Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[C:4]([F:11])[CH:3]=1.[C:12]1([SiH:18]2[CH2:23][CH2:22][C:21](CCC=CC)([CH:24]3[CH2:29][CH2:28][CH:27](O)[CH2:26][CH2:25]3)[CH2:20][CH2:19]2)C=[CH:16][CH:15]=[CH:14][CH:13]=1>>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([O:8][C@H:27]2[CH2:26][CH2:25][C@H:24]([CH:21]3[CH2:20][CH2:19][SiH:18]([CH2:12][CH2:13][CH2:14][CH:15]=[CH2:16])[CH2:23][CH2:22]3)[CH2:29][CH2:28]2)=[O:7])=[C:4]([F:11])[CH:3]=1 | CC=CCCC1(C2CCC(O)CC2)CC[SiH](c2ccccc2)CC1 | O=C(O)c1ccc(Cl)cc1F | null | null | null | null | null | null | null | 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 general procedure of Example 31 was repeated using 4-chloro-2-fluorobenzoic acid and 4-(4-phenyl-(3-pentenyl)-4-silacyclohexyl)cyclohexanol, thereby obtaining the intended product. | C=CCCC[SiH]1CCC([C@H]2CC[C@H](OC(=O)c3ccc(Cl)cc3F)CC2)CC1 | null | null | null |
890,386 | ord_dataset-11068b1e475b4c5b82e56726ab0dddb7 | null | 2009-01-01T00:07:00 | true | [CH3:1][O:2][C:3](=[O:40])[CH:4]([C:9]1[CH:10]=[C:11]([C:26]2[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[C:28]([C:36]([F:39])([F:38])[F:37])[CH:27]=2)[CH:12]=[C:13]([O:15]C2C=CC=C(C(F)(F)F)C=2)[CH:14]=1)[CH2:5][CH:6]([CH3:8])[CH3:7].[F:41][C:42]1[CH:43]=[C:44](B(O)O)[CH:45]=[C:46]([F:48])[CH:47]=1>>[CH3:1][O:2][C:3](=[O:40])[CH:4]([C:9]1[CH:10]=[C:11]([C:26]2[CH:31]=[C:30]([C:32]([F:34])([F:33])[F:35])[CH:29]=[C:28]([C:36]([F:37])([F:38])[F:39])[CH:27]=2)[CH:12]=[C:13]([O:15][C:44]2[CH:43]=[C:42]([F:41])[CH:47]=[C:46]([F:48])[CH:45]=2)[CH:14]=1)[CH2:5][CH:6]([CH3:8])[CH3:7] | OB(O)c1cc(F)cc(F)c1 | COC(=O)C(CC(C)C)c1cc(Oc2cccc(C(F)(F)F)c2)cc(-c2cc(C(F)(F)F)cc(C(F)(F)F)c2)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The title compound was prepared in 15% yield from 2-[3′,5′-bis-trifluoromethyl-5-(3-trifluoromethyl-phenoxy)-biphenyl-3-yl]-4-methyl-pentanoic acid methyl ester (prepared in Example C) and 3,5-difluoro-phenylboronic acid under the conditions described in Example 15, step (g). | COC(=O)C(CC(C)C)c1cc(Oc2cc(F)cc(F)c2)cc(-c2cc(C(F)(F)F)cc(C(F)(F)F)c2)c1 | null | 15 | null |
1,444,867 | ord_dataset-275a3da8f45f4536ad29727f0ef9ba66 | null | 2014-01-01T00:06:00 | true | C(OC([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][NH:15][C:16]([C:18]2[CH:41]=[CH:40][C:21]3[N:22]([CH2:36][CH2:37][O:38][CH3:39])[C:23]([NH:25][C:26]4[S:27][C:28]5[CH:34]=[C:33]([Cl:35])[CH:32]=[CH:31][C:29]=5[N:30]=4)=[N:24][C:20]=3[CH:19]=2)=[O:17])[CH2:10][CH2:9]1)=O)(C)(C)C>Cl.O1CCOCC1>[ClH:35].[ClH:35].[NH:8]1[CH2:13][CH2:12][CH:11]([CH2:14][NH:15][C:16]([C:18]2[CH:41]=[CH:40][C:21]3[N:22]([CH2:36][CH2:37][O:38][CH3:39])[C:23]([NH:25][C:26]4[S:27][C:28]5[CH:34]=[C:33]([Cl:35])[CH:32]=[CH:31][C:29]=5[N:30]=4)=[N:24][C:20]=3[CH:19]=2)=[O:17])[CH2:10][CH2:9]1 | COCCn1c(Nc2nc3ccc(Cl)cc3s2)nc2cc(C(=O)NCC3CCN(C(=O)OC(C)(C)C)CC3)ccc21 | null | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1COCCO1 | null | null | null | null | null | null | null | null | null | null | null | null | 2-(6-Chloro-benzothiazol-2-ylamino)-1-(2-methoxy-ethyl)-1H-benzoimidazole-5-carboxylic acid (piperidin-4-ylmethyl)-amide dihydrochloride (145 mg) was prepared by following General Procedure L starting from 4-({[2-(6-chloro-benzothiazol-2-ylamino)-1-(2-methoxy-ethyl)-1H-benzoimidazole-5-carbonyl]-amino}-methyl)piperidine-1-carboxylic acid tert-butyl ester (160 mg) in 4M HCl in dioxane (2 mL). | COCCn1c(Nc2nc3ccc(Cl)cc3s2)nc2cc(C(=O)NCC3CCNCC3)ccc21 | null | 284.8 | null |
486,940 | ord_dataset-7b02d32cc502407f94aea8e5caf405a2 | null | 2000-01-01T00:12:00 | true | [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([N:10]3[CH2:15][CH2:14][CH2:13][CH2:12][C@H:11]3[C:16]([O:18]CC3C=CC=CC=3)=[O:17])=[N:7][C:6]=2[CH:26]=1.[OH-].[Li+]>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([N:10]3[CH2:15][CH2:14][CH2:13][CH2:12][C@H:11]3[C:16]([OH:18])=[O:17])=[N:7][C:6]=2[CH:26]=1 | O=C(OCc1ccccc1)[C@@H]1CCCCN1c1nc2cc(Cl)ccc2o1 | null | null | [Li+] | [OH-] | null | null | null | null | 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 by a similar method to Preparation 3 from benzyl (2S)-1-(5-chloro-1,3-benzoxazol-2-yl)-2-piperidinecarboxylate [see Preparation 28] and 1N aqueous lithium hydroxide solution to afford (2S)-1-(5-chloro-1,3-benzoxazol-2-yl)-2-piperidinecarboxylic acid as an oil. | O=C(O)[C@@H]1CCCCN1c1nc2cc(Cl)ccc2o1 | null | null | null |
106,140 | ord_dataset-e7e9fe3dd42b4f499d5b17fe63bbf336 | null | 1983-01-01T00:06:00 | true | [OH:1][CH2:2][C:3]1[O:9][C:6]([CH:7]=O)=[CH:5][CH:4]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Cl)(Cl)(Cl)[Cl:30]>>[Cl:30][CH2:7][C:6]1[O:9][C:3]([CH:2]=[O:1])=[CH:4][CH:5]=1 | ClC(Cl)(Cl)Cl | O=Cc1ccc(CO)o1 | null | c1ccc(P(c2ccccc2)c2ccccc2)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 | A mixture of 5-hydroxymethylfurfuraldehyde (0.5 g, 4 mmol) and triphenylphosphine (1.3 g, 5 mmol) in dry carbon tetrachloride (3 ml) was heated at reflux for 30 min and then filtered to give an unstable 1 M solution of 5-chloromethylfurfuraldehyde. | O=Cc1ccc(CCl)o1 | null | null | null |
