original_index int64 2 1.77M | extracted_from_file stringclasses 489 values | date_of_experiment timestamp[ns]date | grant_date timestamp[ns]date 1976-01-01 00:01:00 2016-01-01 00:09:00 | is_mapped bool 1 class | rxn_str stringlengths 87 6.12k | reactant_000 stringlengths 1 902 | reactant_001 stringlengths 1 902 ⌀ | reactant_002 null | agent_000 stringlengths 1 540 ⌀ | agent_001 stringlengths 1 852 ⌀ | agent_002 stringlengths 1 247 ⌀ | agent_003 null | agent_004 null | agent_005 null | agent_006 null | agent_007 null | agent_008 null | agent_009 null | agent_010 null | agent_011 null | agent_012 null | agent_013 null | agent_014 null | agent_015 null | agent_016 null | solvent_000 stringclasses 446 values | solvent_001 stringclasses 405 values | solvent_002 null | solvent_003 null | solvent_004 null | solvent_005 null | solvent_006 null | solvent_007 null | solvent_008 null | solvent_009 null | solvent_010 null | temperature float64 -230 30.1k ⌀ | rxn_time float64 0 2.16k ⌀ | procedure_details stringlengths 8 24.5k | product_000 stringlengths 1 484 | product_001 null | yield_000 float64 0 90,205,156,600B ⌀ | yield_001 float64 0 100M ⌀ |
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513,503 | ord_dataset-85c00026681b46f89ef8634d2b8618c3 | null | 2001-01-01T00:07:00 | true | [CH3:1][N:2]([CH3:23])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[CH:11][C:12]3[O:18][CH2:17][CH2:16][C:15]([C:19](O)=[O:20])=[CH:14][C:13]=3[CH:22]=2)=[CH:5][CH:4]=1.[CH3:24][N:25]([CH2:32][C:33]1[CH:39]=[CH:38][C:36]([NH2:37])=[CH:35][CH:34]=1)[CH:26]1[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1.C(N(CC)CC)C.P(C#N)(OCC)(OCC)=O>CN(C)C=O>[CH3:1][N:2]([CH3:23])[C:3]1[CH:4]=[CH:5][C:6]([C:9]2[CH:10]=[CH:11][C:12]3[O:18][CH2:17][CH2:16][C:15]([C:19]([NH:37][C:36]4[CH:38]=[CH:39][C:33]([CH2:32][N:25]([CH:26]5[CH2:31][CH2:30][O:29][CH2:28][CH2:27]5)[CH3:24])=[CH:34][CH:35]=4)=[O:20])=[CH:14][C:13]=3[CH:22]=2)=[CH:7][CH:8]=1 | CN(C)c1ccc(-c2ccc3c(c2)C=C(C(=O)O)CCO3)cc1 | CN(Cc1ccc(N)cc1)C1CCOCC1 | null | CCOP(=O)(C#N)OCC | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | CCN(CC)CC | null | null | null | null | null | null | null | null | null | 25 | null | To a solution of 7-(4-dimethylaminophenyl)-2,3-dihydro-1-benzoxepine-4-carboxylic acid (0.15 g), 4-(N-methyl-N-(tetrahydropyran-4-yl)aminomethyl)aniline (0.11 g) and triethylamine (0.2 ml) in dimethylformamide (15 ml) was added diethyl cyano-phosphate (0.11 ml) under ice-cooling, and the mixture was stirred under nitrogen atmosphere at room temperature over night. The solvent was evaporated, and the residue was purified with silica gel column (methanol/ethyl acetate/triethylamine) to give crude crystals, which were recrystallized from ethyl acetate-hexane to give 7-(4-dimethylaminophenyl)-N-(4-((N-tetrahydropyran-4-yl-N-methylamino)methyl)phenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (Compound 149) (0.07 g) as pale brown crystals. | CN(C)c1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(CN(C)C4CCOCC4)cc2)CCO3)cc1 | null | 28.2 | null |
1,348,903 | ord_dataset-6034127657614f02860ed057b62b882e | null | 2013-01-01T00:10:00 | true | [CH3:1][O:2][C:3]1[C:8]2[CH2:9][CH2:10][CH:11]([NH:14][CH2:15][C:16]([F:19])([F:18])[F:17])[CH2:12][CH2:13][C:7]=2[CH:6]=[CH:5][C:4]=1[NH2:20].Cl[C:22]1[N:27]=[C:26]([NH:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[N:35]2[CH:39]=[CH:38][CH:37]=[N:36]2)[C:25]([Cl:40])=[CH:24][N:23]=1>>[Cl:40][C:25]1[C:26]([NH:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[N:35]2[CH:39]=[CH:38][CH:37]=[N:36]2)=[N:27][C:22]([NH:20][C:4]2[CH:5]=[CH:6][C:7]3[CH2:13][CH2:12][CH:11]([NH:14][CH2:15][C:16]([F:18])([F:17])[F:19])[CH2:10][CH2:9][C:8]=3[C:3]=2[O:2][CH3:1])=[N:23][CH:24]=1 | Clc1ncc(Cl)c(Nc2ccccc2-n2cccn2)n1 | COc1c(N)ccc2c1CCC(NCC(F)(F)F)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 an analogous procedure to Example 651, part c, 1-Methoxy-N*7*-(2,2,2-trifluoro-ethyl)-6,7,8,9-tetrahydro-5H-benzocycloheptene-2,7-diamine was combined with (2,5-dichloro-pyrimidin-4-yl)-(2-pyrazol-1-yl-phenyl)-amine to yield -Chloro-N*2*-[1-methoxy-7-(2,2,2-trifluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-N*4*-(2-pyrazol-1-yl-phenyl)-pyrimidine-2,4-diamine (60.59 mg, 63% yield) as a red glass. 1H-NMR (CDCl3) δ 10.17 (s, 1H), 8.52 (d, J=8.3 Hz, 1H), 8.05 (m, 2H), 7.82 (d, J=18.2 Hz, 2H), 7.41 (m, 3H), 7.21 (m, 1H), 6.82 (d, J=8.2 Hz, 1H), 6.69 (d, J=8.1 Hz, 1H), 6.51 (m, 2H), 3.71 (s, 3H), 3.23 (m, 3H), 2.87 (m, 1H), 2.62 (m, 2H), 2.45 (m, 1H), 2.09 (m, 2H), 1.29 (m, 2H). | COc1c(Nc2ncc(Cl)c(Nc3ccccc3-n3cccn3)n2)ccc2c1CCC(NCC(F)(F)F)CC2 | null | 63 | null |
943,052 | ord_dataset-ed680843f6d14f5c9901869b2a06b4a4 | null | 2010-01-01T00:03:00 | true | Cl[C:2]1[N:7]=[C:6]([S:8][CH3:9])[N:5]=[C:4]2[N:10]([C:15]3[C:20]([F:21])=[CH:19][CH:18]=[CH:17][C:16]=3[F:22])[C:11](=[O:14])[NH:12][CH2:13][C:3]=12.[CH3:23][C:24]1[CH:30]=[CH:29][C:27]([NH2:28])=[CH:26][C:25]=1B1OC(C)(C)C(C)(C)O1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O>[NH2:28][C:27]1[CH:26]=[CH:25][C:24]([CH3:23])=[C:30]([C:2]2[N:7]=[C:6]([S:8][CH3:9])[N:5]=[C:4]3[N:10]([C:15]4[C:20]([F:21])=[CH:19][CH:18]=[CH:17][C:16]=4[F:22])[C:11](=[O:14])[NH:12][CH2:13][C:3]=23)[CH:29]=1 | CSc1nc(Cl)c2c(n1)N(c1c(F)cccc1F)C(=O)NC2 | Cc1ccc(N)cc1B1OC(C)(C)C(C)(C)O1 | null | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | C1COCCO1 | null | null | null | null | null | null | null | null | null | 95 | null | To 5-chloro-1-(2,6-difluorophenyl)-7-(methylthio)-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one (0.342 g, 1 mmol) and 4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (0.256 g, 1.1 mmol) in dioxane (40 mL), was added a solution of K2CO3 (0.417 g, 3 mmol) in water (10 mL). Argon was vigorously bubbled through the mixture for 5 minutes and then tetrakis(triphenyl-phosphine)palladium(0) (0.078 g, 0.05 mmol) was added. The mixture was heated in a 95° C. oil bath for 17 hours. The solvent was pumped off in vacuo, and the residue partitioned between ethyl acetate and water. The phases separated and the organic phase washed with brine, dried over anhydrous Na2SO4, filtered and evaporated. The crude product was flash chromatographed on silica gel (20 grams) eluted with 0-10% MeOH/CH2Cl2 to give the title product as a white solid. mp 122-125° C. LC-MS m/z 414 (M+H)+, 1.58 min (ret. time). | CSc1nc(-c2cc(N)ccc2C)c2c(n1)N(c1c(F)cccc1F)C(=O)NC2 | null | null | null |
263,684 | ord_dataset-a7bd0db0684c464bb02ff6a36065fee3 | null | 1993-01-01T00:03:00 | true | [S:1](Cl)(=[O:4])(=[O:3])[NH2:2].[O:6]([CH2:13][CH:14]([OH:16])[CH3:15])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1>>[O:6]([CH2:13][CH:14]([O:16][S:1](=[O:4])(=[O:3])[NH2:2])[CH3:15])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1 | CC(O)COc1ccccc1 | NS(=O)(=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 | The title compound was prepared by procedures of Example 22 from sulfamoyl chloride and 3-phenoxy-2-propanol through the partitioning and final evaporation to give an oil as residue. The oil was purified by chromatography using a 4.5 cm×100 cm glass column packed with 500 g of silica gel and methylene chloride as eluting agent. Fractions containing the title compound were combined and the solvent was evaporated under reduced pressure to give a 37% yield of an oil which solidified on standing, mp 57°-60° C. | CC(COc1ccccc1)OS(N)(=O)=O | null | null | null |
1,719,999 | ord_dataset-36057d699ac5449e9c37eb99abf78b03 | null | 2016-01-01T00:05:00 | true | [NH2:1][CH:2]([C:5]1[CH:10]=[CH:9][C:8]([C:11]([F:14])([F:13])[F:12])=[CH:7][CH:6]=1)[CH2:3][OH:4].[N:15]([C:18]1[CH:23]=[CH:22][C:21]([C:24]2[N:28]=[CH:27][N:26]([C:29]3[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:31][CH:30]=3)[N:25]=2)=[CH:20][CH:19]=1)=[C:16]=[S:17]>>[OH:4][CH2:3][CH:2]([NH:1][C:16]([NH:15][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[N:28]=[CH:27][N:26]([C:29]3[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:36])[F:37])=[CH:31][CH:30]=3)[N:25]=2)=[CH:20][CH:19]=1)=[S:17])[C:5]1[CH:6]=[CH:7][C:8]([C:11]([F:12])([F:13])[F:14])=[CH:9][CH:10]=1 | NC(CO)c1ccc(C(F)(F)F)cc1 | FC(F)(F)c1ccc(-n2cnc(-c3ccc(N=C=S)cc3)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 | The title compound was prepared with 2-amino-2-(4-(trifluoromethyl)phenyl)ethanol and 3-(4-isothiocyanatophenyl)-1-(4-(trifluoromethyl)phenyl)-1H-1,2,4-triazole and isolated as a white solid (1.54 g, quantitative): 1H NMR (300 MHz, CDCl3) δ 8.09 (s, 1H), 7.66 (d, J=8.7 Hz, 2H), 7.43 (d, J=6.3 Hz, 1H), 7.30 (d, J=8.4 Hz, 2H), 7.20 (d, J=8.6 Hz, 2H), 7.02 (d, J=8.2 Hz, 2H), 6.88-6.69 (m, 4H), 6.61-6.50 (m, 2H), 5.27-5.07 (m, 1H), 3.48-3.40 (m, 1H), 3.40-3.24 (m, 1H); ESIMS m/z 552 ([M+H]+). | OCC(NC(=S)Nc1ccc(-c2ncn(-c3ccc(C(F)(F)F)cc3)n2)cc1)c1ccc(C(F)(F)F)cc1 | null | null | null |
887,484 | ord_dataset-d728a2f811c0424cbcdb5a84d02b93ae | null | 2009-01-01T00:06:00 | true | I[CH2:2][C@H:3]([CH3:16])[CH2:4][N:5]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[O:8][CH2:7][C:6]1=[O:15].[CH2:17]([CH:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1)[CH2:18][CH2:19][CH3:20]>CC#N>[CH2:17]([CH:21]1[CH2:26][CH2:25][N:24]([CH2:2][C@H:3]([CH3:16])[CH2:4][N:5]2[C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=3[O:8][CH2:7][C:6]2=[O:15])[CH2:23][CH2:22]1)[CH2:18][CH2:19][CH3:20] | C[C@@H](CI)CN1C(=O)COc2ccccc21 | CCCCC1CCNCC1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC#N | null | null | null | null | null | null | null | null | null | null | 60 | 72 | A 4 ml vial was charged with crude (R)-4-(3-iodo-2-methyl-propyl]-4H-benzo[1,4]oxazin-3-one (108LM46-43) (0.312 g) and 4-butyl-piperidine (0.210 g, 1.49 mmol) in dry MeCN (½ ml) and shaken at 60° C. for 3 days. The reaction mixture was quenched with water (1 ml), and the product extracted into EtOAc (2×1 ml). The combined organic layers were added a cation exchange column. The column was washed with MeOH (2 column volumes) then the product was eluded of the column using 8% ammonium hydroxide in MeOH (2 column volumes). The product was purified by flash CC (SiO2; MeOH/DCM 1:20) to give the title compound (108LM53-50) (0.193 g, 17% -3 steps). 1H NMR (CDCl3) δ 7.18 (d, J=7.8 Hz, 1H), 7.03-6.96 (m, 3H), 4.58 (ABq, J=14.3 Hz, J=33.9 Hz, CH2), 4.05-3.90 (m, 2H), 2.88 (bd, J=10.4 Hz, 1H), 2.71 (bd, J=10.4 Hz, 1H), 2.25-2.01 (m, 3H), 2.00-1.92 (m, 1H), 1.83-1.75 (m, 1H), 1.68-1.56 (m, 2H), 1.33-112 (m, 9H), 0.95-0.85 (m, 6H); 13C NMR (CDCl3) δ 164.9, 145.7, 128.9, 123.8, 122.7, 117.2, 115.8, 67.8, 64.2, 55.8, 54.4, 45.4, 36.6, 36.1, 33.0, 32.8, 29.3, 23.2, 17.1, 14.4; HPLC-MS (ammonium acetate) [M+H]+=345.3. | CCCCC1CCN(C[C@H](C)CN2C(=O)COc3ccccc32)CC1 | null | 59.5 | null |
563,410 | ord_dataset-7c28974b7fcf4c9c86d5f2a42ba328a2 | null | 2002-01-01T00:09:00 | true | [NH2:1][CH2:2][CH2:3][O:4][C:5]1[CH:28]=[CH:27][C:8]([NH:9][CH:10]2[CH2:15][CH2:14][N:13]([C:16]([NH:18][CH2:19][C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)=[O:17])[CH2:12][CH2:11]2)=[CH:7][CH:6]=1.C([Si]([O:46][C:47]1[CH:52]=[CH:51][C:50]([O:53][CH2:54][CH:55]2[CH2:57][O:56]2)=[CH:49][CH:48]=1)(C1C=CC=CC=1)C1C=CC=CC=1)(C)(C)C>C(Cl)(Cl)Cl.CO>[F:26][C:23]1[CH:22]=[CH:21][C:20]([CH2:19][NH:18][C:16]([N:13]2[CH2:14][CH2:15][CH:10]([NH:9][C:8]3[CH:7]=[CH:6][C:5]([O:4][CH2:3][CH2:2][NH:1][CH2:57][C@H:55]([OH:56])[CH2:54][O:53][C:50]4[CH:51]=[CH:52][C:47]([OH:46])=[CH:48][CH:49]=4)=[CH:28][CH:27]=3)[CH2:11][CH2:12]2)=[O:17])=[CH:25][CH:24]=1 | CC(C)(C)[Si](Oc1ccc(OCC2CO2)cc1)(c1ccccc1)c1ccccc1 | NCCOc1ccc(NC2CCN(C(=O)NCc3ccc(F)cc3)CC2)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | ClC(Cl)Cl | null | null | null | null | null | null | null | null | null | null | null | 4-[4-(2-Aminoethoxy)anilino]-N-(4-fluorobenzyl)-1-piperidinecarboxamide (0.63 g, 1.4 mmol) was reacted with tert-butyl-(4-oxiranylmethoxy-phenoxy)-diphenyl-silane (0.53 g, 1.3 mmol) according to Procedure G (eluant: 20:1 chloroform-methanol) to give the title compound (0.125 g, 0.15 mmol). | O=C(NCc1ccc(F)cc1)N1CCC(Nc2ccc(OCCNC[C@H](O)COc3ccc(O)cc3)cc2)CC1 | null | 11.5 | null |
1,721,319 | ord_dataset-36057d699ac5449e9c37eb99abf78b03 | null | 2016-01-01T00:05:00 | true | Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH3:11])=[N:9][N:10]=2)[N:7]=1.[CH3:12][NH:13][C@@H:14]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH3:15]>CN1C(=O)CCC1>[CH3:12][N:13]([C@@H:14]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH3:15])[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH3:11])=[N:9][N:10]=2)[N:7]=1 | CN[C@H](C)c1ccccc1 | Cc1nnc2ccc(Cl)nn12 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN1CCCC1=O | null | null | null | null | null | null | null | null | null | null | 200 | null | 6-Chloro-3-methyl-[1,2,4]triazolo[4,3-b]pyridazine (150 mg, 0.890 mmol; commercially available or prepared according to patent WO2006/039325A2), (R)-N-methyl-1-phenylethanamine (481 mg, 3.56 mmol; available from Aldrich) and anhydrous NMP (1 mL) were charged into a microwave tube equipped with a magnetic stirbar. After the vessel was sealed, the mixture was heated at 200° C. for 60 min using microwave irradiation. The reaction was purified by normal phase (gradient of 0% to 20% MeOH in CH2Cl2 as eluent) and by reverse phase chromatography before being lyophilized to give the (R)-N,3-dimethyl-N-(1-phenylethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-amine (Compound 3) as an off-white solid (115 mg; 48% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.01 (d, J=10.1 Hz, 1H), 7.23-7.41 (m, 6H), 5.71 (q, J=6.8 Hz, 1H), 2.83 (s, 3H), 2.54 (s, 3H), 1.58 (d, J=7.1 Hz, 3H). LRMS [M+H]+: 268 m/z. | Cc1nnc2ccc(N(C)[C@H](C)c3ccccc3)nn12 | null | null | null |
1,752,664 | ord_dataset-97eb2ab57fec4160922caae33b54d956 | null | 2016-01-01T00:08:00 | true | [O:1]1[CH2:5][CH2:4][CH2:3][C@H:2]1[C@H:6]([O:10][CH2:11][CH:12]=O)[CH2:7][CH:8]=[CH2:9].[OH:14][N:15]=CCOC([C@@H]1C[C@H]1C)CC=C>>[OH:14][N:15]=[CH:12][CH2:11][O:10][C@@H:6]([C@@H:2]1[CH2:3][CH2:4][CH2:5][O:1]1)[CH2:7][CH:8]=[CH2:9] | C=CCC(OCC=NO)[C@@H]1C[C@H]1C | C=CC[C@@H](OCC=O)[C@@H]1CCCO1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ({(1R)-1-[(2S)-Tetrahydrofuran-2-yl]but-3-en-1-yl}oxy)acetaldehyde (C97) was converted to the product using the method described for the synthesis of N-hydroxy-2-({1-[(1R,2R)-2-methylcyclopropyl]but-3-en-1-yl}oxy)ethanimine (C84) in Example 20. Yield: 4.7 g, 23.6 mmol, 65% over 2 steps from (C95). | C=CC[C@@H](OCC=NO)[C@@H]1CCCO1 | null | null | null |
1,105,417 | ord_dataset-375a420ee9b042918ddca20f02df37d3 | null | 2011-01-01T00:11:00 | true | [C:1]([O-:4])([O-])=[O:2].[K+].[K+].Br[C:8]1([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[CH:21]=2)[C:16]2[C:11](=[CH:12][C:13]([Cl:17])=[CH:14][CH:15]=2)[NH:10][C:9]1=[O:18]>O1CCOCC1>[Cl:17][C:13]1[CH:12]=[C:11]2[C:16]([C:8]([NH:10][CH:9]([CH2:8][CH:16]([CH3:11])[CH3:15])[C:1]([OH:4])=[O:2])([CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[CH:21]=3)[C:9](=[O:18])[NH:10]2)=[CH:15][CH:14]=1 | O=C1Nc2cc(Cl)ccc2C1(Br)Cc1cccc(Cl)c1 | O=C([O-])[O-] | null | [K+] | 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 | 25 | 4 | To the aqueous solution K2CO3 (1.6 μL, 1N) was added (2S)-amino-4-methyl-pentanoic (106 mg, 0.81 mmol), then followed by the addition of rac-3-bromo-6-chloro-3-(3-chloro-benzyl)-1,3-dihydro-indol-2-one (200 mg, 0.54 mmol) in dioxane (5 mL). After the mixture was stirred at room temperature for 4 h, the reaction mixture was concentrated in vacuo. Water (10 mL) was added and the crude was acidified with HCl to PH=4. The mixture was extracted with ethyl acetate (3×10 mL). The combined organic layer was concentrated in vacuo. The residue was purified by chromatography (DCM: MeOH=80:1) to give 184 mg of rac-(2S)-[6-chloro-3-(3-chloro-benzyl)-2-oxo-2,3-dihydro-1H-indol-3-ylamino]-4-methyl-pentanoic acid as a white solid. MS: 421 (M+H)+. H1-NMR (400 MHz, CDCl3) δ 10.04 (s, 1H), 7.12 (m, 5H), 6.93 (t, 1H), 6.76 (m, 2H), 3.32 (m, 1H), 3.16 (dd, 2H), 1.89 (m, 1H), 1.50 (m, 2H), 0.90 (dd, 6H). | CC(C)CC(NC1(Cc2cccc(Cl)c2)C(=O)Nc2cc(Cl)ccc21)C(=O)O | null | null | null |
1,737,765 | ord_dataset-eacfee6d16d8455a93348409f1b37be4 | null | 2016-01-01T00:06:00 | true | Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]3[C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[CH:14]=[CH:13][CH:12]=3)=[CH:9][N:10]=2)[N:7]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[NH2:33][CH2:34][CH2:35][CH2:36][CH2:37][OH:38]>CS(C)=O.O>[C:11]1([C:8]2[N:6]3[N:7]=[C:2]([NH:33][CH2:34][CH2:35][CH2:36][CH2:37][OH:38])[CH:3]=[CH:4][C:5]3=[N:10][CH:9]=2)[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[CH:13][CH:12]=1 | NCCCCO | Clc1ccc2ncc(-c3cccc4ccccc34)n2n1 | null | Cc1ccc(S(=O)(=O)O)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CS(C)=O | null | null | null | null | null | null | null | null | null | 100 | null | To a solution of 6-chloro-3-(naphthalen-1-yl)imidazo[1,2-b]pyridazine (50 mg, 0.179 mmol, 1.0 equiv) in DMSO (2.0 mL) was added p-toluene sulfonic acid monohydrate (35 mg, 0.184 mmol, 1.0 equiv) and 4-aminobutan-1-ol (200 mg, 2.24 mmol, 12.5 equiv) and heated to 100° C. for 24 h. The reaction mixture was diluted with water and extracted with ethyl acetate. Purification by column chromatography using 5% methanol in dichloromethane elution gave 30 mg of a white solid, 50%. | OCCCCNc1ccc2ncc(-c3cccc4ccccc34)n2n1 | null | 50.4 | null |
1,080,183 | ord_dataset-afd812677c134591a99f46ce28de2524 | null | 2011-01-01T00:08:00 | true | FC(F)(F)C(O)=O.[C:8]([NH:16][C:17]1[CH:29]=[C:28]([CH2:30][CH2:31][CH2:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH:27]=[CH:26][C:18]=1[C:19]([O:21]C(C)(C)C)=[O:20])(=[O:15])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>>[C:8]([NH:16][C:17]1[CH:29]=[C:28]([CH2:30][CH2:31][CH2:32][CH2:33][C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH:27]=[CH:26][C:18]=1[C:19]([OH:21])=[O:20])(=[O:15])[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1 | CC(C)(C)OC(=O)c1ccc(CCCCc2ccccc2)cc1NC(=O)c1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O=C(O)C(F)(F)F | null | null | null | null | null | null | null | null | null | null | null | null | 4.9 mL solution of trifluoroacetic acid containing 0.50 g of tert-butyl 2-(benzamido)-4-(4-phenylbutyl)benzoate was stirred at room temperature for 2 hours and 30 minutes. A solid substance was separated by filtration to obtain 0.16 g of 2-(benzamido)-4-(4-phenylbutyl)benzoic acid as white solid. | O=C(Nc1cc(CCCCc2ccccc2)ccc1C(=O)O)c1ccccc1 | null | null | null |
1,413,267 | ord_dataset-f8e6e6a2d2bf4135b9e346456c81700f | null | 2014-01-01T00:04:00 | true | [Na].[Br:2][C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][CH:4]=1.[CH:10]12[O:16][CH:15]1[CH2:14][CH2:13][CH2:12][CH2:11]2>C(O)C>[Br:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][C@@H:14]2[CH2:13][CH2:12][CH2:11][CH2:10][C@H:15]2[OH:16])=[CH:5][CH:4]=1 | C1CCC2OC2C1 | Oc1ccc(Br)cc1 | null | [Na] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | null | null | null | null | null | null | null | null | null | null | null | null | Sodium metal (2.58 g, 112 mmol) was combined with absolute ethanol (200 mL) and allowed to react completely. 4-Bromophenol (19.4 g, 112 mmol) was added, and the reaction was stirred for 20 minutes, at which point 7-oxabicyclo[4.1.0]heptane (10.0 g, 102 mmol) was added, and the solution was heated at reflux for 15 hours. After removal of solvent in vacuo, the residue was partitioned between water (300 mL) and ethyl acetate (100 mL). The aqueous layer was extracted with ethyl acetate (2×100 mL), and the combined organic layers were washed with water (2×200 mL), dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting light tan solid was recrystallized from heptane (roughly 200 mL) to provide trans-2-(4-bromophenoxy)cyclohexanol as a fluffy white solid. Yield: 12.5 g, 46.1 mmol, 45%. 1H NMR (400 MHz, CDCl3) δ 1.26-1.46 (m, 4H), 1.75-1.79 (m, 2H), 2.08-2.14 (m, 2H), 2.52 (d, J=2.1 Hz, 1H), 3.72 (m, 1H), 3.96 (ddd, J=10.3, 8.6, 4.4 Hz, 1H), 6.84 (d, J=9.0 Hz, 2H), 7.37 (d, J=9.0 Hz, 2H). | O[C@@H]1CCCC[C@H]1Oc1ccc(Br)cc1 | null | null | null |