93,090 | ord_dataset-f0d0fe3f599c471ca1c011dbbcdeeff2 | null | 1982-01-01T00:04:00 | true | [N:1]([O-])=O.[Na+].[CH3:5][N:6]([CH2:8][CH2:9][CH:10]([C:16]1[CH:25]=[CH:24][C:19](C(NN)=O)=[CH:18][CH:17]=1)[C:11]1[NH:12][CH:13]=[CH:14][N:15]=1)[CH3:7].C(=O)([O-])[O-].[Na+].[Na+]>O.Cl>[NH2:1][C:19]1[CH:24]=[CH:25][C:16]([CH:10]([C:11]2[NH:12][CH:13]=[CH:14][N:15]=2)[CH2:9][CH2:8][N:6]([CH3:7])[CH3:5])=[CH:17][CH:18]=1 | O=N[O-] | CN(C)CCC(c1ccc(C(=O)NN)cc1)c1ncc[nH]1 | null | Cl | O=C([O-])[O-] | [Na+] | 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 | 0.5 | A solution of sodium nitrite (0.5 g) in water (5 ml) was added dropwise to a stirred solution of 4-[3-(N,N-dimethylamino)-1-(imidazol-2-yl)propyl]benzoic acid hydrazide (2.0 g) in 2 N hydrochloric acid (10.5 ml) and water (50 ml) at 0° to 5° C. After 30 min. the solution was basified by adding 2 N sodium carbonate (15 ml) and then extracted with ether (3×50 ml). The extracts were dried (Na2SO4) and concentrated to an off white solid (1.7 g). This solid was dissolved in toluene (40 ml) and benzyl alcohol (1.5 ml) and heated on a steam bath for 2 h. Solvent was removed and the residue taken up in ethanol (20 ml) and hydrogenated at atmospheric pressure over 10% palladium oxide on charcoal (0.5 g) for 3 h. The catalyst was filtered off and the filtrate treated with a solution of maleic acid (1.8 g) in ethanol (10 ml). Removal of the solvent and trituration of the residue with dry ether afforded a white solid. Recrystallisation from ethanolether gave the trimaleate salt of the title compound, m.p. 132°-133° (2.6 g). | CN(C)CCC(c1ccc(N)cc1)c1ncc[nH]1 | null | null | null |
88,579 | ord_dataset-6dbd68e494f94ae796187f53698183da | null | 1981-01-01T00:11:00 | true | [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[CH2:17][CH2:18][N:19]1[CH2:24][CH2:23][N:22]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:21][CH2:20]1>CS(C)=O.[OH-].[Na+]>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([O:15][CH2:17][CH2:18][N:19]2[CH2:24][CH2:23][N:22]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH2:21][CH2:20]2)=[CH:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1 | ClCCN1CCN(c2ccccc2)CC1 | Oc1ccc(OCc2ccccc2)cc1 | null | [Na+] | [OH-] | 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 | 26.25 ml 4 N NaOH (0.105 mol) was added to a stirred mixture of 21.0 g (0.105 mol) 4-benzyloxyphenol and 22.5 g (0.1 mol) of 1-(2-chloroethyl)-4-phenylpiperazine in 250 ml DMSO and the reaction was heated at 60° for 60 min. After cooling, the stirred mixture was diluted with 50 ml 1 N NaOH solution and the resulting crystalline precipitate was collected by filtration and washed with water to give, after drying in vacuo, essentially pure end product, mp 116°-119°. | c1ccc(COc2ccc(OCCN3CCN(c4ccccc4)CC3)cc2)cc1 | null | null | null |
785,194 | ord_dataset-4ad5db8537994579bef51f16dd8bf0bd | null | 2007-01-01T00:08:00 | true | C([O:14][C:15]1[C:16]2[C:44](=[O:45])[N:43]([CH2:46][C:47]3[CH:52]=[CH:51][C:50]([F:53])=[CH:49][CH:48]=3)[CH2:42][C:17]=2[C:18]([O:25][S:26]([CH2:29][CH2:30][N:31]2[C:39](=[O:40])[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[C:32]2=[O:41])(=[O:28])=[O:27])=[C:19]2[C:24]=1[N:23]=[CH:22][CH:21]=[CH:20]2)(C1C=CC=CC=1)C1C=CC=CC=1.[F:54][C:55]([F:60])([F:59])[C:56]([OH:58])=[O:57].C([SiH](CC)CC)C>ClCCl>[F:53][C:50]1[CH:49]=[CH:48][C:47]([CH2:46][N:43]2[C:44](=[O:45])[C:16]3[C:15]([OH:14])=[C:24]4[C:19]([CH:20]=[CH:21][CH:22]=[N:23]4)=[C:18]([O:25][S:26]([CH2:29][CH2:30][N:31]4[C:39](=[O:40])[C:38]5[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=5)[C:32]4=[O:41])(=[O:28])=[O:27])[C:17]=3[CH2:42]2)=[CH:52][CH:51]=1.[C:56]([OH:58])([C:55]([F:60])([F:59])[F:54])=[O:57] | O=C1c2c(c(OS(=O)(=O)CCN3C(=O)c4ccccc4C3=O)c3cccnc3c2OC(c2ccccc2)c2ccccc2)CN1Cc1ccc(F)cc1 | null | null | CC[SiH](CC)CC | 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 | 0.5 | To a solution of 268 (12.2 mg, 0.017 mmol) dissolved in dichloromethane (1 mL) was added trifluoroacetic acid (100 μl) and triethylsilane (200 μl). The reaction mixture was stirred at room temperature for ½ hours under an inert atmosphere then concentrated in vacuo. The residue was triturated with diethyl ether/hexane (1/1) to afford 2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethanesulfonic acid 7-(4-fluoro-benzyl)-9-hydroxy-8-oxo-7,8-dihydro-6H-pyrrolo[3,4-g]quinolin-5-yl ester 269, TFA salt, (9.0 mg, 76%) as a yellow solid: 1H NMR (CDCl3) δ 9.0 (d, 1H), 8.5 (dd, 1H), 7.9 (m, 2H), 7.8 (m, 2H), 7.7 (m, 1H), 7.3 (m, 2H), 7.0 (t, 2H), 4.8 (s, 2H), 4.6 (s, 2H), 4.4 (q, 2H), 3.9 (q, 2H); MS: 562 (M+1). | O=C1c2c(c(OS(=O)(=O)CCN3C(=O)c4ccccc4C3=O)c3cccnc3c2O)CN1Cc1ccc(F)cc1 | null | null | null |
457,216 | ord_dataset-2501595af7f242268dbaab34c9e7ae56 | null | 2000-01-01T00:02:00 | true | [CH2:1]([SH:5])[CH2:2][CH2:3][SH:4].C(=O)([O-])[O-].[K+].[K+].F[C:13]1[CH:18]=[CH:17][C:16]([C:19](=[O:33])[C:20]([N:30]([CH3:32])[CH3:31])([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:21][CH3:22])=[CH:15][CH:14]=1>CC(N(C)C)=O>[SH:4][CH2:3][CH2:2][CH2:1][S:5][C:13]1[CH:14]=[CH:15][C:16]([C:19](=[O:33])[C:20]([N:30]([CH3:32])[CH3:31])([CH2:23][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH2:21][CH3:22])=[CH:17][CH:18]=1 | CCC(Cc1ccccc1)(C(=O)c1ccc(F)cc1)N(C)C | SCCCS | null | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(=O)N(C)C | null | null | null | null | null | null | null | null | null | null | 50 | 12 | 32.5 g (0.3 mol) of 1,3-propanedithiol are dissolved in 50 ml of dry dimethylacetamide, and the solution is heated to about 50° C. together with 13.8 g (0.1 mol) of potassium carbonate. 15.0 g (0.05 mol) of 1-(4-fluorophenyl)-2-dimethylamino-2-benzyl-butan-1-one in 30 ml of dry dimethylacetamide are added dropwise. The suspension is stirred at 50° C. overnight (about 12 hours), then the solid is filtered off. The excess 1,3-propanedithiol and dimethylacetamide are distilled off. To the residue is added toluene, then the precipitate is filtered off. After distilling off the toluene, the residue is purified by means of column chromatography on silica gel with ethyl acetate-hexane (1:7) as an eluent, and an oily product is obtained. The structure is confirmed by the 1H-NMR spectrum (CDCl3): δ [ppm]: 0.68 (t, 3H), 1.39 (t, 1H), 1.79-1.88 (m, 1H), 1.97-2.11 (m, 3H), 2.36 (s, 6H), 2.69 (q, 2H), 3.12 (t, 2H), 3.19 (s, 2H), 7.15-7.27 (m, 7H), 8.28 (d, 2H). | CCC(Cc1ccccc1)(C(=O)c1ccc(SCCCS)cc1)N(C)C | null | null | null |