645,406 | ord_dataset-c975a50a7600448fabd558f4a94a3e29 | null | 2004-01-01T00:08:00 | true | [C:1]1([S:7]([N:10]2[C:22]3[CH:21]=[CH:20][CH:19]=[C:18]([O:23][CH2:24][CH:25]4[CH2:27][O:26]4)[C:17]=3[C:16]3[C:11]2=[CH:12][CH:13]=[CH:14][CH:15]=3)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:28][O:29][C:30]1[CH:39]=[CH:38][CH:37]=[CH:36][C:31]=1[O:32][CH2:33][CH2:34][NH2:35]>>[C:1]1([S:7]([N:10]2[C:22]3[CH:21]=[CH:20][CH:19]=[C:18]([O:23][CH2:24][CH:25]([OH:26])[CH2:27][N:35]([CH2:17][C:16]4[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=4)[CH2:34][CH2:33][O:32][C:31]4[CH:36]=[CH:37][CH:38]=[CH:39][C:30]=4[O:29][CH3:28])[C:17]=3[C:16]3[C:11]2=[CH:12][CH:13]=[CH:14][CH:15]=3)(=[O:8])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1 | COc1ccccc1OCCN | O=S(=O)(c1ccccc1)n1c2ccccc2c2c(OCC3CO3)cccc21 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | reaction of 9-benzenesulfonyl-4-oxiranylmethoxy-9H-carbazole with benzyl-[2-(2-methoxy-phenoxy]-ethyl-amine to give a 1-(9-benzenesulfonyl-9H-carbazol-4-yloxy)-3-{benzyl-[2-(2-methoxy-phenoxy)ethyl]-amino}-propan-2-ol; | COc1ccccc1OCCN(Cc1ccccc1)CC(O)COc1cccc2c1c1ccccc1n2S(=O)(=O)c1ccccc1 | null | null | null |
850,368 | ord_dataset-171b840ae6e84e45bab43b987d09f5c7 | null | 2008-01-01T00:11:00 | true | Br[C:2]1[C:3]([O:10][CH3:11])=[N:4][CH:5]=[N:6][C:7]=1[O:8][CH3:9].[N:12]1[CH:17]=[CH:16][C:15](B(O)O)=[CH:14][CH:13]=1.C([O-])([O-])=O.[K+].[K+]>C(O)C.C1COCC1>[CH3:11][O:10][C:3]1[C:2]([C:15]2[CH:16]=[CH:17][N:12]=[CH:13][CH:14]=2)=[C:7]([O:8][CH3:9])[N:6]=[CH:5][N:4]=1 | COc1ncnc(OC)c1Br | OB(O)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 | 70 | null | A mixture of 5-bromo-4,6-dimethoxypyrimidine (2.18 g, 10 mmol), pyridine-4-boronic acid (1.85 g, 15 mmol), K2CO3 (2.76 g, 20 mmol), and PXPd (539 mg, 1.0 mmol) in ethanol/THF (1:1, 25 mL) under argon was heated at 70° C. for 3 h. Analysis by HPLC/MS indicated that the reaction was complete. After the reaction mixture was cooled to room temperature, the solvent mixture was removed under reduced pressure. The residue was dissolved in EtOAc (30 mL) and washed with saturated aqueous NaCl (20 mL), then dried over Na2SO4, filtered and evaporated under reduced pressure. The crude product was purified by silica gel column chromatography eluted with ethyl acetate-hexanes to obtain the title compound (1.79 g) as a white solid. 1H NMR (CDCl3): δ 3.97 (s, 6H), 7.36 (d, 2H), 8.47 (s, 1H), 8.64 (d, 2H). | COc1ncnc(OC)c1-c1ccncc1 | null | 82.4 | null |
1,069,933 | ord_dataset-5df93261afc143c3ae919a57ff4fc1d4 | null | 2011-01-01T00:07:00 | true | FC(F)(F)C(O)=O.[CH2:8]([O:12][C:13]1[NH:14][C:15]([NH2:24])=[C:16]2[C:20]([N:21]=1)=[N:19][C:18]([O:22][CH3:23])=[N:17]2)[CH2:9][CH2:10][CH3:11].Br[CH2:26][CH2:27][C@@H:28]1[CH2:32][CH2:31][O:30][CH2:29]1>>[CH2:8]([O:12][C:13]1[N:21]=[C:20]2[C:16]([N:17]=[C:18]([O:22][CH3:23])[N:19]2[CH2:26][CH2:27][C@@H:28]2[CH2:32][CH2:31][O:30][CH2:29]2)=[C:15]([NH2:24])[N:14]=1)[CH2:9][CH2:10][CH3:11] | BrCC[C@@H]1CCOC1 | CCCCOc1nc2nc(OC)nc-2c(N)[nH]1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O=C(O)C(F)(F)F | null | null | null | null | null | null | null | null | null | null | null | null | Prepared similarly to Intermediate 215 from 2-(butyloxy)-8-(methyloxy)-1H-purin-6-amine trifluoroacetate and (3S)-3-(2-bromoethyl)tetrahydrofuran. | CCCCOc1nc(N)c2nc(OC)n(CC[C@@H]3CCOC3)c2n1 | null | null | null |
1,174,713 | ord_dataset-0f9d2dbe929a45c3892ae75e81e99443 | null | 2012-01-01T00:06:00 | true | [CH2:1]([C:8]1([C:21](=[O:35])[NH:22][C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([O:29][C:30](=[O:34])[N:31]([CH3:33])[CH3:32])[CH:24]=2)[CH2:13][CH2:12][N:11](C(OC(C)(C)C)=O)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.O1CCOCC1>CO>[CH3:33][N:31]([CH3:32])[C:30](=[O:34])[O:29][C:25]1[CH:26]=[CH:27][CH:28]=[C:23]([NH:22][C:21]([C:8]2([CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH2:9][CH2:10][NH:11][CH2:12][CH2:13]2)=[O:35])[CH:24]=1 | CN(C)C(=O)Oc1cccc(NC(=O)C2(Cc3ccccc3)CCN(C(=O)OC(C)(C)C)CC2)c1 | null | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | C1COCCO1 | null | null | null | null | null | null | null | null | null | 50 | null | To a solution of tert-butyl 4-benzyl-4-(3-(dimethylcarbamoyloxy)-phenylcarbamoyl)piperidine-1-carboxylate from step A (0.162 g, 0.336 mmol) in MeOH (5 mL) was added 4 M HCl in dioxane (0.250 mL, 1.00 mmol). The reaction was heated at 50° C. for 1 hour, and then concentrated under vacuum, re-dissolved in MeOH and re-concentrated twice to give the title compound as the hydrochloride salt. MS (ES+) [M+H]+=382. | CN(C)C(=O)Oc1cccc(NC(=O)C2(Cc3ccccc3)CCNCC2)c1 | null | null | null |
252,281 | ord_dataset-49bd993346b64eeeb2a8fe2643164a0a | null | 1992-01-01T00:08:00 | true | [Cl:1][C:2]1[CH:13]=[C:12]([Cl:14])[C:11]([N:15]2[C:19](=[O:20])[N:18]([CH2:21][CH2:22][CH3:23])[N:17]=[N:16]2)=[CH:10][C:3]=1[O:4][CH2:5][C:6]([O:8]C)=[O:7].[OH-].[Na+].Cl>CO.O>[Cl:1][C:2]1[CH:13]=[C:12]([Cl:14])[C:11]([N:15]2[C:19](=[O:20])[N:18]([CH2:21][CH2:22][CH3:23])[N:17]=[N:16]2)=[CH:10][C:3]=1[O:4][CH2:5][C:6]([OH:8])=[O:7] | CCCn1nnn(-c2cc(OCC(=O)OC)c(Cl)cc2Cl)c1=O | null | null | Cl | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CO | null | null | null | null | null | null | null | null | null | null | null | A stirred solution of 0.5 g (0.0014 mole) of methyl 2,4-dichloro-5-(1,4-dihydro-5-oxo-4-propyltetrazol-1-yl)phenoxyacetate (compound 83) and 0.08 g (0.0021 mole) of sodium hydroxide in 10 mL of methanol was heated at reflux temperature for 1.5 hours. The reaction mixture was cooled, then evaporated under reduced pressure to leave a solid residue. The residue was dissolved in 20 mL of water, and the solution acidified with concentrated hydrochloric acid. A solid precipitate formed and was collected by filtration and washed with cold water. Recrystallization from diethyl ether:pentane provided 0.2 g of 2,4-dichloro-5-[1,4-dihydro-5-oxo-4-propyltetrazol-1-yl)phenoxyacetic acid, mp 134°-136° C. | CCCn1nnn(-c2cc(OCC(=O)O)c(Cl)cc2Cl)c1=O | null | 41.2 | null |
1,494,799 | ord_dataset-366bdd9ee72d474cbe6f3f9e54dd96d2 | null | 2014-01-01T00:10:00 | true | Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]([N:10]([CH3:33])[C:11]2[CH:16]=[CH:15][C:14]([CH2:17][N:18]3[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C@@H:20]([CH3:31])[CH2:19]3)=[C:13]([F:32])[CH:12]=2)=[O:9])=[CH:4][CH:3]=1.[F:34][C:35]1[CH:40]=[CH:39][C:38]([OH:41])=[CH:37][CH:36]=1>>[F:32][C:13]1[CH:12]=[C:11]([N:10]([C:8]([C:5]2[CH:6]=[N:7][C:2]([O:41][C:38]3[CH:39]=[CH:40][C:35]([F:34])=[CH:36][CH:37]=3)=[CH:3][CH:4]=2)=[O:9])[CH3:33])[CH:16]=[CH:15][C:14]=1[CH2:17][N:18]1[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C@@H:20]([CH3:31])[CH2:19]1 | Oc1ccc(F)cc1 | C[C@H]1CN(Cc2ccc(N(C)C(=O)c3ccc(Cl)nc3)cc2F)CCN1C(=O)OC(C)(C)C | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | 8 | The title compound was prepared from 1,1-dimethylethyl (2S)-4-({4-[[(6-chloro-3-pyridinyl)carbonyl](methyl)amino]-2-fluorophenyl}methyl)-2-methyl-1-piperazinecarboxylate (D70) and 4-fluorophenol using a method similar to that described for D55 in Description 55 although the reaction temp./time was 130° C. for 8 h and purification was carried out by column chromatography. δH (CDCl3, 400 MHz) 8.07 (1H, dd), 7.70 (1H, dd), 7.33 (1H, t), 7.05 (4H, m), 6.78 (3H, m), 4.19 (1H, br.s), 3.81 (1H, d), 3.47 (5H, m), 3.07 (1H, td), 2.71 (1H, d), 2.53 (1H, d), 2.18 (1H, dd), 2.04 (1H, m), 1.46 (9H, s), 1.20 (3H, d). | C[C@H]1CN(Cc2ccc(N(C)C(=O)c3ccc(Oc4ccc(F)cc4)nc3)cc2F)CCN1C(=O)OC(C)(C)C | null | null | null |
582,199 | ord_dataset-60f3171f0342452f8814e7f294e2be8b | null | 2003-01-01T00:02:00 | true | [O-:1][CH2:2][CH3:3].[Na+].F[C:6]1[CH:11]=[CH:10][N:9]=[CH:8][C:7]=1[O:12][CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18].O>C(O)C>[CH2:2]([O:1][C:6]1[CH:11]=[CH:10][N:9]=[CH:8][C:7]=1[O:12][CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[CH3:3] | C[Si](C)(C)CCOCOc1cnccc1F | CC[O-] | null | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | O | null | null | null | null | null | null | null | null | null | 25 | 48 | To a stirred solution of sodium ethoxide (0.9 g, 13 mmol) in ethanol (10 mL) was added all at once 10 (1.07 g, 4.4 mmol). The resulting mixture was stirred at room temperature for 48 hours, then poured into water (100 mL). The resulting mixture was extracted with ether (3×50 mL). The ether extracts were combined, dried (MgSO4) and concentrated. The resulting amber oil was chromatographed (silica gel, hexane-acetone, 4:1) to give 11 as a yellow oil (0.6 g). | CCOc1ccncc1OCOCC[Si](C)(C)C | null | 50.6 | null |
27,833 | ord_dataset-14866e68bb5b47f5929457eecb4eb3a5 | null | 1977-01-01T00:07:00 | true | [CH3:1][C:2]1[N+:11]([O-:12])=[C:10]2[C:5]([CH:6]=[CH:7][CH:8]=[CH:9]2)=[N+:4]([O-:13])[C:3]=1[C:14]([O:16][CH3:17])=[O:15].[Br:18]Br.CO>CN(C)C=O>[Br:18][CH2:1][C:2]1[N+:11]([O-:12])=[C:10]2[C:5]([CH:6]=[CH:7][CH:8]=[CH:9]2)=[N+:4]([O-:13])[C:3]=1[C:14]([O:16][CH3:17])=[O:15] | BrBr | COC(=O)c1c(C)[n+]([O-])c2ccccc2[n+]1[O-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | 1.5 | Methyl 3-methyl-2-quinoxalinecarboxylate-1,4-dioxide (1.2 moles) were suspended in 475 ml of dimethylformamide and 64 ml of bromine was added dropwise with stirring over 1.5 hours while the temperature rose to 42° C. After additional stirring for 48 hours 1.5 liters of methanol were added and stirred for about 1/2 hour. The precipitated product was removed by filtration, washed with water and dried. Yield, 251 grams (68%); m.p. 113°-16° C. | COC(=O)c1c(CBr)[n+]([O-])c2ccccc2[n+]1[O-] | null | null | null |
1,299,681 | ord_dataset-de51ecc8d4434bacaa8bc32d7d73484c | null | 2013-01-01T00:05:00 | true | [O:1]=[C:2]1[NH:7][C:6]2[CH:8]=[C:9]([CH2:12][N:13]3[CH2:18][CH2:17][N:16]([C:19]4[CH:27]=[CH:26][C:22]([C:23](O)=[O:24])=[CH:21][CH:20]=4)[CH2:15][CH2:14]3)[CH:10]=[N:11][C:5]=2[N:4]2[CH2:28][CH2:29][CH2:30][C@@H:3]12.[CH3:31][CH2:32][N:33](C(C)C)C(C)C.C(N)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH2:32]([NH:33][C:23](=[O:24])[C:22]1[CH:26]=[CH:27][C:19]([N:16]2[CH2:15][CH2:14][N:13]([CH2:12][C:9]3[CH:10]=[N:11][C:5]4[N:4]5[CH2:28][CH2:29][CH2:30][C@H:3]5[C:2](=[O:1])[NH:7][C:6]=4[CH:8]=3)[CH2:18][CH2:17]2)=[CH:20][CH:21]=1)[CH3:31] | O=C(O)c1ccc(N2CCN(Cc3cnc4c(c3)NC(=O)[C@@H]3CCCN43)CC2)cc1 | CCN(C(C)C)C(C)C | null | CCN | CN(C)C(On1nnc2cccnc21)=[N+](C)C | F[P-](F)(F)(F)(F)F | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | 25 | 2 | (S)-4-(4-((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)benzoic acid (75.0 mg, 0.184 mmol) was suspended in DMF (1.0 mL) and DIPEA (0.15 mL) was added followed by ethylamine (30 mg, 0.665 mmol) and HATU (85.0 mg, 0.224 mmol). The reaction mixture was stirred at ambient temperature for 2 h and another portion of HATU (60.0 mg, 0.158 mmol) was added. The reaction mixture was stirred overnight and purified using HPCL (10-75% acetonitrile in water, NH4HCO3 buffered). The fractions were concentrated in vacuo and the resulting residue was crystallized with MeOH-water (1:10, 5 mL) to afford the title compound as a light green solid (24.0 mg, 30%). 1H NMR (400 MHz, DMSO-d6) δ (ppm): 1.09 (t, J=7.20 Hz, 3 H) 1.85-2.01 (m, 3 H) 2.18 (dt, J=5.37, 2.75 Hz, 1 H) 2.43-2.48 (m, 4 H) 3.18-3.28 (m, 6 H) 3.35 (s, 2 H) 3.37-3.45 (m, 1 H) 3.54-3.67 (m, 1 H) 3.94-4.05 (m, 1 H) 6.92 (d, J=9.09 Hz, 2 H) 6.99 (d, J=2.02 Hz, 1 H) 7.62 (d, J=2.02 Hz, 1 H) 7.71 (d, J=9.09 Hz, 2 H) 8.17 (t, J=5.56 Hz, 1 H) 10.44 (s, 1 H); [M+H] calc'd for C24H30N6O2, 435; found, 435. | CCNC(=O)c1ccc(N2CCN(Cc3cnc4c(c3)NC(=O)[C@@H]3CCCN43)CC2)cc1 | null | 30 | null |
1,648,120 | ord_dataset-bcc0b01d4f58457a8733b10a099f43ba | null | 2015-01-01T00:10:00 | true | [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].C([O-])([O-])=O.[K+].[K+].[Br:18][CH2:19][CH2:20][CH2:21]Br>CN(C=O)C.O>[Br:18][CH2:19][CH2:20][CH2:21][O:8][C:5]1[CH:6]=[CH:7][C:2]([CH3:1])=[C:3]([N+:9]([O-:11])=[O:10])[CH:4]=1 | Cc1ccc(O)cc1[N+](=O)[O-] | BrCCCBr | null | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | O | null | null | null | null | null | null | null | null | null | 100 | null | A solution of 4-methyl-3-nitrophenol (1.00 g, 6.53 mmol) in DMF (6 mL) was treated with K2CO3 (0.903 g, 6.53 mmol) and 1,3-dibromopropane (6.63 mL, 65.3 mmol) and heated to 100° C. for 2.5 h. The cooled mixture was diluted with water and extracted with DCM. The combined organics were dried (MgSO4), filtered and evaporated before purification by column chromatography (SiO2; eluting with 20% EtOAc in cyclohexane) to afford the desired product V-h as a mobile yellow oil (1.05 g, 59%). 1H NMR (300 MHz, CDCl3) δ 7.52 (d, J=2.7 Hz, 1H), 7.23 (d, J=8.5 Hz, 1H), 7.06 (dd, J=8.5, 2.7 Hz, 1H), 4.14 (t, J=5.8 Hz, 2H), 3.60 (t, J=6.4 Hz, 2H), 2.53 (s, 3H), 2.40-2.24 (m, 2H). | Cc1ccc(OCCCBr)cc1[N+](=O)[O-] | null | null | null |
688,798 | ord_dataset-56747de2718a4ac5bf061651d1cc9e3e | null | 2005-01-01T00:10:00 | true | [NH:1]1[CH:5]=[C:4]([CH:6]=[O:7])[N:3]=[CH:2]1.[H-].[Na+].[CH:10]1([CH2:16][CH2:17]Br)[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1>O1CCCC1>[CH:10]1([CH2:16][CH2:17][N:1]2[CH:5]=[C:4]([CH:6]=[O:7])[N:3]=[CH:2]2)[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1 | O=Cc1c[nH]cn1 | BrCCC1CCCCC1 | 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 | 1 | Imidazole-4-carboxaldehyde (4.8 g, 50 mmol) was added portionwise to a suspension of sodium hydride (2.20 g, 60% dispersion in mineral oil, 55 mmol) in tetrahydrofuran (150 ml), and the mixture was then stirred at room temperature for 1 hour. 2-Cyclohexylethyl bromide (8.6 ml, 55 mmol) was added, and the mixture was heated under reflux for 18 hours. The cooled mixture was evaporated under reduced pressure and the residue was partitioned between water (500 ml) and dichlorornethane (500 ml). The layers were separated, and the organic phase was dried (MgSO4) and evaporated under reduced pressure. The crude product was purified by column chromatography on silica gel using an elution gradient of toluene:ethyl acetate (100:0 to 96:4) to afford the title compound, 1.78 g. 1H-NMR (CDCl3, 400 MHz) δ: 0.98 (m, 2H), 1.20 (m, 4H), 1.68 (m, 7H), 4.00 (t, 2H), 7.4 (s, 1H), 7.60 (s, 1H), 9.80 (s, 1H). LRMS: m/z (TSP+) 207.2 [MH+]. | O=Cc1cn(CCC2CCCCC2)cn1 | null | null | null |
1,324,817 | ord_dataset-cfad8b3f00044bcda60a96b019f09872 | null | 2013-01-01T00:08:00 | true | Br[C:2]1[N:7]2[N:8]=[C:9]([NH2:11])[N:10]=[C:6]2[CH:5]=[CH:4][CH:3]=1.[CH3:12][S:13]([NH:16][C:17]1[CH:18]=[C:19](B(O)O)[CH:20]=[CH:21][CH:22]=1)(=[O:15])=[O:14]>>[NH2:11][C:9]1[N:10]=[C:6]2[CH:5]=[CH:4][CH:3]=[C:2]([C:21]3[CH:22]=[C:17]([NH:16][S:13]([CH3:12])(=[O:14])=[O:15])[CH:18]=[CH:19][CH:20]=3)[N:7]2[N:8]=1 | Nc1nc2cccc(Br)n2n1 | CS(=O)(=O)Nc1cccc(B(O)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 | N-[3-(2-Amino-[1,2,4]triazolo[1,5-a]pyridin-5-yl)-phenyl]-methanesulfonamide was prepared from 5-bromo-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine (1.80 g, 8.45 mmol) and 3-methylsulfonylaminophenyl boronic acid (2.0 g, 9.30 mmol), in a manner analogous to Step 73c. The residue was purified on an 80 g Isco silica gel column using a gradient of 0-7% methanol in dichloromethane as an eluent. N-[3-(2-Amino-[1,2,4]triazolo[1,5-a]pyridin-5-yl)-phenyl]-methanesulfonamide (461 mg, 18%) was isolated as a beige powder. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 9.94 (s, 1H), 7.72 (s, 1H), 7.64 (d, J=7.5 Hz, 1H), 7.51 (m, 2H), 7.38 (d, J=8.6 Hz, 1H), 7.32 (d, J=7.5 Hz, 1H), 6.97 (d, J=7.5 Hz, 1H), 6.03 (br s, 2H), 3.08 (s, 3H). MS=304 (MH)+. 83b) 5 N-[3-(2-Amino-[1,2,4]triazolo[1,5-a]pyridin-5-yl)-phenyl]-methanesulfonamide (162 mg, 0.534 mmol) and 1-(4-bromo-phenyl)-4-methyl-piperazine (150 mg, 0.587 mmol) were combined in a manner analogous to Example 77 to yield N-(3-{2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-[1,2,4]triazolo[1,5-a]pyridin-5-yl}-phenyl)-methanesulfonamide TFA salt (13.75 mg, 5%) as a yellow powder following purification via preparative HPLC on a Phenomenex Luna column using 0.1% TFA in MeCN and 0.1% TFA in Water as eluent. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 9.99 (s, 1H), 9.41 (s, 1H), 7.81 (s, 1H), 7.74 (d, J=8.0 Hz, 1H), 7.64 (t, J=8.3 Hz, 1H), 7.50-7.61 (m, 3H), 7.08-7.42 (m, 3H), 6.93 (d, J=7.2 Hz, 2H), 3.67 (m, 2H), 3.18 (m, 4H), 3.07 (s, 3H), 2.86 (br s, 5H). MS=478 (MH)+. | CS(=O)(=O)Nc1cccc(-c2cccc3nc(N)nn23)c1 | null | 18 | null |
644,942 | ord_dataset-c975a50a7600448fabd558f4a94a3e29 | null | 2004-01-01T00:08:00 | true | [NH2:1][C:2]1[N:3]=[C:4](Cl)[C:5]2[CH:10]=[CH:9][N:8]([C@@H:11]3[O:17][C@H:16]([CH2:18][OH:19])[C@@H:14]([OH:15])[C@@:12]3([CH3:20])[OH:13])[C:6]=2[N:7]=1.Cl.[OH-:23].[Na+]>>[NH2:1][C:2]1[NH:3][C:4](=[O:23])[C:5]2[CH:10]=[CH:9][N:8]([C@@H:11]3[O:17][C@H:16]([CH2:18][OH:19])[C@@H:14]([OH:15])[C@@:12]3([CH3:20])[OH:13])[C:6]=2[N:7]=1 | C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1n1ccc2c(Cl)nc(N)nc21 | [OH-] | null | Cl | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | A mixture of product from Step B (90 mg, 0.3 mmol) in aqueous NaOH (2N, 9 mL) was heated at reflux temperature for 5 h, then neutralized at 0° C. with 2 N aqueous HCl and evaporated to dryness. Purification on a silica gel column with CH2Cl2/MeOH, 5/1 as eluent afforded the title compound as a white solid (70 mg). | C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1n1ccc2c(=O)[nH]c(N)nc21 | null | null | null |
1,328,137 | ord_dataset-cfad8b3f00044bcda60a96b019f09872 | null | 2013-01-01T00:08:00 | true | F[C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].C(=O)([O-])[O-].[K+].[K+].[C:16]1([SH:32])[C:29]2[C:30]3=[C:31]4[C:26](=[CH:27][CH:28]=2)[CH:25]=[CH:24][CH:23]=[C:22]4[CH:21]=[CH:20][C:19]3=[CH:18][CH:17]=1>CN(C=O)C>[CH:18]1[C:19]2[C:30]3=[C:31]4[C:22](=[CH:21][CH:20]=2)[CH:23]=[CH:24][CH:25]=[C:26]4[CH:27]=[CH:28][C:29]3=[C:16]([S:32][C:2]2[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=2[CH:4]=[O:5])[CH:17]=1 | O=Cc1ccccc1F | Sc1ccc2ccc3cccc4ccc1c2c34 | null | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | 130 | null | 2-fluoro-benzaldehyde (477 mg, 3.8 mmol), potassium carbonate (700 mg, 5.0 mmol) and pyrene-1-thiol (300 mg, 1.28 mmol) were dissolved in 15 mL of dry DMF under dry nitrogen, topped with a reflux condenser. The reaction mixture was heated to 130° C. for 24 h. After cooling the mixture was added to 50 mL of saturated potassium carbonate solution, and the mixture was extracted with 3 portions of ether. The extracts were dried with magnesium sulfate and evaporated. The residue of the crude product was further purified by chromatography on silica gel using 10:1 petroleum ether (60-80) and EtOAc as eluent to afford a yellow solid (200 mg, 46%). 1H-NMR (500 MHz, CDCl3): δ 6.56 (dd, J=0.8, 7.9 Hz, 1H), 7.07-7.22 (m, 2H), 7.89 (dd, J=1.7, 7.2 Hz, 1H), 8.02-8.28 (m, 8H), 8.58 (d, J=9.2 Hz, 1H), 10.45 (s, 1H). 13C-NMR (125 MHz, CDCl3): δ 124.7, 124.9, 125.3, 125.5, 125.9, 126.0, 126.4, 127.1, 128.0, 128.7, 129.0, 130.8, 131.0, 132.5, 133.3, 133.4, 133.8, 133.9, 137.0, 143.2, 191.6. EI-MS: m/z M+Calculated 338.1, found 338.1. | O=Cc1ccccc1Sc1ccc2ccc3cccc4ccc1c2c34 | null | 46.2 | null |
164,122 | ord_dataset-1385ebf1988241e49636101695ad79e4 | null | 1987-01-01T00:10:00 | true | [NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7](=[N:13][O:14][CH2:15][CH2:16][O:17][CH2:18][CH3:19])[C:8]([O:10][CH2:11][CH3:12])=[O:9])[N:6]=1.[C:20](OC(=O)C)(=[O:22])C>C(O)=O>[CH:20]([NH:1][C:2]1[S:3][CH:4]=[C:5]([C:7](=[N:13][O:14][CH2:15][CH2:16][O:17][CH2:18][CH3:19])[C:8]([O:10][CH2:11][CH3:12])=[O:9])[N:6]=1)=[O:22] | CC(=O)OC(C)=O | CCOCCON=C(C(=O)OCC)c1csc(N)n1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O=CO | null | null | null | null | null | null | null | null | null | null | null | null | Ethyl 2-(2-aminothiazol-4-yl)-2-(2-ethoxyethoxyimino)acetate (syn isomer, 11.5 g.), acetic anhydride (8.2 g.) and formic acid (3.7 g.) were treated in a similar manner to that of Example A-(4) to give ethyl 2-(2-formamidothiazol-4-yl)-2-(2-ethoxyethoxyimino)acetate (syn isomer, 8.6 g.). | CCOCCON=C(C(=O)OCC)c1csc(NC=O)n1 | null | 68.1 | null |
330,175 | ord_dataset-2c460e2ef9934444aaf26fec1f75741f | null | 1996-01-01T00:05:00 | true | [OH:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH:9]2[C:12]2([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[Cl:24])[CH2:15][C:14]([CH3:17])([CH3:16])[CH2:13]2)=[CH:4][C:3]=1[O:25][CH3:26].C=O.[C:29]([BH3-])#N.[Na+].[BrH:33]>CC(O)C.CO>[BrH:33].[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][N:8]([CH3:29])[CH:9]2[C:12]2([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[Cl:24])[CH2:15][C:14]([CH3:17])([CH3:16])[CH2:13]2)=[CH:4][C:3]=1[O:25][CH3:26] | COc1cc2c(cc1O)C(C1(c3ccccc3Cl)CC(C)(C)C1)NCC2 | [BH3-]C#N | null | Br | C=O | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(C)O | CO | null | null | null | null | null | null | null | null | null | 5 | 1.5 | A mixture of 7-hydroxy-6-methoxy-[1-(2-chlorophenyl)-3,3-dimethylcyclobutyl]-1,2,3,4-tetrahydroisoquinoline (3.7 g), methanol (50 ml) and 37-40% aqueous formaldehyde solution was cooled to 5° C. Sodium cyanoborohydride (1.4 g) was added and the mixture stirred for 1.5 hours. The solvents were removed by evaporation and the residue partitioned between water and dichloromethane. The organic layer was washed with aqueous ammonia solution and then brine, dried and the solvent removed by evaporation to give a gum which was dissolved in propan-2-ol. Addition of 48% aqueous hydrobromic acid gave 7-hydroxy-6-methoxy-2-methyl-1-[1-(2-chlorophenyl)-3,3-dimethylcyclobutyl]-1,2,3,4-tetrahydroisoquinoline hydrobromide, m.p. 202°-204° C. (dec). | COc1cc2c(cc1O)C(C1(c3ccccc3Cl)CC(C)(C)C1)N(C)CC2 | null | null | null |