1,015,915 | ord_dataset-f024e9664ab64906a71a2ff6004cb3d0 | null | 2010-01-01T00:12:00 | true | [F:1][C:2]([F:28])([F:27])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[S:10][C:11]([CH2:25][OH:26])=[C:12]([CH2:14][N:15]3[CH2:20][CH2:19][CH:18]([C:21]([F:24])([F:23])[F:22])[CH2:17][CH2:16]3)[N:13]=2)=[CH:5][CH:4]=1.[H-].[Na+].[F:31][CH:32]([F:43])[O:33][C:34]1[CH:41]=[C:40](F)[CH:39]=[CH:38][C:35]=1[C:36]#[N:37].O>CN(C)C=O>[F:31][CH:32]([F:43])[O:33][C:34]1[CH:41]=[C:40]([O:26][CH2:25][C:11]2[S:10][C:9]([C:6]3[CH:7]=[CH:8][C:3]([C:2]([F:1])([F:27])[F:28])=[CH:4][CH:5]=3)=[N:13][C:12]=2[CH2:14][N:15]2[CH2:20][CH2:19][CH:18]([C:21]([F:22])([F:24])[F:23])[CH2:17][CH2:16]2)[CH:39]=[CH:38][C:35]=1[C:36]#[N:37] | OCc1sc(-c2ccc(C(F)(F)F)cc2)nc1CN1CCC(C(F)(F)F)CC1 | N#Cc1ccc(F)cc1OC(F)F | null | [H-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CN(C)C=O | null | null | null | null | null | null | null | null | null | 5 | 0.5 | To a solution of 3 g of [2-(4-trifluoromethyl-phenyl)-4-(4-trifluoromethyl-piperidin-1-ylmethyl)-thiazol-5-yl]-methanol in 12 mL of dimethylformamide at 5° C. was added 319 mg of a 55% suspension of sodium hydride in mineral oil. The resulting mixture was stirred for 30 minutes at 5° C. 4.7 mL of the resulting solution was slowly added to a solution 319 mg of 2-difluoromethoxy-4-fluoro-benzonitrile in 1.2 mL of dimethylformamide at 5° C. The resulting mixture was stirred at 5° C. allowing the temperature to warm up to room temperature. It was then heated in a sealed tube to 60° C. under microwave irradiation for 15 minutes. After allowing it to cool down to room temperature, the mixture was poured into water and extracted with dichloromethane. The organic extracts were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (gradient from heptane 100 to heptane 50/ethyl acetate 50) to give 0.83 g of 2-difluoromethoxy-4-[2-(4-trifluoromethyl-phenyl)-4-(4-trifluoromethyl-piperidin-1-ylmethyl)-thiazol-5-ylmethoxy]-benzonitrile. | N#Cc1ccc(OCc2sc(-c3ccc(C(F)(F)F)cc3)nc2CN2CCC(C(F)(F)F)CC2)cc1OC(F)F | null | 82.3 | null |
1,117,487 | ord_dataset-4226e9b4f9f845db967ed997270dcafc | null | 2011-01-01T00:12:00 | true | C([N:4]1[C:46]2[C:41](=[CH:42][CH:43]=[C:44]([Cl:47])[CH:45]=2)[C:6]2([CH:11]([C:12]3[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:13]=3[O:19][C:20]([CH2:30][CH3:31])([CH2:28][CH3:29])[C:21]([NH:23][S:24]([CH3:27])(=[O:26])=[O:25])=[O:22])[CH2:10][C:9](=[S:32])[NH:8][CH:7]2[C:33]2[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:34]=2[CH3:40])[C:5]1=[O:48])(=O)C.C([O-])([O-])=O.[K+].[K+]>CO>[Cl:47][C:44]1[CH:45]=[C:46]2[NH:4][C:5](=[O:48])[C:6]3([CH:11]([C:12]4[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:13]=4[O:19][C:20]([CH2:30][CH3:31])([CH2:28][CH3:29])[C:21]([NH:23][S:24]([CH3:27])(=[O:25])=[O:26])=[O:22])[CH2:10][C:9](=[S:32])[NH:8][CH:7]3[C:33]3[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:34]=3[CH3:40])[C:41]2=[CH:42][CH:43]=1 | CCC(CC)(Oc1ccc(Cl)cc1C1CC(=S)NC(c2cc(F)ccc2C)C12C(=O)N(C(C)=O)c1cc(Cl)ccc12)C(=O)NS(C)(=O)=O | null | null | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | 25 | 0.25 | A mixture of chiral (2′S, 3S, 4′R)-1-acetyl-6-chloro-4′-[5-chloro-2-(2-methanesulfonylamino-1,1-diethyl-2-oxo-ethoxy)-phenyl]-2′-(5-fluoro-2-methyl-phenyl)-6′-thioxo spiro[3H-indole-3,3′-piperidine]-2(1H)-one (45 mg) and K2CO3 (30 mg) in methanol (2 mL) was stirred at room temperature for 15 min, and then the mixture was partitioned between ethyl acetate and diluted aqueous HCl solution. The organic layer was washed with brine, dried over anhydrous Na2SO4, concentrated to give the title compound as white solid (35 mg). | CCC(CC)(Oc1ccc(Cl)cc1C1CC(=S)NC(c2cc(F)ccc2C)C12C(=O)Nc1cc(Cl)ccc12)C(=O)NS(C)(=O)=O | null | 82.5 | null |
847,080 | ord_dataset-e2b35e721c2741999b0005d12691f9fe | null | 2008-01-01T00:10:00 | true | O.[OH-].[Li+].Cl.[CH3:5][O:6][C:7](=[O:11])[CH2:8][CH2:9][NH2:10].Br[CH2:13][C:14]1[CH:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:15]=1[N+:21]([O-:23])=[O:22]>CN(C)C=O>[CH3:5][O:6][C:7](=[O:11])[CH2:8][CH2:9][NH:10][CH2:13][C:14]1[CH:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:15]=1[N+:21]([O-:23])=[O:22] | O=[N+]([O-])c1ccc(Cl)cc1CBr | COC(=O)CCN | null | Cl | [Li+] | [OH-] | 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 | 25 | 0.33 | A mixture of 4 Å molecular sieve powder (16.9 g) and lithium hydroxide monohydrate (1.80 g, 43 mmol) in N,N-dimethylformamide (100 ml) was stirred at room temperature for 20 minutes. β-Alanine methyl ester hydrochloride (5.0 g, 35.8 mmol) was added and the mixture stirred for a further 45 minutes. 2-(Bromomethyl)-4-chloro-1-nitrobenzene (J. Het. Chem. 1972; 9(1), 119-22) (8.98 g, 35.8 mmol) was added and the reaction stirred at room temperature for 16 hours. The mixture was filtered, the filtrate diluted with ethyl acetate (150 ml), then washed with brine (3×150 ml) and extracted with 2N hydrochloric acid (2×75 ml). The combined acidic extracts were basified using sodium carbonate, then extracted with ethyl acetate. The combined organic extracts were dried over magnesium sulphate and evaporated under reduced pressure to afford the title compound, 1.29 g. | COC(=O)CCNCc1cc(Cl)ccc1[N+](=O)[O-] | null | null | null |