1,682,401 | ord_dataset-3953983e052a4076aa7cc0880b79cb8b | null | 2016-01-01T00:01:00 | true | [Cl:1][C:2]1[CH:3]=[C:4]([CH:12]=[C:13](Cl)[N:14]=1)[C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6].O.[NH2:17][NH2:18]>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:12]=[C:13]([NH:17][NH2:18])[N:14]=1)[C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6] | NN | CC(C)(C)OC(=O)c1cc(Cl)nc(Cl)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | O | null | null | null | null | null | null | null | null | null | 75 | 18 | To a solution of tert-butyl 2,6-dichloroisonicotinate (11.0 g, 44.3 mmol) in ethanol (222 mL) was added hydrazine hydrate (6.46 mL, 133 mmol). The mixture was heated 75° C. After 18 h, the mixture was cooled to ambient temperature. The mixture was concentrate down to half of the volume. The solid crashed out was filtered off and the filtrate was concentrated to dryness: LC-MS [M+1]=244.1. | CC(C)(C)OC(=O)c1cc(Cl)nc(NN)c1 | null | null | null |
1,581,351 | ord_dataset-380e279f82154dba9e08ab51b3bdd08a | null | 2015-01-01T00:05:00 | true | Br[C:2]1[CH:3]=[C:4]([S:12]([NH:15][C@H:16]2[CH2:21][CH2:20][CH2:19][C@@H:18]([N:22]3[CH:26]=[N:25][N:24]=[CH:23]3)[CH2:17]2)(=[O:14])=[O:13])[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[CH2:27]([O:31]C=C)[CH2:28]CC.C(N(CC)CC)C>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:27]([C:2]1[CH:3]=[C:4]([S:12]([NH:15][C@H:16]2[CH2:21][CH2:20][CH2:19][C@@H:18]([N:22]3[CH:26]=[N:25][N:24]=[CH:23]3)[CH2:17]2)(=[O:14])=[O:13])[CH:5]=[C:6]([C:8]([F:11])([F:9])[F:10])[CH:7]=1)(=[O:31])[CH3:28] | O=S(=O)(N[C@H]1CCC[C@@H](n2cnnc2)C1)c1cc(Br)cc(C(F)(F)F)c1 | C=COCCCC | null | [Pd+2] | CC(=O)[O-] | 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 | 80 | 6 | Palladium acetate (9.9 mg, 0.044 mmol) was added to a stirred solution of 3a (100 mg, 0.221 mmol), n-butylvinyl ether (221 mg, 2.206 mmol) and triethylamine (92.0 μL, 0.662 mmol) in DMF (2.00 mL), and the resulting mixture was degassed and heated to 80° C. After 6 h, the reaction mixture was cooled to 0° C., 1M HCl was added, and the resulting mixture was allowed to warm to rt and stirred overnight. The reaction mixture was quenched with satd. aq. NaHCO3 and extracted with EtOAc. The combined organics were dried (MgSO4), filtered and concentrated in vacuo. The crude residue was purified by preparative thin layer chromatography on silica gel (10% MeOH/DCM as eluent) to afford the title compound, 9a. m/z (ES) 417 (MH)+ | CC(=O)c1cc(C(F)(F)F)cc(S(=O)(=O)N[C@H]2CCC[C@@H](n3cnnc3)C2)c1 | null | null | null |
794,440 | ord_dataset-744b04e8228742eb9aa4bde36f5dedf1 | null | 2007-01-01T00:10:00 | true | [C:1]([O:5][C:6](=[O:31])[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][C:18]2[N:19]=[C:20]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[O:21][CH:22]=2)=[CH:11][C:10]=1[CH:29]=[O:30])([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+]>C(O)C>[C:1]([O:5][C:6](=[O:31])[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][C:18]2[N:19]=[C:20]([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)[O:21][CH:22]=2)=[CH:11][C:10]=1[CH2:29][OH:30])([CH3:4])([CH3:2])[CH3:3] | CC(C)(C)OC(=O)CCc1ccc(OCCc2coc(-c3ccccc3)n2)cc1C=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 | 2 | A 100 mL round bottomed flask was charged with 3-{2-formyl-4-[2-(2-phenyloxazol-4-yl)ethoxy]phenyl}propionic acid tert-butyl ester (1.82 g, 4.18 mmol) and absolute ethanol (20 mL). The stirring solution was cooled in an ice/ethanol bath and treated with sodium borohydride (0.31 g, 8.36 mmol). The cold bath was removed, and the mixture was stirred at ambient temperature under a nitrogen atmosphere for 2 h. The reaction mixture was poured into EtOAc (100 mL) and ice water (100 mL). The organic layer was washed with brine, dried (Na2SO4), and concentrated to a yellow oil (1.62 g, 88%). 1H NMR (400 MHz, CDCl3) δ 1.38 (s, 9H), 2.37 (s, 3H), 2.54 (t, J=7.6 Hz, 2H), 2.88 (t, J=7.6 Hz, 2H), 2.97 (t, J=6.6 Hz, 2H), 4.23 (t, J=6.6 Hz, 2H), 4.66 (s, 2H), 6.78 (dd, J=8.3, 2.9 Hz, 1H), 6.94 (d, J=2.4 Hz, 1H), 7.09 (d, J=8.3 Hz, 1H), 7.38-7.45 (m, 3H), 7.97 (dd, J=8.1, 1.7 Hz, 2H). MS (ES) m/e 438 (M+1). | CC(C)(C)OC(=O)CCc1ccc(OCCc2coc(-c3ccccc3)n2)cc1CO | null | null | null |
193,981 | ord_dataset-b83b16f2fb1a4f8782f3d82c1766cc6b | null | 1989-01-01T00:08:00 | true | [H-].[Al+3].[Li+].[H-].[H-].[H-].[CH3:7][O:8][C:9]1[C:18]([F:19])=[CH:17][C:16]([F:20])=[C:15]([F:21])[C:10]=1[C:11](OC)=[O:12]>C(OCC)C>[CH3:7][O:8][C:9]1[C:18]([F:19])=[CH:17][C:16]([F:20])=[C:15]([F:21])[C:10]=1[CH2:11][OH:12] | COC(=O)c1c(F)c(F)cc(F)c1OC | null | null | [Al+3] | [H-] | [Li+] | 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 | null | Lithium aluminium hydride (1.5 g) was added in portions to a stirred mixture of methyl 2-methoxy-3,5,6-trifluorobenzoate (10.9 g) in dry diethyl ether (80 cm3) over a period of 30 minutes at the ambient temperature and the resultant mixture stirred for a further period of 30 minutes. The product, 2-methoxy-3,5,6-trifluorobenzyl alcohol (8.8 g), was isolated by a similar procedure to that illustrated in Example 6. | COc1c(F)cc(F)c(F)c1CO | null | 92.5 | null |
895,570 | ord_dataset-de6bce51790e4004a27e1a8f2bcc7ded | null | 2009-01-01T00:08:00 | true | [C:1]([O:5][C:6](=[O:19])[NH:7][CH:8]([CH3:18])[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([OH:16])=[C:12]([OH:17])[CH:11]=1)([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[K+].[K+].[CH2:26]([O:28][C:29](=[O:33])[CH:30](Br)Br)[CH3:27]>CN(C=O)C>[CH2:26]([O:28][C:29]([CH:30]1[O:16][C:13]2[CH:14]=[CH:15][C:10]([CH2:9][CH:8]([NH:7][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:19])[CH3:18])=[CH:11][C:12]=2[O:17]1)=[O:33])[CH3:27] | CC(Cc1ccc(O)c(O)c1)NC(=O)OC(C)(C)C | CCOC(=O)C(Br)Br | null | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | 120 | null | To 1.30 g (4.6 mmol) of 3C was added 40 ml of anhydrous DMF followed by 2.5 g (18 mmol) of anhydrous K2CO3, 2.5 g of 3 A° molecular sieves and 2.3 mL (17.7 mmol) of ethyldibromoacetate. The reaction mixture was heated at 120° C. for 3 hours under argon atmosphere and concentrated under reduced pressure. To the residue 100 mL of water and 75 mL of ethyl acetate were added and filtered. The filtrate was transferred to a separatory funnel and the organic layer was separated. The aqueous layer was extracted with 4×50 mL of ethyl acetate. All the organic layers were combined, dried (Na2SO4) and concentrated. The residue was purified by silica gel column chromatography using 20% ethyl acetate in hexane to give 413 mg (1.17 mmol, 26%) of 3D as a colorless gum (M+Na, 374). | CCOC(=O)C1Oc2ccc(CC(C)NC(=O)OC(C)(C)C)cc2O1 | null | 25.4 | null |
1,641,894 | ord_dataset-bcc0b01d4f58457a8733b10a099f43ba | null | 2015-01-01T00:10:00 | true | [Br:1][C:2]1[CH:9]=[CH:8][C:5](C=O)=[CH:4][N:3]=1.[CH:10]([O:17][CH2:18][CH3:19])([O:14][CH2:15][CH3:16])OCC>C(O)C.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH:10]([O:14][CH2:15][CH3:16])[O:17][CH2:18][CH3:19])=[CH:4][N:3]=1 | O=Cc1ccc(Br)nc1 | CCOC(OCC)OCC | null | Cc1ccc(S(=O)(=O)O)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | O | null | null | null | null | null | null | null | null | null | null | null | In ethanol (60 mL) was dissolved 6-bromonicotinaldehyde (2.00 g, 10.8 mmol). Triethyl orthoformate (5.37 mL, 32.3 mmol) and p-toluenesulfonic acid monohydrate (102 mg, 0.538 mmol) were added and the mixture was refluxed for 2 hours. The solvent in the reaction mixture was evaporated under reduced pressure, and a saturated aqueous sodium bicarbonate solution and water were added. Extraction with ethyl acetate, washing with saturated brine and drying over anhydrous sodium sulfate were performed. After filtration, the solvent in the filtrate was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=9/1) to give 2-bromo-5-(diethoxymethyl)pyridine (2.59 g, 92% yield). | CCOC(OCC)c1ccc(Br)nc1 | null | 92.2 | null |
426,926 | ord_dataset-1ecf96d88f254270bff816ee7eeffef6 | null | 1999-01-01T00:02:00 | true | S([O-])([O-])(=O)=O.[Mg+2].[CH:7]1[C:12]([C@@H:13](O)[CH2:14]N)=[CH:11][C:10]([OH:17])=[C:9](O)[CH:8]=1.[C:19]([O:22][CH2:23][CH3:24])(=O)[CH3:20]>[Pt]>[CH2:23]([O:22][C:19]1[CH:20]=[CH:11][C:12]([CH2:7][CH2:8][CH2:9][CH:10]=[O:17])=[CH:13][CH:14]=1)[C:24]1[CH:11]=[CH:12][CH:7]=[CH:8][CH:9]=1 | NC[C@H](O)c1ccc(O)c(O)c1 | CCOC(C)=O | null | [Pt] | O=S(=O)([O-])[O-] | [Mg+2] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | A solution of 4-(4-benzyloxyphenyl)-butanal (52.4 g, 206 mmol) in 150 mL ethyl acetate (1.4M solution) was prepared and set aside. 10% platinum on carbon (3.40 g) was prewetted with ethyl acetate and transferred to the reactor. To this was added magnesium sulfate (60.0 g, 500 mmol), followed by the ethyl acetate solution of (trimethylsilyl)-protected norepinephrine prepared as described in Example 1. | O=CCCCc1ccc(OCc2ccccc2)cc1 | null | null | null |