992,615 | ord_dataset-b6d8835b0c934476a36e6149e7597487 | null | 2010-01-01T00:09:00 | true | Cl.[F:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[NH:9][C:10]1[O:14][C:13]([C:15]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([C@H:24]3[CH2:29][CH2:28][C@H:27]([CH2:30][NH:31]C(=O)OC(C)(C)C)[CH2:26][CH2:25]3)=[CH:20][CH:19]=2)=[O:16])=[N:12][N:11]=1>O1CCOCC1>[NH2:31][CH2:30][C@H:27]1[CH2:28][CH2:29][C@H:24]([C:21]2[CH:20]=[CH:19][C:18]([NH:17][C:15]([C:13]3[O:14][C:10]([NH:9][C:4]4[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=4[F:2])=[N:11][N:12]=3)=[O:16])=[CH:23][CH:22]=2)[CH2:25][CH2:26]1 | CC(C)(C)OC(=O)NC[C@H]1CC[C@H](c2ccc(NC(=O)c3nnc(Nc4ccccc4F)o3)cc2)CC1 | null | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1COCCO1 | null | null | null | null | null | null | null | null | null | null | null | 18 | 4M HCl in 1,4-dioxane (1 mL) was added to tert-butyl [(trans-4-{4-[({5-[(2-fluorophenyl)amino]-1,3,4-oxadiazol-2-yl}carbonyl)amino]phenyl}cyclohexyl)-methyl]carbamate (Example 618) (50 mg, 0.10 mmol) and the suspension stirred for 18 hours. All volatiles were removed in vacuo and the residue triturated with Et2O (3 mL), the solid filtered, washed with Et2O (2×5 mL), isohexane (2×5 mL) to give the title compound (as a hydrochloride salt) (44 mg, 99%) as a white solid; 1H NMR δ 1.07-1.16 (2H, m), 1.39-1.47 (2H, m), 1.57-1.69 (1H, m), 1.87 (4H, t), 2.41-2.52 (1H, m), 2.71 (2H, d), 7.14-7.20 (1H, m), 7.23 (1H, s), 7.25-7.27 (2H, m), 7.29-7.34 (1H, m), 7.70 (2H, d), 7.87 (3H, s), 8.01-8.06 (1H, m), 10.76 (1H, s), 10.94 (1H, s); MS m/e (MH)+ 410. | NC[C@H]1CC[C@H](c2ccc(NC(=O)c3nnc(Nc4ccccc4F)o3)cc2)CC1 | null | null | null |
898,564 | ord_dataset-de6bce51790e4004a27e1a8f2bcc7ded | null | 2009-01-01T00:08:00 | true | [N:1]1([C:7](=[O:15])[CH2:8][N:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C(=O)(O)[O-].[Na+].[C:21](Cl)([Cl:23])=[O:22]>ClCCl>[N:1]1([C:7](=[O:15])[CH2:8][N:9]2[CH2:10][CH2:11][N:12]([C:21]([Cl:23])=[O:22])[CH2:13][CH2:14]2)[CH2:2][CH2:3][O:4][CH2:5][CH2:6]1 | O=C(Cl)Cl | O=C(CN1CCNCC1)N1CCOCC1 | null | O=C([O-])O | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | 0 | 0.5 | To the solution of 1-morpholin-4-yl-2-piperazin-1-yl-ethanone (0.5 g, 2.34 mmol) (Oakwood) in dichloromethane (15 mL) was added saturated sodium bicarbonate solution (15 mL). The reaction mixture was cooled to 0° C. and then followed by the dropwise addition of phosgene (20% in toluene, 2.22 mL, 4.21 mmol). The reaction mixture was allowed to warm up to room temperature. After stirring at room temperature for 30 minutes, the reaction mixture was extracted with dichloromethane three times. The combined organic layer was washed with water and brine, dried (Na2SO4), filtered and concentrated to give crude 4-(2-morpholin-4-yl-2-oxo-ethyl)-piperazine-1-carbonyl chloride as yellow oil and used for the next step without further purification. | O=C(Cl)N1CCN(CC(=O)N2CCOCC2)CC1 | null | null | null |
952,819 | ord_dataset-3feb2a95f66e4706a4a50c977ccd9bf8 | null | 2010-01-01T00:04:00 | true | [CH2:1]([C:3]1[CH:4]=[C:5]([CH2:11][C@@H:12]([NH:16][C:17]([N:19]2[CH2:24][CH2:23][CH:22]([N:25]3[CH2:31][CH2:30][C:29]4[CH:32]=[CH:33][CH:34]=[CH:35][C:28]=4[NH:27][C:26]3=[O:36])[CH2:21][CH2:20]2)=[O:18])[C:13](O)=[O:14])[CH:6]=[CH:7][C:8]=1[CH2:9][CH3:10])[CH3:2].[CH3:37][N:38]1[CH2:44][CH2:43][CH2:42][N:41]([CH:45]2[CH2:50][CH2:49][NH:48][CH2:47][CH2:46]2)[CH2:40][CH2:39]1>>[CH2:1]([C:3]1[CH:4]=[C:5]([CH:6]=[CH:7][C:8]=1[CH2:9][CH3:10])[CH2:11][C@@H:12]([NH:16][C:17]([N:19]1[CH2:24][CH2:23][CH:22]([N:25]2[CH2:31][CH2:30][C:29]3[CH:32]=[CH:33][CH:34]=[CH:35][C:28]=3[NH:27][C:26]2=[O:36])[CH2:21][CH2:20]1)=[O:18])[C:13]([N:48]1[CH2:49][CH2:50][CH:45]([N:41]2[CH2:42][CH2:43][CH2:44][N:38]([CH3:37])[CH2:39][CH2:40]2)[CH2:46][CH2:47]1)=[O:14])[CH3:2] | CCc1ccc(C[C@@H](NC(=O)N2CCC(N3CCc4ccccc4NC3=O)CC2)C(=O)O)cc1CC | CN1CCCN(C2CCNCC2)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 analogously to Example 9i) from 400 mg (0.81 mmol) (R)-3-(3,4-diethyl-phenyl)-2-{[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid and 200 mg (1.01 mmol) 1-methyl-4-piperidin-4-yl-[1,4]diazepan. | CCc1ccc(C[C@@H](NC(=O)N2CCC(N3CCc4ccccc4NC3=O)CC2)C(=O)N2CCC(N3CCCN(C)CC3)CC2)cc1CC | null | null | null |
595,392 | ord_dataset-278fb6af8a994ac69e4d95e6e6eff756 | null | 2003-01-01T00:05:00 | true | [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][NH2:8].[CH2:9]([O:11][C:12](=[O:19])[CH:13]([CH:17]=O)[C:14](=O)[CH3:15])[CH3:10].N1C=CC=CC=1>C(O)C>[CH2:9]([O:11][C:12]([C:13]1[C:14]([CH3:15])=[N:8][N:7]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)[CH:17]=1)=[O:19])[CH3:10] | NNc1ccccn1 | CCOC(=O)C(C=O)C(C)=O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | c1ccncc1 | null | null | null | null | null | null | null | null | null | null | null | Similar to Example 1, equimolar amounts of 2-pyridylhydrazine and 2-formyl-3-oxo-butyric acid ethyl ester were combined in a solution of 50% pyridine in ethanol. Analysis showed that the resulting solid was determined to be the named product (m.p. 49° C.-50° C.). | CCOC(=O)c1cn(-c2ccccn2)nc1C | null | null | null |
166,586 | ord_dataset-5c25f386f4664070a72d578feacedf86 | null | 1987-01-01T00:12:00 | true | [CH2:1]([O:8][C:9]([NH:11][C@@H:12]([C:14]([OH:16])=[O:15])[CH3:13])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:17][C@@H:18]1[CH2:23][CH2:22][CH2:21][CH2:20][C@H:19]1O.C1CCC(N=C=NC2CCCCC2)CC1>C1COCC1.CN(C)C1C=CN=CC=1.CC(O)=O>[CH3:17][C@@H:18]1[CH2:23][CH2:22][CH2:21][CH2:20][C@H:19]1[O:15][C:14](=[O:16])[C@@H:12]([CH3:13])[NH:11][C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:10] | C[C@@H]1CCCC[C@H]1O | C[C@@H](NC(=O)OCc1ccccc1)C(=O)O | null | C(=NC1CCCCC1)=NC1CCCCC1 | CN(C)c1ccncc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(=O)O | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | null | N-Benzyloxycarbonyl-D-alanine (2.5 mmol. 0.556 g) and trans-2-methylcyclohexanol (3 equivalents, 1 mL) were dissolved in 7 mL THF at room temperature, followed by the addition of 70 mg 4-dimethylaminopyridine. DCC (2.5 mmol, 0.515 g) was then introduced with stirring. The solution turned cloudy immediately and was stirred at room temperature overnight. The reaction mixture was stirred for another 15 min after several drops of HOAc were added to it. Dicyclohexylurea (DCU) was filtered off and the filtrate evaporated to dryness. The residue was dissolved in ethyl acetate. The EtOAc solution was filtered, washed with 0.5N HCl (2×), brine (2×), 5% NaHCO3 (2×) and finally brine (2×). The organic phase, after being dried over anhydrous Na2SO4, showed one UV-positive tlc spot. A second spot, which could only be detected by phosphomolybdic acid (PMA)--Ce(SO4)2 spray, was identified as the unreacted alcohol by tlc comparison with authentic material. The ethyl acetate solution was evaporated to dryness and dried under high vacuum, giving a clear oil weighing 0.965 g. The crude material was chromatographed on a Merck Si--60 size C prepacked column by gradient elution with toluene to toluene:ethyl acetate (9:1). After evaporation, 0.629 g (72.0%) of clear, colorless oil was recovered: nmr (CDCl3, ppm), 0.85-2.05 (13H, m, aliphatic H of cyclohexanol), 0.9 (3H, d, J=6 Hz, CH3) 1.3 (3H, d, J=7 Hz, obscured by other aliphatic protons, β--CH3 of Ala), 4.3 (2H, m, CH--O-- and α--H), 5 (2H, s, ArCH2 --), 5.25 (1H, broad s, amide H), 7.15 (5H, s, ArH5). | C[C@@H]1CCCC[C@H]1OC(=O)[C@@H](C)NC(=O)OCc1ccccc1 | null | null | null |
1,055,337 | ord_dataset-373415d3e0e54004837cf4831e67666f | null | 2011-01-01T00:05:00 | true | [CH3:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[C:11]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[N:12][O:13][C:14]=2[CH3:15])[N:5]=[N:4][C:3]=1[C:22]([OH:24])=O.[CH:25]1([NH2:28])[CH2:27][CH2:26]1>>[CH:25]1([NH:28][C:22]([C:3]2[N:4]=[N:5][C:6]([O:8][CH2:9][C:10]3[C:11]([C:16]4[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=4)=[N:12][O:13][C:14]=3[CH3:15])=[CH:7][C:2]=2[CH3:1])=[O:24])[CH2:27][CH2:26]1 | NC1CC1 | Cc1cc(OCc2c(-c3ccccc3)noc2C)nnc1C(=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 | As described for example 44, 4-methyl-6-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-pyridazine-3-carboxylic acid (200 mg, 0.61 mmol) was converted, using cyclopropylamine instead of 4-amino-tetrahydropyran, to the title compound (SiO2, heptane:ethyl acetate=100:0 to 60:40, 122 mg, 54%) which was obtained as a white solid. MS: m/e=365.3 [M+H]−. | Cc1cc(OCc2c(-c3ccccc3)noc2C)nnc1C(=O)NC1CC1 | null | 54 | null |
1,441,743 | ord_dataset-275a3da8f45f4536ad29727f0ef9ba66 | null | 2014-01-01T00:06:00 | true | [CH2:1]([C:3]1[CH:4]=[N:5][C:6]([N:9]2[CH2:14][CH2:13][CH:12]([N:15]3[CH2:19][CH2:18][C@H:17]([NH:20]C(=O)OC(C)(C)C)[C:16]3=[O:28])[CH2:11][CH2:10]2)=[N:7][CH:8]=1)[CH3:2]>C(O)(C(F)(F)F)=O.C(Cl)Cl>[NH2:20][C@H:17]1[CH2:18][CH2:19][N:15]([CH:12]2[CH2:13][CH2:14][N:9]([C:6]3[N:7]=[CH:8][C:3]([CH2:1][CH3:2])=[CH:4][N:5]=3)[CH2:10][CH2:11]2)[C:16]1=[O:28] | CCc1cnc(N2CCC(N3CC[C@H](NC(=O)OC(C)(C)C)C3=O)CC2)nc1 | 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 | null | null | A solution of (S)-tert-butyl 1-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)-2-oxopyrrolidin-3-ylcarbamate (1 g, 2.6 mmol) in 50% TFA/CH2Cl2 (10 mL) was stirred at ambient temperature for 1 hour. The mixture was concentrated in vacuo. The residue was dissolved in CH2Cl2 (100 mL) and washed with 1N NaOH (100 mL) and brine. The combined organic layers were dried over MgSO4, filtered and concentrated in vacuo to yield (S)-3-amino-1-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)pyrrolidin-2-one (0.75 g, 2.6 mmol, 100%) | CCc1cnc(N2CCC(N3CC[C@H](N)C3=O)CC2)nc1 | null | 100 | null |
1,232,394 | ord_dataset-e96f5a2842f14e5380461c234100f05a | null | 2012-01-01T00:12:00 | true | [S-:1][C:2]#[N:3].[K+].[NH2:5][C:6]1[CH:33]=[CH:32][C:9]([O:10][C:11]2[CH:12]=[CH:13][C:14]([CH3:31])=[C:15]([NH:17][C:18](=[O:30])[C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([C:25]4([C:28]#[N:29])[CH2:27][CH2:26]4)[CH:20]=3)[CH:16]=2)=[CH:8][CH:7]=1.BrBr>C(O)(=O)C>[NH2:3][C:2]1[S:1][C:7]2[CH:8]=[C:9]([O:10][C:11]3[CH:12]=[CH:13][C:14]([CH3:31])=[C:15]([NH:17][C:18](=[O:30])[C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([C:25]5([C:28]#[N:29])[CH2:26][CH2:27]5)[CH:20]=4)[CH:16]=3)[CH:32]=[CH:33][C:6]=2[N:5]=1 | Cc1ccc(Oc2ccc(N)cc2)cc1NC(=O)c1cccc(C2(C#N)CC2)c1 | N#C[S-] | null | BrBr | [K+] | 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 | 0.17 | Potassium thiocyanate (7.00 g, 72 mmol) was suspended in acetic acid (120 mL) and the mixture was stirred at room temperature for 10 min. To the obtained solution was added a solution of N-[5-(4-aminophenoxy)-2-methylphenyl]-3-(1-cyanocyclopropyl)benzamide (6.90 g, 18 mmol) in acetic acid (120 mL), and the mixture was further stirred at room temperature for 30 min. To the obtained solution was added dropwise slowly a solution of bromine (3.60 g, 22.5 mmol) in acetic acid (80 mL) and, after the completion of the dropwise addition, the mixture was further stirred at room temperature for 12 hr. The resulting yellow insoluble material was filtered off and washed with acetic acid. The filtrate and the washing were combined and concentrated under reduced pressure. The obtained residue was suspended in ethyl acetate (400 mL), washed with 5% aqueous sodium hydrogencarbonate solution (200 mL×2) and saturated brine (200 mL), successively, and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (hexane/ethyl acetate=50/50→0/100), and the obtained solution was concentrated under reduced pressure to give the title compound (6.27 g, 79%) as a pale-yellow amorphous substance. | Cc1ccc(Oc2ccc3nc(N)sc3c2)cc1NC(=O)c1cccc(C2(C#N)CC2)c1 | null | 79.1 | null |