882,324 | ord_dataset-3592bd645cd143ee8274cd0d834ae581 | null | 2009-01-01T00:05:00 | true | [CH2:1]([O:8][C:9]([N:11]1[CH2:25][CH2:24][C:14]2([O:18][C:17](=[O:19])[NH:16][CH:15]2[CH2:20][CH2:21][CH2:22][CH3:23])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH:28]1([CH2:34]Br)[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1>CN(C=O)C.CCOC(C)=O>[CH2:1]([O:8][C:9]([N:11]1[CH2:12][CH2:13][C:14]2([O:18][C:17](=[O:19])[N:16]([CH2:34][CH:28]3[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]3)[CH:15]2[CH2:20][CH2:21][CH2:22][CH3:23])[CH2:24][CH2:25]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1 | CCCCC1NC(=O)OC12CCN(C(=O)OCc1ccccc1)CC2 | BrCC1CCCCC1 | null | [H-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | CCOC(C)=O | null | null | null | null | null | null | null | null | null | 70 | 0.08 | To a solution of 5.0 g 4-butyl-2-oxo-1-oxa-3,8-diaza-spiro[4.5]decane-8-carboxylic acid benzyl ester (14.4 mmol) in 50 mL DMF was added 994 mg of sodium hydride (21.6 mmol, 60% dispersion in mineral oil). The reaction mixture stirred for five minutes and 2.2 mL of cyclohexylmethyl bromide (15.8 mmol) was then added. The reaction mixture stirred under nitrogen for 18 h. The reaction mixture was heated to 70° C. for three h. The reaction mixture cooled to room temperature and was diluted with 500 mL EtOAc and washed twice with water, once with brine. The organics were dried over magnesium sulfate and evaporated under reduced pressure. The residue was purified by flash chromatography on silica gel utilizing a gradient elution (10% to 15% EtOAc/DCM) to provide 4.1 g (65%) of 4-butyl-3-cyclohexylmethyl-2-oxo-1-oxa-3,8-diaza-spiro[4.5]decane-8-carboxylic acid benzyl ester: ms [M]+=443. | CCCCC1N(CC2CCCCC2)C(=O)OC12CCN(C(=O)OCc1ccccc1)CC2 | null | 64.3 | null |
881,169 | ord_dataset-3592bd645cd143ee8274cd0d834ae581 | null | 2009-01-01T00:05:00 | true | [F:1][C:2]1[CH:29]=[C:28]([N+:30]([O-])=O)[CH:27]=[CH:26][C:3]=1[O:4][C:5]1[N:10]=[CH:9][N:8]=[C:7]([NH:11][C:12]([N:14]2[CH2:19][CH2:18][N:17]([CH2:20][CH2:21][N:22]3[CH2:25][CH2:24][CH2:23]3)[CH2:16][CH2:15]2)=[O:13])[CH:6]=1>O1CCCC1.CO.[C].[Pd]>[NH2:30][C:28]1[CH:27]=[CH:26][C:3]([O:4][C:5]2[N:10]=[CH:9][N:8]=[C:7]([NH:11][C:12]([N:14]3[CH2:19][CH2:18][N:17]([CH2:20][CH2:21][N:22]4[CH2:25][CH2:24][CH2:23]4)[CH2:16][CH2:15]3)=[O:13])[CH:6]=2)=[C:2]([F:1])[CH:29]=1 | O=C(Nc1cc(Oc2ccc([N+](=O)[O-])cc2F)ncn1)N1CCN(CCN2CCC2)CC1 | null | null | [Pd] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | CO | null | null | null | null | null | null | null | null | null | null | 16.5 | 4-[2-(Azetidin-1-yl)ethyl]piperazine-1-carboxylic acid [6-(2-fluoro-4-nitrophenoxy)pyrimidin-4-yl]amide (110 mg) was dissolved in tetrahydrofuran (3 ml) and methanol (3 ml), and then 10% palladium carbon (53 mg) was added, followed by stirring under a hydrogen atmosphere for 16.5 hrs. The catalyst was filtered off and washed with methanol. The filtrate and washings were concentrated under reduced pressure to give a residue, which was then purified by silica gel column chromatography (Fuji Silysia NH, heptane: ethyl acetate:ethanol=95:5 to 90:10). Fractions containing the target compound were concentrated to provide a crude product of the titled compound (32.4 mg) as a yellow oil. | Nc1ccc(Oc2cc(NC(=O)N3CCN(CCN4CCC4)CC3)ncn2)c(F)c1 | null | 31.6 | null |
286,550 | ord_dataset-3577d334f6eb4dc4bd73564fee3f0dfc | null | 1994-01-01T00:03:00 | true | [Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[C:7]([Cl:9])[CH:8]=1)[NH2:5].[CH:10]([NH:12][CH:13]([C:19]([O-])=[O:20])[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[O:11].C1(N=C=NC2CCCCC2)CCCCC1>>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:19](=[O:20])[CH:13]([NH:12][CH:10]=[O:11])[C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH:6]=[C:7]([Cl:9])[CH:8]=1 | Nc1cc(Cl)cc(Cl)c1 | CCOC(=O)C(NC=O)C(=O)[O-] | null | C(=NC1CCCCC1)=NC1CCCCC1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | 3,5-Dichloroaniline, mono-ethyl formamidomalonate and 1,3-dicyclohexylcarbodiimide were reacted in a manner similer to that described in Example XCI Part B to give ethyl 3-[(3,5-dichlorophenyl)amino]-2-formamido-3-oxopropanoate having a melting point of 147.0° C.-148.0° C. Elemental analysis of the product indicated the following: | CCOC(=O)C(NC=O)C(=O)Nc1cc(Cl)cc(Cl)c1 | null | null | null |
1,745,974 | ord_dataset-60a3e71da3174666a50a61dcfa611a9f | null | 2016-01-01T00:07:00 | true | [NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C@H:9]([C:11]2[N:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:15](=[O:23])[C:14]3=[C:24](C)[CH:25]=[CH:26][N:13]3[N:12]=2)[CH3:10])[C:3]=1I.C([Sn](CCCC)(CCCC)[C:34]1[S:35][CH:36]=[CH:37][N:38]=1)CCC.[Cl-].C(N(CC)CC)C>CN(C)C=O.[Cu]I>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C@H:9]([C:11]2[N:16]([C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:15](=[O:23])[C:14]3=[CH:24][CH:25]=[CH:26][N:13]3[N:12]=2)[CH3:10])[C:3]=1[C:34]1[S:35][CH:36]=[CH:37][N:38]=1 | CCCC[Sn](CCCC)(CCCC)c1nccs1 | Cc1ccn2nc([C@H](C)Nc3ncnc(N)c3I)n(-c3ccccc3)c(=O)c12 | null | [Cu]I | [Cl-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(CC)CC | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | null | 60 mg (0.07 mmol) of (S)-2-(1-((6-amino-5-iodopyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one, 43 mg (0.11 mmol) of 2-(tributylstannyl)thiazole, 2.0 mg (0.01 mmol) of bis-triphenylphosphinepalladium(II) chloride, 4.4 mg (0.02 mmol) of copper (I) iodide and 32 μl (0.23 mmol) of triethylamine in dimethylformamide (1.5 mL) were heated to 120° C. for 20 minutes with microwave irradiation under nitrogen atmosphere. The reaction mixture was filtered through Celite® and washed with methanol. The solvent of the filtrates were evaporated in vacuum and the residue was dissolved in ethyl acetate and washed with brine, dried over magnesium sulphate, filtered and the solvent was removed. The product was purified first by reverse phase chromatography (C-18 silica from Waters®, water/1:1 acetonitrile-methanol as eluents [0.1% v/v formic acid buffered] 0% to 100%) and then by preparative HPLC (Waters XBridge C18 OBD column, mixture of eluents NB from 50% B to 65% B, in a 10 min. gradient) to give 4 mg (13% yield) of the title compound. | C[C@H](Nc1ncnc(N)c1-c1nccs1)c1nn2cccc2c(=O)n1-c1ccccc1 | null | 13.3 | null |
838,595 | ord_dataset-074f86301ec5441ab3b52d902ac06949 | null | 2008-01-01T00:09:00 | true | C[O:2][C:3]([C:5]1([C:10]2[CH:15]=[C:14]([F:16])[CH:13]=[C:12]([F:17])[CH:11]=2)[CH2:9][CH2:8][CH2:7][CH2:6]1)=[O:4].[OH-].[K+]>CS(C)=O.O>[F:16][C:14]1[CH:15]=[C:10]([C:5]2([C:3]([OH:4])=[O:2])[CH2:9][CH2:8][CH2:7][CH2:6]2)[CH:11]=[C:12]([F:17])[CH:13]=1 | COC(=O)C1(c2cc(F)cc(F)c2)CCCC1 | null | null | [K+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CS(C)=O | O | null | null | null | null | null | null | null | null | null | 25 | 2.5 | To a solution of 1-(3,5-difluorophenyl)cyclopentanecarboxylic acid methyl ester (Step A, 2.0 g, 8.3 mmol) in dimethylsulfoxide (5 mL) was added potassium hydroxide (1.9 g, 33 mol) in 2 mL of water. After stirring at room temperature for 2.5 h, the reaction mixture was partitioned between ether (50 mL) and saturated aqueous hydrochloric acid (2 N, 50 mL). The organic layer was separated and the aqueous layer extracted with ether (2×50 mL). The combined extracts were dried over anhydrous sodium sulfate, filtered, and concentrated to dryness to give the title compound. 1H NMR (400 MHz, CD3OD): δ 6.97 (m, 2H), 6.80 (m. 1H), 2.60 (m, 2H), 1.84 (m, 2H), 1.74 (m, 4H). | O=C(O)C1(c2cc(F)cc(F)c2)CCCC1 | null | null | null |
1,074,014 | ord_dataset-5df93261afc143c3ae919a57ff4fc1d4 | null | 2011-01-01T00:07:00 | true | [Br:1][C:2]1[CH:3]=[N:4][C:5]2[N:6]([N:8]=[C:9]([C:11]([OH:13])=O)[CH:10]=2)[CH:7]=1.[N:14]1([C:20]2[CH:29]=[C:28]3[C:23]([CH2:24][CH2:25][NH:26][CH2:27]3)=[CH:22][CH:21]=2)[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1>>[Br:1][C:2]1[CH:3]=[N:4][C:5]2[N:6]([N:8]=[C:9]([C:11]([N:26]3[CH2:25][CH2:24][C:23]4[C:28](=[CH:29][C:20]([N:14]5[CH2:19][CH2:18][O:17][CH2:16][CH2:15]5)=[CH:21][CH:22]=4)[CH2:27]3)=[O:13])[CH:10]=2)[CH:7]=1 | c1cc2c(cc1N1CCOCC1)CNCC2 | O=C(O)c1cc2ncc(Br)cn2n1 | null | null | null | null | null | null | null | 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 close analogy to the procedure described in Example 1, 6-bromo-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid is reacted with 7-Morpholin-4-yl-1,2,3,4-tetrahydro-isoquinoline to provide the title compound in moderate yield. | O=C(c1cc2ncc(Br)cn2n1)N1CCc2ccc(N3CCOCC3)cc2C1 | null | null | null |
1,323,691 | ord_dataset-cfad8b3f00044bcda60a96b019f09872 | null | 2013-01-01T00:08:00 | true | [CH2:1]([C:5]1=[CH:6][N:7]([C:24]([CH3:27])([CH3:26])[CH3:25])[S:8]/[C:9]/1=[N:10]\[C:11]([C@:13]1([CH3:23])[CH2:17][CH2:16][C@H:15]([C:18](O)=[O:19])[C:14]1([CH3:22])[CH3:21])=[O:12])[CH2:2][CH2:3][CH3:4].Cl.[CH2:29]([NH2:31])[CH3:30]>>[CH2:1]([C:5]1=[CH:6][N:7]([C:24]([CH3:27])([CH3:25])[CH3:26])[S:8]/[C:9]/1=[N:10]\[C:11]([C@:13]1([CH3:23])[CH2:17][CH2:16][C@H:15]([C:18]([NH:31][CH2:29][CH3:30])=[O:19])[C:14]1([CH3:21])[CH3:22])=[O:12])[CH2:2][CH2:3][CH3:4] | CCN | CCCCc1cn(C(C)(C)C)s/c1=N\C(=O)[C@]1(C)CC[C@H](C(=O)O)C1(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 | null | null | The product from Example 173 and ethylamine hydrochloride (Aldrich) were processed using the method described in Example 178 to afford the title compound. 1H NMR (DMSO-d6) δ 0.48 (s, 3H), 0.90 (t, J=7.0 Hz, 3H), 1.00 (t, J=7.2 Hz, 3H), 1.23 (2, 3H), 1.19 (s, 3H), 1.26-1.44 (m, 3H), 1.57 (s, 9H), 1.57-1.70 (m, 3H), 1.96-2.09 (m, 1H), 2.59-2.67 (m, 3H), 2.72-2.82 (m, 1H), 2.94-3.19 (m, 2H), 7.53-7.57 (m, 1H), 8.50 (s, 1H). MS (ESI+) m/z 422 (M+H)+. Anal. calcd. for C23H39N3O2S: C, 65.52; H, 9.32; N, 9.97. Found: C, 65.03; H, 9.26; N, 9.86. | CCCCc1cn(C(C)(C)C)s/c1=N\C(=O)[C@]1(C)CC[C@H](C(=O)NCC)C1(C)C | null | null | null |
1,375,689 | ord_dataset-d23f2f15886d4c22b7d7ba5f0e203e81 | null | 2013-01-01T00:12:00 | true | [C:1]([O:5][CH:6]([C:11]1[C:12]([C:21]2[CH:22]=[C:23]3[C:28](=[CH:29][CH:30]=2)[O:27][CH2:26][CH2:25][CH2:24]3)=[C:13]2[CH:20]=[CH:19][NH:18][C:14]2=[N:15][C:16]=1[CH3:17])[C:7]([O:9]C)=[O:8])([CH3:4])([CH3:3])[CH3:2].[F:31][C:32]1[CH:39]=[C:38]([F:40])[CH:37]=[C:36]([F:41])[C:33]=1[CH2:34]Br>>[C:1]([O:5][CH:6]([C:11]1[C:12]([C:21]2[CH:22]=[C:23]3[C:28](=[CH:29][CH:30]=2)[O:27][CH2:26][CH2:25][CH2:24]3)=[C:13]2[CH:20]=[CH:19][N:18]([CH2:34][C:33]3[C:32]([F:31])=[CH:39][C:38]([F:40])=[CH:37][C:36]=3[F:41])[C:14]2=[N:15][C:16]=1[CH3:17])[C:7]([OH:9])=[O:8])([CH3:4])([CH3:3])[CH3:2] | COC(=O)C(OC(C)(C)C)c1c(C)nc2[nH]ccc2c1-c1ccc2c(c1)CCCO2 | Fc1cc(F)c(CBr)c(F)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The title compound was prepared in a manner similar to that described in Example 27, Step H from methyl 2-(tert-butoxy)-2-(4-(chroman-6-yl)-6-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)acetate and 2,4,6-trifluorobenzyl bromide. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.41 (s, 1 H), 7.20 (d, J=10.0 Hz, 1 H), 7.08 (t, J=4.0 Hz, 1 H), 6.91 (dd, J=5.6, 8.3 Hz, 1 H), 6.71 (t, J=8.1 Hz, 2 H), 6.23-6.16 (m, 1 H), 5.61-5.42 (m, 3 H), 4.31-4.24 (m, 2 H), 2.94-2.76 (m, 2 H), 2.72 (s, 3 H), 2.13-2.05 (m, 2 H), 0.96 (s, 9 H); LC/MS (m/z) ES+=539.33 (M+1). | Cc1nc2c(ccn2Cc2c(F)cc(F)cc2F)c(-c2ccc3c(c2)CCCO3)c1C(OC(C)(C)C)C(=O)O | null | null | null |