1,384,524 | ord_dataset-31641fb65b34430fa7435229b949b604 | null | 2014-01-01T00:01:00 | true | [NH2:1][N:2]1[N:11]=[C:10]([C:12]([F:15])([F:14])[F:13])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]1=[O:16].[CH:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:20]=[CH:19][C:18]=1[CH2:27][C:28](O)=[O:29]>>[CH:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:20]=[CH:19][C:18]=1[CH2:27][C:28]([NH:1][N:2]1[N:11]=[C:10]([C:12]([F:15])([F:13])[F:14])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]1=[O:16])=[O:29] | Nn1nc(C(F)(F)F)c2ccccc2c1=O | O=C(O)Cc1ccc2ccccc2c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The product of Example 11B and 2-napthylacetic acid were treated using a method similar to that described in Example 57 to give the title compound. 1H NMR (500 MHz, DMSO-d6/Deuterium Oxide) δ ppm 8.44 (ddd, J=8.0, 1.4, 0.6 Hz, 1H), 8.12-8.16 (m, 1H), 8.01-8.09 (m, 2H), 7.87-7.97 (m, 4H), 7.48-7.59 (m, 3H), 3.91 (s, 2H); MS (ESI−) M/Z 396 (M−H)−. | O=C(Cc1ccc2ccccc2c1)Nn1nc(C(F)(F)F)c2ccccc2c1=O | null | null | null |
1,467,269 | ord_dataset-fd1fa959d6264608b0b7fcda16741bfd | null | 2014-01-01T00:08:00 | true | C[O:2][C:3]([C:5]1([NH:14][C:15](=[O:36])[C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([O:24][CH2:25][C:26]([C:29]3[CH:34]=[CH:33][CH:32]=[C:31]([Cl:35])[CH:30]=3)([F:28])[F:27])[CH:17]=2)[CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH2:6]1)=[O:4].[OH-].[Li+].Cl>C1COCC1.O>[Cl:35][C:31]1[CH:30]=[C:29]([C:26]([F:27])([F:28])[CH2:25][O:24][C:18]2[CH:17]=[C:16]([CH:21]=[CH:20][C:19]=2[O:22][CH3:23])[C:15]([NH:14][C:5]2([C:3]([OH:4])=[O:2])[CH2:6][C:7]3[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=3)[CH2:13]2)=[O:36])[CH:34]=[CH:33][CH:32]=1 | COC(=O)C1(NC(=O)c2ccc(OC)c(OCC(F)(F)c3cccc(Cl)c3)c2)Cc2ccccc2C1 | null | null | Cl | [Li+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | O | null | null | null | null | null | null | null | null | null | 25 | 72 | 20 mg of the compound of step 3 were dissolved in 5 ml of a mixture of THF and water (9:1), and 1.9 mg (77.5 μmol) of lithium hydroxide were added. After stirring at room temperature for 3 d, the mixture was acidified with 1 M hydrochloric acid and evaporated. The residue was purified by silica gel chromatography (DCM/methanol 95:5) and RP HPLC (water/ACN gradient) to give 8 mg of the title compound. | COc1ccc(C(=O)NC2(C(=O)O)Cc3ccccc3C2)cc1OCC(F)(F)c1cccc(Cl)c1 | null | 41.1 | null |
362,759 | ord_dataset-0b24d1f58a024ed7bc2bda95b2430c72 | null | 1997-01-01T00:04:00 | true | [OH:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:12][C@@H:11]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[O:10][C:9]2=[O:19])=[CH:4][CH:3]=1.[C:20](O)(=[O:26])[CH2:21][CH2:22][CH2:23][CH2:24][CH3:25].C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C1C=CN=CC=1.C(Cl)Cl>[C:20]([O:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:12][C@@H:11]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[O:10][C:9]2=[O:19])=[CH:6][CH:7]=1)(=[O:26])[CH2:21][CH2:22][CH2:23][CH2:24][CH3:25] | CCCCCC(=O)O | O=C1O[C@H](c2ccccc2)CN1c1ccc(O)cc1 | null | C(=NC1CCCCC1)=NC1CCCCC1 | CN(C)c1ccncc1 | 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 | 0.50 g (1.96 mM) of (5R)-3-(4-hydroxyphenyl)-5-phenyl-2-oxazolidinone synthesized in Example 2, 0.26 g of hexanoic acid and 20 ml of methylene chloride were placed in 50 ml-round bottomed flask, followed by stirring to form a solution. To the solution, 0.43 g (2.08 mM) of N,N'-dicyclohexylcarbodiimide and 0.10 g of 4-dimethylaminopyridine were added in succession, followed by stirring for 8 hours at room temperature. The precipitated N,N'-dicyclohexylurea was filtered out and the filtrate was evaporated under reduced pressure to obtain a residue. The residue was purified by silica gel column chromatography (eluent: toluene/ethyl acetate=20/1) and recrystallized from methanol to obtain 0.36 g of (5R)-3-(4-hexanoyloxyphenyl)-5-phenyl-2-oxazolidinone (Yield: 52.0%). | CCCCCC(=O)Oc1ccc(N2C[C@@H](c3ccccc3)OC2=O)cc1 | null | 52 | null |
157,877 | ord_dataset-58ec6779628e43e2b3f0972725f262e6 | null | 1987-01-01T00:05:00 | true | [BH4-].[Na+].[CH3:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[N:6]2[CH2:13][CH2:14][C:15]([CH2:21][CH:22]=[CH2:23])([CH2:18][CH:19]=[CH2:20])[C:16](=[O:17])[C:5]=12>C(O)C>[CH3:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[N:6]2[CH2:13][CH2:14][C:15]([CH2:18][CH:19]=[CH2:20])([CH2:21][CH:22]=[CH2:23])[CH:16]([OH:17])[C:5]=12 | C=CCC1(CC=C)CCn2c(c(C)c3ccccc32)C1=O | null | null | [BH4-] | [Na+] | 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 | 24 | Sodium borohydride (10.53 g, 270 mmol) was added portionwise upon cooling to a solution of 6,7,8,9-tetrahydro-10-methyl-8,8-bis(2-propenyl)pyrido[1,2-a]indol-9-one (12.8 g, 45.8 mmol), in ethanol (350 mL) at 25° C. The reaction mixture was stirred at room temperature for 24 hours. The solvent was removed in vacuo to near-dryness, and the residue partitioned between water (300 mL) and ether (300 mL). The separated organic layer was washed with brine (100 mL), dried over MgSO4, filtered and evaporated to afford 12.63 g (98%) of the title compound as a light amber oil. | C=CCC1(CC=C)CCn2c(c(C)c3ccccc32)C1O | null | 98 | null |
723,675 | ord_dataset-0387783899c642a8b7eb4ba379bcdf5d | null | 2006-01-01T00:08:00 | true | [CH:1]1([CH2:4][NH:5][C:6]2[C:7]([S:25][CH3:26])=[N:8][N:9]3[C:14]([C:15]4[C:20]([CH3:21])=[CH:19][C:18]([CH3:22])=[CH:17][C:16]=4[O:23][CH3:24])=[CH:13][CH:12]=[CH:11][C:10]=23)[CH2:3][CH2:2]1.[O:27]1[CH2:32][CH2:31][CH:30]([CH:33]=O)[CH2:29][CH2:28]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>O1CCCC1.C(OCC)(=O)C>[CH:1]1([CH2:4][N:5]([C:6]2[C:7]([S:25][CH3:26])=[N:8][N:9]3[C:14]([C:15]4[C:20]([CH3:21])=[CH:19][C:18]([CH3:22])=[CH:17][C:16]=4[O:23][CH3:24])=[CH:13][CH:12]=[CH:11][C:10]=23)[CH2:33][CH:30]2[CH2:31][CH2:32][O:27][CH2:28][CH2:29]2)[CH2:2][CH2:3]1 | O=CC1CCOCC1 | COc1cc(C)cc(C)c1-c1cccc2c(NCC3CC3)c(SC)nn12 | null | CC(=O)O[BH-](OC(C)=O)OC(C)=O | O=C([O-])O | [Na+] | 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 | null | 1 | After dissolving N-cyclopropylmethyl-N-[7-(2-methoxy-4,6-dimethylphenyl)-2-(methylsulfanyl)pyrazolo[1,5-a]pyridin-3-yl]amine (100 mg) in tetrahydrofuran (2 mL), tetrahydro-2H-4-pyrancarbaldehyde (78 mg) [CAS No. 50675-18-8] and sodium triacetoxyborohydride (87 mg) were added, and the mixture was stirred for 1 hour. Saturated aqueous sodium hydrogencarbonate was added to the reaction mixture, extraction was performed with ethyl acetate, and the extract was washed with brine. After drying over anhydrous magnesium sulfate and filtration, the solvent was concentrated under reduced pressure, the residue was purified by silica gel column chromatography, and the title compound (70 mg) was obtained from the n-hexane:ethyl acetate (7:1) fraction as a yellow oil. | COc1cc(C)cc(C)c1-c1cccc2c(N(CC3CCOCC3)CC3CC3)c(SC)nn12 | null | 55.2 | null |
1,190,105 | ord_dataset-9cd817a75dfc4fe7ad19d4232772d5ff | null | 2012-01-01T00:07:00 | true | Br[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[C:5]([NH2:12])=[C:4]([N+:13]([O-:15])=[O:14])[CH:3]=1.[F:16][C:17]([F:28])([F:27])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1B(O)O>CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[N+:13]([C:4]1[C:5]([NH2:12])=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=[C:2]([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[C:17]([F:28])([F:27])[F:16])[CH:3]=1)([O-:15])=[O:14] | Nc1c([N+](=O)[O-])cc(Br)cc1C(F)(F)F | OB(O)c1ccccc1C(F)(F)F | null | Cl[Pd]Cl | [Fe+2] | c1ccc(P(c2ccccc2)[c-]2cccc2)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | CCOC(C)=O | null | null | null | null | null | null | null | null | null | 90 | 18 | 4-Bromo-2-nitro-6-trifluoromethyl-phenylamine (10.0 g, 35.2 mmol, as prepared in the previous step), 2-trifluoromethylphenylboronic acid (8.70 g, 45.8 mmol), and (dppf)PdCl2 DCM (1.44 g, 1.76 mmol) were placed in a 500 mL round-bottom flask equipped with a magnetic stir bar and reflux condenser. The flask was evacuated and backflushed with Ar. DME (150 mL) and 2M aq Na2 CO3 (50.0 mL, 100 mmol) were added via cannula. The mixture was stirred at 90° C. for 18 h. The mixture was cooled to RT, diluted with EtOAc (100 mL), then washed with water (100 mL) and brine (100 mL). The combined aqueous layers were extracted twice with EtOAc (50 mL). The combined organic extracts were dried over MgSO4, filtered, and the solvent was removed under reduced pressure. The residue was purified on an 80-g pre-packed SiO2 column eluting with EtOAc/hexanes, 0:1 to 1:4, v/v over 30 min, yielding 11.3 g (92%) of the title compound. 1H-NMR (400 MHz, CDCl3) δ: 8.35 (d, J=2.0 Hz, 1H), 7.78 (d, J=7.8 Hz, 1H), 7.74 (s, 1H), 7.61 (t, J=7.2 Hz, 1H), 7.53 (t, J=7.6 Hz, 1H), 7.33 (d, J=7.6 Hz, 1H), 6.75 (br. s., 2H). | Nc1c([N+](=O)[O-])cc(-c2ccccc2C(F)(F)F)cc1C(F)(F)F | null | 92 | null |
558,631 | ord_dataset-f483e698250b4da0a84f425c7bfa965a | null | 2002-01-01T00:08:00 | true | Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1)[C:6]([N:19]([C:22]1[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=1)[CH:20]=[O:21])=[C:5]2[O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.[Li]CCCC.[CH3:41][C:42]([CH3:44])=[O:43].[NH4+].[Cl-]>C1COCC1>[F:18][C:15]1[CH:16]=[CH:17][C:12]([CH2:11][N:7]2[C:8]3[C:4](=[CH:3][C:2]([C:42]([OH:43])([CH3:44])[CH3:41])=[CH:10][CH:9]=3)[C:5]([O:28][CH2:29][C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)=[C:6]2[N:19]([C:22]2[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=2)[CH:20]=[O:21])=[CH:13][CH:14]=1 | CC(C)=O | O=CN(c1cccnc1)c1c(OCc2ccccc2)c2cc(Br)ccc2n1Cc1ccc(F)cc1 | null | [Cl-] | [Li]CCCC | [NH4+] | 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 | -100 | 0.5 | To a solution of 201 mg of {5-Bromo-1-[(4-fluorophenyl)methyl]-3-(phenylmethoxy)indol-2-yl}-N-(3-pyridyl)formamide in 10 mL of THF at −100° C. was added 0.5 mL of n-BuLi (1.6 M in hexanes) and the mixture was stirred at −100° C. for 30 min. To this cold solution, 190 μL of acetone was added and the reaction mixture was allowed to warm to room temperature. At this time, aqueous NH4Cl was added, the product was extracted with ethyl acetate and the organic phase was washed with brine and dried over anhydrous Na2SO4. Flash chromatography (100% hexane to hexane/ethyl acetate 1:2) and swish with CH2Cl2/hexane yielded 61 mg of the title compound as a yellow solid. | CC(C)(O)c1ccc2c(c1)c(OCc1ccccc1)c(N(C=O)c1cccnc1)n2Cc1ccc(F)cc1 | null | null | null |
1,477,355 | ord_dataset-c3c1091f873b4f40827973a6f1f9b685 | null | 2014-01-01T00:09:00 | true | [O:1]=[C:2]1[CH:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:6][CH2:5][CH2:4][NH:3]1.S(Cl)([Cl:16])(=O)=O.C(=O)([O-])O.[Na+]>C1COCC1>[Cl:16][C:7]1([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:6][CH2:5][CH2:4][NH:3][C:2]1=[O:1] | CCOC(=O)C1CCCNC1=O | O=S(=O)(Cl)Cl | null | O=C([O-])O | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | 25 | 18 | To a mixture of ethyl 2-oxopiperidine-3-carboxylate (30 g) in THF (300 mL) was added dropwise sulfuryl chloride (14.2 mL) at 0° C.-5° C., and the mixture was stirred at room temperature for 18 hr. To the reaction mixture was added saturated aqueous sodium hydrogen carbonate solution (300 mL) at 0° C., and the mixture was stirred at room temperature for 30 min and extracted with ethyl acetate (300 mL×3). The extract was washed with saturated brine (300 mL), and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was washed with hexane/ethyl acetate (5/1, 60 mL×2) to give the title compound (32.7 g). MS (ESI+): [M+H]+ 206.1. | CCOC(=O)C1(Cl)CCCNC1=O | null | null | null |