1,512,618 | ord_dataset-1a1aa5d1c3224edca0aec6e3398da985 | null | 2014-01-01T00:11:00 | true | [I:1][C:2]1[N:6]2[CH:7]=[CH:8][C:9]([CH2:11][OH:12])=[CH:10][C:5]2=[N:4][CH:3]=1.C[N+]1([O-])CCOCC1>C(Cl)Cl.CCC[N+](CCC)(CCC)CCC.[O-][Ru](=O)(=O)=O>[I:1][C:2]1[N:6]2[CH:7]=[CH:8][C:9]([CH:11]=[O:12])=[CH:10][C:5]2=[N:4][CH:3]=1 | OCc1ccn2c(I)cnc2c1 | null | null | O=[Ru](=O)(=O)[O-] | CCC[N+](CCC)(CCC)CCC | C[N+]1([O-])CCOCC1 | 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 | 18 | To a solution of (3-Iodo-imidazo[1,2-a]pyridin-7-yl)methanol (1.00 g, 3.65 mmol) and NMO (0.64 g, 5.47 mmol) in CH2Cl2 (30 ml) with sieves (3 g) at 0° C. was added TPAP (0.06 g, 0.18 mmol). The reaction mixture was allowed to warm to room temperature and stirred for 18 h, before being filtered to remove the sieves. The organic layer was washed with H2O (×2), dried (MgSO4), filtered and the solvent removed in vacuo. The residue was purified by silica column chromatography (0-60% MeOH in Et2O) to afford the product (0.15 g). MS: [M+H]+=273 | O=Cc1ccn2c(I)cnc2c1 | null | 15.1 | null |
804,268 | ord_dataset-ed846b4b229e4bb09ad9dba95ad7ebeb | null | 2008-01-01T00:01:00 | true | [CH3:1][C:2]1([CH3:20])[C:10]2[C:5](=[CH:6][CH:7]=[C:8](OS(C(F)(F)F)(=O)=O)[CH:9]=2)[C:4](=[O:19])[CH2:3]1.[C:21]([C:23]1[CH:24]=[C:25](B(O)O)[CH:26]=[CH:27][CH:28]=1)#[N:22]>>[CH3:1][C:2]1([CH3:20])[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:27]3[CH:28]=[C:23]([CH:24]=[CH:25][CH:26]=3)[C:21]#[N:22])[CH:9]=2)[C:4](=[O:19])[CH2:3]1 | CC1(C)CC(=O)c2ccc(OS(=O)(=O)C(F)(F)F)cc21 | N#Cc1cccc(B(O)O)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The title compound was prepared from trifluoro-methanesulfonic acid 3,3-dimethyl-1-oxo-indan-5-yl ester and 3-cyanophenyl boronic acid according to the procedure described in example 21. MS (ESI) m/z 262; HRMS: calcd for C18H15NO+H+, 262.12264; found (ESI, [M+H]+), 262.1219. | CC1(C)CC(=O)c2ccc(-c3cccc(C#N)c3)cc21 | null | null | null |
1,003,428 | ord_dataset-70899a0178cc441482746c093624afa0 | null | 2010-01-01T00:10:00 | true | Br[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([O:11][C@H:12]2[CH2:17][CH2:16][C@H:15]([CH3:18])[CH2:14][CH2:13]2)=[CH:7][CH:6]=1)=O.[C:19]([O:23][C:24](=[O:36])[CH2:25][CH2:26][N:27]([CH:31]1[CH2:35][CH2:34][CH2:33][CH2:32]1)[C:28]([NH2:30])=[S:29])([CH3:22])([CH3:21])[CH3:20]>CN1C(=O)CCC1>[C:19]([O:23][C:24](=[O:36])[CH2:25][CH2:26][N:27]([CH:31]1[CH2:35][CH2:34][CH2:33][CH2:32]1)[C:28]1[S:29][CH:2]=[C:3]([C:5]2[CH:10]=[CH:9][C:8]([O:11][C@H:12]3[CH2:17][CH2:16][C@H:15]([CH3:18])[CH2:14][CH2:13]3)=[CH:7][CH:6]=2)[N:30]=1)([CH3:22])([CH3:20])[CH3:21] | C[C@H]1CC[C@H](Oc2ccc(C(=O)CBr)cc2)CC1 | CC(C)(C)OC(=O)CCN(C(N)=S)C1CCCC1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN1CCCC1=O | null | null | null | null | null | null | null | null | null | null | 25 | 8 | The 2-bromo-1-[4-(trans-4-methyl-cyclohexyloxy)-phenyl]-ethanone (764 mg, 3.44 mmol), 3-(1-cyclopentyl-thioureido)-propionic acid tert-butyl ester (935 mg, 2.46 mmol), NMP (6 mL) were combined as indicated in general procedure B. The reaction was stirred at room temperature overnight. After an aqueous work up, the crude product was purified by silica gel chromatography (gradient, hexane→3% EtOAc-hexane) to afford 3-(cyclopentyl-{4-[4-(trans-4-methyl-cyclohexyloxy)-phenyl]-thiazol-2-yl}-amino)-propionic acid tert-butyl ester (1.05 g). | CC(C)(C)OC(=O)CCN(c1nc(-c2ccc(O[C@H]3CC[C@H](C)CC3)cc2)cs1)C1CCCC1 | null | null | null |
821,423 | ord_dataset-ec58fad8331a42c5a67ad75aac6713b4 | null | 2008-01-01T00:05:00 | true | [CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([NH:10][C:11](=[O:21])[C@@H:12]([NH2:20])[CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[S:8][CH:9]=1)=[O:4].[C:22]([O:26][C:27]([NH:29][C@H:30]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C:31](O)=[O:32])=[O:28])([CH3:25])([CH3:24])[CH3:23].C(N(C(C)C)CC)(C)C.ON1C2C=CC=CC=2N=N1.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>CN(C)C=O>[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([NH:10][C:11](=[O:21])[C@@H:12]([NH:20][C:31](=[O:32])[C@H:30]([NH:29][C:27]([O:26][C:22]([CH3:24])([CH3:23])[CH3:25])=[O:28])[C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[S:8][CH:9]=1)=[O:4] | CC(C)(C)OC(=O)N[C@@H](C(=O)O)c1ccccc1 | COC(=O)c1csc(NC(=O)[C@@H](N)Cc2ccccc2)n1 | null | CN(C)C(On1nnc2ccccc21)=[N+](C)C | On1nnc2ccccc21 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(C(C)C)C(C)C | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | 0.08 | A solution of 2-((S)-2-amino-3-phenyl-propionylamino)-thiazole-4-carboxylic acid methyl ester (prepared as described in example 3, step c) (0.61 g, 2.0 mmol), (R)-tert-butoxycarbonylamino-phenylacetic acid (0.55 g, 2.2 mmol), diisopropylethylamine (1.40 mL, 7.88 mmol) and 1-hydroxybenzotriazole (0.324 g, 2.40 mmol) in N,N-dimethylformamide (5 mL) was stirred in an ice bath for 5 minutes To the cooled yellow-orange solution was added O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexaflurorophosphate (0.91 g, 2.40 mmol). The reaction mixture was stirred for 5 minutes and the ice bath was removed and stirring continued for 1 hour. The reaction mixture was then diluted with ethyl acetate, washed brine and the aqueous layer extracted with ethyl acetate. The combined organic extracts were passed through a pad of sodium sulfate layered on the top of a pad of silica gel contained in a 60 mL vacuum filtration funnel. Residual material was eluted from the pad of sodium sulfate and silica gel with ethyl acetate and the filtrate was concentrated in vacuo to give —[(S)-2-((R)-2-tert-butoxycarbonylamino-2-phenyl-acetylamino)-3-phenyl-propionylamino]-thiazole-4-carboxylic acid methyl ester which was taken into dry dichloromethane (10 mL) under argon and cooled in an ice bath. To this was added trifluoroacetic acid (5 mL, 64.9 mmol) and the mixture stirred at 0° C. for 2 hours. The reaction mixture was then concentrated to dryness. The residue was taken into dichloromethane and precipited with ether and the suspension was stirred for 15 minutes. The solid was isolated by filtration and washed with ether and dried to give a tan solid. The solid was taken into dichloromethane and washed with saturated aqueous sodium bicarbonate solution. The organic layer was separated, dried over sodium sulfate, filtered, concentrated and dried to give 2-[(S)-2-((R)-2-amino-2-phenyl-acetylamino)-3-phenyl-propionylamino]-thiazole-4-carboxylic acid methyl ester as an off white foam (0.80 g, 91%). | COC(=O)c1csc(NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](NC(=O)OC(C)(C)C)c2ccccc2)n1 | null | null | null |
1,654,213 | ord_dataset-42cd9bc5aae3485f9a58f1527bd3abf0 | null | 2015-01-01T00:11:00 | true | [NH+]1C=CC=CC=1.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[OH:18][CH:19]1[CH2:24][CH2:23][CH:22]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH2:21][CH2:20]1.[O:30]1[CH:35]=[CH:34][CH2:33][CH2:32][CH2:31]1>C(Cl)Cl>[O:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH:31]1[O:18][CH:19]1[CH2:20][CH2:21][CH:22]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH2:23][CH2:24]1 | C1=COCCC1 | CCOC(=O)C1CCC(O)CC1 | null | Cc1ccc(S(=O)(=O)[O-])cc1 | c1cc[nH+]cc1 | 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 | Pyridinium-4-toluenesulfonate (2.57 g, 10.2 mmol) was added to a solution of ethyl 4-hydroxycyclohexanecarboxylate (8.8 g, 51.10 mmol) and 3,4-dihydro-2H-pyran (8.60 g, 102 mmol) in DCM (200 mL). After 16 hours the reaction was quenched with saturated aqueous sodium bicarbonate. The layers were separated and the organic layer was washed with water. The organic layer was dried (Na2SO4), filtered and concentrated. Purification by flash column chromatography on an Analogix SF65-200 g column (hexanes/ethyl acetate 95:05-9:1) afforded the title compound (clear oil) as a mixture of isomers (11.1 g, 85%). | CCOC(=O)C1CCC(OC2CCCCO2)CC1 | null | null | null |
1,322,887 | ord_dataset-cfad8b3f00044bcda60a96b019f09872 | null | 2013-01-01T00:08:00 | true | Cl[C:2]1[CH:29]=[CH:28][C:5]([C:6]([NH:8][CH2:9][C:10]2[C:19](=[O:20])[C:18]3[C:13](=[CH:14][C:15]([Cl:21])=[CH:16][CH:17]=3)[N:12]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH:11]=2)=[O:7])=[CH:4][N:3]=1.Cl.[CH3:31][S:32]([CH:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1)(=[O:34])=[O:33]>>[Cl:21][C:15]1[CH:14]=[C:13]2[C:18]([C:19](=[O:20])[C:10]([CH2:9][NH:8][C:6]([C:5]3[CH:28]=[CH:29][C:2]([N:38]4[CH2:39][CH2:40][CH:35]([S:32]([CH3:31])(=[O:34])=[O:33])[CH2:36][CH2:37]4)=[N:3][CH:4]=3)=[O:7])=[CH:11][N:12]2[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[CH:17][CH:16]=1 | O=C(NCc1cn(-c2ccccc2)c2cc(Cl)ccc2c1=O)c1ccc(Cl)nc1 | CS(=O)(=O)C1CCNCC1 | 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 | 4-Methanesulfonyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-carboxylic acid (7-chloro-4-oxo-1-phenyl-1,4-dihydro-quinolin-3-ylmethyl)-amide was prepared starting from intermediate E and 4-methanesulfonyl piperidine hydrochloride. MS calcd. for C28H27ClN4O4S [(M+H)+] 551.1, obsd. 551. | CS(=O)(=O)C1CCN(c2ccc(C(=O)NCc3cn(-c4ccccc4)c4cc(Cl)ccc4c3=O)cn2)CC1 | null | null | null |
557,756 | ord_dataset-f483e698250b4da0a84f425c7bfa965a | null | 2002-01-01T00:08:00 | true | [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([O:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:13][CH:12]=2)=[CH:6][C:5]=1[N:24]([CH3:32])[C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])([O-])=O>[Pd].C1(C)C=CC=CC=1.CO>[NH2:1][C:4]1[CH:9]=[CH:8][C:7]([O:10][C:11]2[CH:12]=[CH:13][C:14]([O:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:15][CH:16]=2)=[CH:6][C:5]=1[N:24]([CH3:32])[C:25](=[O:31])[O:26][C:27]([CH3:28])([CH3:29])[CH3:30] | CN(C(=O)OC(C)(C)C)c1cc(Oc2ccc(Oc3ccccc3)cc2)ccc1[N+](=O)[O-] | null | null | [Pd] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | Cc1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | In a similar manner to that described in Reference Example 7, a reaction was carried out using t-butyl N-[2-nitro-5-(4-phenoxyphenoxy)phenyl]-N-methylcarbamate (8.6 g), palladium on carbon (10%, 0.6 g) and toluene/methanol=16/3 (190 ml) and the reaction mixture was purified to give the title compound (7.2 g). | CN(C(=O)OC(C)(C)C)c1cc(Oc2ccc(Oc3ccccc3)cc2)ccc1N | null | 89.9 | null |