650,705 | ord_dataset-271c0b74f4794a06992957029b3151ba | null | 2004-01-01T00:10:00 | true | Cl.[OH:2][C:3]1[CH:13]=[CH:12][C:6]([C:7](=N)OCC)=[CH:5][CH:4]=1.[NH2:14][C:15]1[CH:16]=[C:17]([CH:20]=[CH:21][C:22]=1[NH:23][CH:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1)[C:18]#[N:19]>CO>[OH:2][C:3]1[CH:13]=[CH:12][C:6]([C:7]2[N:23]([CH:24]3[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29]3)[C:22]3[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][C:15]=3[N:14]=2)=[CH:5][CH:4]=1 | N#Cc1ccc(NC2CCCCC2)c(N)c1 | CCOC(=N)c1ccc(O)cc1 | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | 25 | null | A solution of ethyl 4-hydroxybenzimidate hydrochloride (5, 1.26 g, 6.7 mmol) and compound 4 (1.5 g, 5.0 mmol) in methanol (10 mL) was refluxed overnight under a nitrogen atmosphere. The reaction mixture was cooled to rt, filtered, and washed with methanol to afford 6 as a pinkish brown solid (1.26 g, 68%). ESI-MS m/e 372.1 (M+1). | N#Cc1ccc2c(c1)nc(-c1ccc(O)cc1)n2C1CCCCC1 | null | 79.4 | null |
54,976 | ord_dataset-159c363342e44b539e7a5975c873e30d | null | 1979-01-01T00:05:00 | true | Cl.[S:2]1[CH:6]=[CH:5][C:4]2[CH:7]([NH2:12])[CH2:8][CH2:9][CH2:10][CH2:11][C:3]1=2.[O-:13][C:14]#[N:15].[K+]>O>[S:2]1[CH:6]=[CH:5][C:4]2[CH:7]([NH:12][C:14]([NH2:15])=[O:13])[CH2:8][CH2:9][CH2:10][CH2:11][C:3]1=2 | NC1CCCCc2sccc21 | N#C[O-] | null | Cl | [K+] | 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 | 1 | A mixture of 50 grams of 5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophen-4-amine hydrochloride in 100 ml. of water is stirred at about 15° C. and a solution of 23.1 grams of potassium cyanate in 100 ml. of water is added dropwise. After completion of the addition, the mixture is warmed slowly to 70°-75° C. and held there for one hour. The mixture is cooled and the white solid is collected by filtration and washed with water. The solid is air-dried, pulverized, and washed with acetonitrile. Upon drying, this crude product is treated with hot acetone whereby there is obtained 5,6,7,8-tetrahydro-4H-cyclohepta[b]thien-4-ylurea, m.p. 217° C. dec. | NC(=O)NC1CCCCc2sccc21 | null | null | null |
136,829 | ord_dataset-a1d4c9f5edd844798727d514977ca73e | null | 1985-01-01T00:11:00 | true | Br[C:2]1[C:3]2[CH:11]=[CH:10][C:9]([CH2:12][CH2:13][OH:14])=[CH:8][C:4]=2[S:5][C:6]=1[CH3:7].C([Li])CCC.[C:20](=[O:22])=[O:21].C1(C)C=CC=CC=1>CCOCC>[OH:14][CH2:13][CH2:12][C:9]1[CH:10]=[CH:11][C:3]2[C:2]([C:20]([OH:22])=[O:21])=[C:6]([CH3:7])[S:5][C:4]=2[CH:8]=1 | Cc1sc2cc(CCO)ccc2c1Br | O=C=O | null | [Li]CCCC | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Cc1ccccc1 | CCOCC | null | null | null | null | null | null | null | null | null | null | null | Successive treatment of 3-bromo-6-(2-hydroxyethyl)-2-methylbenzo[b]thiophene with n-butyl lithium in ether followed by carbon dioxide according to the method of Example 11(ii) gave 6-(2-hydroxyethyl)-2-methylbenzo[b]thiophene-3-carboxylic acid, m.p. 166°-169° C. (from toluene). | Cc1sc2cc(CCO)ccc2c1C(=O)O | null | null | null |
409,484 | ord_dataset-324fb6fdc2414cb79e436bf5d04d4bd2 | null | 1998-01-01T00:08:00 | true | [OH:1][C:2]1[CH:3]=[C:4]([O:15][S:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[Cl:25])(=[O:18])=[O:17])[CH:5]=[CH:6][C:7]=1[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[C:26]([O:30][C:31]([N:33]1[CH2:38][CH2:37][CH:36]([CH2:39]O)[CH2:35][CH2:34]1)=[O:32])([CH3:29])([CH3:28])[CH3:27].CN1CCOCC1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[C:26]([O:30][C:31]([N:33]1[CH2:38][CH2:37][CH:36]([CH2:39][O:1][C:2]2[CH:3]=[C:4]([O:15][S:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[Cl:25])(=[O:18])=[O:17])[CH:5]=[CH:6][C:7]=2[CH2:8][C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:35][CH2:34]1)=[O:32])([CH3:29])([CH3:27])[CH3:28] | CC(C)(C)OC(=O)N1CCC(CO)CC1 | O=S(=O)(Oc1ccc(Cc2ccccc2)c(O)c1)c1ccccc1Cl | null | CCOC(=O)N=NC(=O)OCC | c1ccc(P(c2ccccc2)c2ccccc2)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN1CCOCC1 | C1CCOC1 | null | null | null | null | null | null | null | null | null | 25 | 1 | To 294 mg (0.787 mmol) of 2-chlorobenzenesulfonic acid 3-hydroxy-4-benzylphenyl ester, as prepared in the preceding step, in tetrahydrofuran (5 mL) containing 236 μL (1.10 mmol) of N-tert-butoxycarbonyl-4-piperidinemethanol, as prepared in step f of Example 1, 300 μL (2.72 mmol) of N-methylmorpholine, and 309 mg (1.18 mmol) of triphenylphosphine was added 185 μL (1.18 mmol) of diethyl azodicarboxylate. The reaction mixture was stirred at ambient temperature for 1 h, quenched with saturated NaHCO3, and extracted into ether. The organic phase was dried (MgSO4) and concentrated in vacuo. Purification by flash chromatography (ethyl acetate/hexane (1:2)) gave 382 mg of the title compound as a colorless foam. 1H-NMR (300 MHz, CDCl3) δ 7.95 (dd, 1H, J=1.5, 8 Hz), 7.55-7.64 (m, 2H), 7.35-7.40 (m, 1H), 7.08-7.26 (m, 5H), 6.93 (d, 2H, J=8 Hz), 6.65 (d, 2 Hz), 6.53 (dd, 1H, J=2, 8 Hz), 3.87 (s, 2H), 3.67 (d, 2H, 6 Hz), 2.69 (t, 2H, J=13 Hz), and 1.47 (s, 9H). Mass spectrum (MALDI-TOF; gentisic acid matrix) calcd. for C30H34ClNO6S: 594.2 (M+Na). Found: 594.0, 472.0 (M - (tert-butoxycarbonyl)+H). | CC(C)(C)OC(=O)N1CCC(COc2cc(OS(=O)(=O)c3ccccc3Cl)ccc2Cc2ccccc2)CC1 | null | 84.8 | null |
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