1,328,296 | ord_dataset-cfad8b3f00044bcda60a96b019f09872 | null | 2013-01-01T00:08:00 | true | [C:1]1([CH:7]2[CH2:12][CH2:11][C:10](=O)[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:14]([O:18][C:19](=[O:25])[NH:20][CH:21]1[CH2:24][NH:23][CH2:22]1)([CH3:17])([CH3:16])[CH3:15]>>[C:14]([O:18][C:19](=[O:25])[NH:20][CH:21]1[CH2:24][N:23]([CH:10]2[CH2:11][CH2:12][CH:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH2:8][CH2:9]2)[CH2:22]1)([CH3:17])([CH3:15])[CH3:16] | O=C1CCC(c2ccccc2)CC1 | CC(C)(C)OC(=O)NC1CNC1 | null | null | null | null | null | null | null | 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 as a white solid by reductive amination of 4-phenyl-cyclohexanone and azetidin-3-yl-carbamic acid tert-butyl ester using the procedure described in Step D of Example 1. | CC(C)(C)OC(=O)NC1CN(C2CCC(c3ccccc3)CC2)C1 | null | null | null |
1,523,831 | ord_dataset-8c74302143c04eb9983e4b3a7ead2d72 | null | 2014-01-01T00:12:00 | true | [C:1]([C:6]1[CH:11]=[CH:10][C:9]([S:12](Cl)(=[O:14])=[O:13])=[CH:8][CH:7]=1)([CH2:4][CH3:5])([CH3:3])[CH3:2].[CH3:16][C:17]1[CH:21]=[C:20]([NH2:22])[N:19]([C:23]2[CH:32]=[CH:31][CH:30]=[C:29]3[C:24]=2[CH:25]=[CH:26][CH:27]=[N:28]3)[N:18]=1.ClCCl>N1C=CC=CC=1>[CH3:16][C:17]1[CH:21]=[C:20]([NH:22][S:12]([C:9]2[CH:10]=[CH:11][C:6]([C:1]([CH2:4][CH3:5])([CH3:3])[CH3:2])=[CH:7][CH:8]=2)(=[O:14])=[O:13])[N:19]([C:23]2[CH:32]=[CH:31][CH:30]=[C:29]3[C:24]=2[CH:25]=[CH:26][CH:27]=[N:28]3)[N:18]=1 | CCC(C)(C)c1ccc(S(=O)(=O)Cl)cc1 | Cc1cc(N)n(-c2cccc3ncccc23)n1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | c1ccncc1 | null | null | null | null | null | null | null | null | null | 80 | null | A mixture of 4-t-pentylbenzenesulfonyl chloride (0.13 g, 0.53 mmol) and 3-methyl-1-(quinolin-5-yl)-1H-pyrazol-5-amine (prepared from Example 4 step b, 0.10 g, 0.44 mmol) in pyridine (1.0 mL) was heated at 80° C. for 3 h with stirring. After cooling to room temperature, dichloromethane was added to the reaction mixture and washed with 1 M aqueous sodium hydrogen sulfate (1 mL). The aqueous layer was further extracted with dichloromethane (2×5 mL), and the combined organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. The crude residue was purified by reverse phase HPLC(C18 column, acetonitrile-H2O with 0.1% TFA as eluent) to give the title compound as a white solid (0.11 g, 0.24 mmol, 55%). 1H NMR (400 MHz, CDCl3) δ 8.96 (dd, J=1.6, 4.8 Hz, 1H), 8.20 (d, J=8.8 Hz, 1H), 8.13 (d, J=8.4 Hz, 1H), 7.75 (d, J=7.6 Hz, 1H), 7.71 (s, 1H), 7.69 (s, 1H), 7.54 (dd, J=4.8, 8.4 Hz, 1H), 7.46-7.43 (m, 3H), 6.02 (s, 1H), 2.32 (s, 3H), 1.70 (q, J=7.2 Hz, 2H), 1.34 (s, 6H), 0.70 (t, J=7.2 Hz, 3H); MS: (ES) m/z calculated for C24H27N4O2S [M+H]+ 435.2. found 435.1. | CCC(C)(C)c1ccc(S(=O)(=O)Nc2cc(C)nn2-c2cccc3ncccc23)cc1 | null | 54.5 | null |
80,834 | ord_dataset-f196f0a87dd74fcd82ca019f8ff5cf9c | null | 1981-01-01T00:05:00 | true | [CH2:1]([S:3][C:4]1[C@:5]2([CH2:22][C@H:21]([OH:23])[C@@:20]3([F:24])[C@@H:10]([CH2:11][CH2:12][C:13]4[C@:18]3([CH3:19])[CH:17]=[CH:16][C:15](=[O:25])[CH:14]=4)[C@@H:7]2[CH2:8][CH:9]=1)[CH3:6])[CH3:2].[Br:26]N1C(=O)CCC1=O>ClCCl>[Br:26][C:9]1[CH2:8][C@H:7]2[C@H:10]3[C@:20]([F:24])([C@@H:21]([OH:23])[CH2:22][C@:5]2([CH3:6])[C:4]=1[S:3][CH2:1][CH3:2])[C@:18]1([CH3:19])[C:13](=[CH:14][C:15](=[O:25])[CH:16]=[CH:17]1)[CH2:12][CH2:11]3 | O=C1CCC(=O)N1Br | CCSC1=CC[C@H]2[C@@H]3CCC4=CC(=O)C=C[C@]4(C)[C@@]3(F)[C@@H](O)C[C@]12C | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | 25 | 2 | A solution of (11β)-17-(ethylthio)-9-fluoro-11-hydroxyandrosta-1,4,16-trien-3-one (181 mg) in dichloromethane (10 ml) containing N-bromosuccinimide (98 mg) is stirred at room temperature for 2 hours and the reaction mixture is subjected to preparative thin layer chromatography on silica gel plates to isolate the title compound. | CCSC1=C(Br)C[C@H]2[C@@H]3CCC4=CC(=O)C=C[C@]4(C)[C@@]3(F)[C@@H](O)C[C@]12C | null | null | null |
1,138,984 | ord_dataset-68715347640045adb1b09e6a04722b0e | null | 2012-01-01T00:03:00 | true | [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C@H:11]2[CH2:16][CH2:15][CH2:14][CH2:13][NH:12]2)=[O:10])=[CH:4][C:3]=1[N+:17]([O-:19])=[O:18].C=O.[C:22]([BH3-])#N.[Na+].O>CO>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C@H:11]2[CH2:16][CH2:15][CH2:14][CH2:13][N:12]2[CH3:22])=[O:10])=[CH:4][C:3]=1[N+:17]([O-:19])=[O:18] | Nc1ccc(NC(=O)[C@H]2CCCCN2)cc1[N+](=O)[O-] | [BH3-]C#N | null | C=O | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | O | null | null | null | null | null | null | null | null | null | 25 | 1.17 | (R)—N-(4-Amino-3-nitrophenyl)piperidine-2-carboxamide (2.09 g, 7.9 mmol) was dissolved in MeOH (50 mL), and paraformaldehyde (0.95 g) and sodium cyanoborohydride (0.50 g, 8.0 mmol) were added. The mixture was stirred at room temperature for 70 min, and water added dropwise. The solvent was evaporated and the residue partitioned between water and EA (150 mL each). The phases were separated and the aqueous phase extracted with EA (2×100 mL). The combined EA layers were washed with brine, dried over magnesium sulfate, and concentrated to give (R)—N-(4-amino-3-nitrophenyl)-1-methylpiperidine-2-carboxamide as an orange foam (2.17 g), which was used without purification. | CN1CCCC[C@@H]1C(=O)Nc1ccc(N)c([N+](=O)[O-])c1 | null | 98.7 | null |
1,488,733 | ord_dataset-c3c1091f873b4f40827973a6f1f9b685 | null | 2014-01-01T00:09:00 | true | Cl[C:2]1[N:6]([CH2:7][O:8][CH2:9][CH2:10][Si:11]([CH3:14])([CH3:13])[CH3:12])[C:5]2[CH:15]=[CH:16][CH:17]=[CH:18][C:4]=2[N:3]=1.[OH:19][C:20]1[CH:25]=[CH:24][C:23]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[CH:22][CH:21]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[CH3:12][Si:11]([CH3:14])([CH3:13])[CH2:10][CH2:9][O:8][CH2:7][N:6]1[C:5]2[CH:15]=[CH:16][CH:17]=[CH:18][C:4]=2[N:3]=[C:2]1[O:19][C:20]1[CH:21]=[CH:22][C:23]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:31])([CH3:30])[CH3:32])=[CH:24][CH:25]=1 | C[Si](C)(C)CCOCn1c(Cl)nc2ccccc21 | CC(C)(C)OC(=O)Nc1ccc(O)cc1 | null | O=C([O-])[O-] | [Cs+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | 60 | 24 | A mixture of 2-chloro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazole (8.7 g), tert-butyl 4-hydroxyphenylcarbamate (6.4 g) and cesium carbonate (20 g) in DMF (60 mL) was stirred at 60° C. for 24 h. After cooling to room temperature, to the mixture was added SiO2, the mixture was evaporated, and then the residue was purified by column chromatography (silica gel, eluted with 0%-50% EtOAc in hexane) to give tert-butyl {4-[(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazol-2-yl)oxy]phenyl}carbamate (14 g) as brown oil. | CC(C)(C)OC(=O)Nc1ccc(Oc2nc3ccccc3n2COCC[Si](C)(C)C)cc1 | null | 100.5 | null |
1,170,581 | ord_dataset-d24cc23b3db94284bb83a2ccdd9eb880 | null | 2012-01-01T00:05:00 | true | [C@H:1]1([NH:10][C:11]2[CH:20]=[CH:19][C:18]3[C:13](=[CH:14][CH:15]=[C:16]([NH2:21])[CH:17]=3)[N:12]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.C(O)(=O)C.[C:26]([O:30][C:31](=[O:37])[N:32]([CH3:36])[CH2:33][CH:34]=O)([CH3:29])([CH3:28])[CH3:27].C([BH3-])#N.[Na+].C([O-])(O)=O.[Na+]>CO>[C:26]([O:30][C:31](=[O:37])[N:32]([CH2:33][CH2:34][NH:21][C:16]1[CH:17]=[C:18]2[C:13](=[CH:14][CH:15]=1)[N:12]=[C:11]([NH:10][C@H:1]1[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[CH2:3][CH2:2]1)[CH:20]=[CH:19]2)[CH3:36])([CH3:29])([CH3:28])[CH3:27] | Nc1ccc2nc(N[C@@H]3CCc4ccccc43)ccc2c1 | CN(CC=O)C(=O)OC(C)(C)C | null | O=C([O-])O | [BH3-]C#N | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | CC(=O)O | null | null | null | null | null | null | null | null | null | 23 | 1 | A mixture of (R)—N2-indan-1-yl-quinoline-2,6-diamine (453 mg, 1.645 mmol) in Methanol (10 mL) with acetic acid (0.3 mL, 4.935 mmol) and commercially available methyl-(2-oxo-ethyl)carbamic acid tert-butyl ester (300 mg, 1.731 mmol) was stirred at 23° C. for 1 h. Portionwise addition of sodium cyanoborohydride (286 mg, 4.11 mmol) was followed by additional stirring at 23° C. for 3 h. Poured onto saturated NaHCO3-solution and extracted twice with ethyl acetate, dried over Na2SO4 and evaporated totally gave a crude product which was purified by flash chromatography with heptane and ethyl acetate to give the title compound as a yellow foam (550 mg, 73%); MS: m/e=433.4 (M+H+). | CN(CCNc1ccc2nc(N[C@@H]3CCc4ccccc43)ccc2c1)C(=O)OC(C)(C)C | null | 77.3 | null |
1,390,024 | ord_dataset-31641fb65b34430fa7435229b949b604 | null | 2014-01-01T00:01:00 | true | C([O:3][C:4]([C@@H:6]1[CH2:8][C@H:7]1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:5])C.[Li+].[OH-]>CCO>[C:9]1([C@@H:7]2[CH2:8][C@H:6]2[C:4]([OH:5])=[O:3])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1 | CCOC(=O)[C@@H]1C[C@H]1c1ccccc1 | null | null | [Li+] | [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 stirred mixture of 33 (153 g, 804.25 mmol, 1.00 equiv) in EtOH (1 L) was added 1M aq. LiOH (1 L), and the resultant solution was stirred at reflux for 1 h. Volatile solvent was removed under reduced pressure and the residue diluted with EtOAc (1.5 L). The organic phase was washed with water (3×1 L) and brine (1×1 L), dried (Na2SO4), filtered and concentrated in vacuo to afford 117.5 g (90%) of trans-2-phenylcyclopropane-1-carboxylic acid (35) as a white solid. | O=C(O)[C@@H]1C[C@H]1c1ccccc1 | null | 90.1 | null |
1,577,133 | ord_dataset-9741bb5fd93044078df2a45f45733054 | null | 2015-01-01T00:04:00 | true | [CH3:1][C:2]1[C:10]2[CH2:9][O:8][C:7](=[O:11])[C:6]=2[CH:5]=[CH:4][C:3]=1[CH:12]1[CH2:14][O:13]1.[CH3:15][CH:16]1[CH2:21][NH:20][CH2:19][CH2:18][NH:17]1>CS(C)=O.O>[CH3:15][CH:16]1[CH2:21][N:20]([CH2:14][CH:12]([C:3]2[CH:4]=[CH:5][C:6]3[C:7](=[O:11])[O:8][CH2:9][C:10]=3[C:2]=2[CH3:1])[OH:13])[CH2:19][CH2:18][N:17]1[CH2:14][CH:12]([C:3]1[CH:4]=[CH:5][C:6]2[C:7](=[O:11])[O:8][CH2:9][C:10]=2[C:2]=1[CH3:1])[OH:13] | CC1CNCCN1 | Cc1c(C2CO2)ccc2c1COC2=O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CS(C)=O | O | null | null | null | null | null | null | null | null | null | 150 | null | A mixture of 4-methyl-5-oxiran-2-yl-2-benzofuran-1(3H)-one (700 mg, 3.684 mmol) and 2-methylpiperazine (184 mg, 1.842 mmol) in 2 mL DMSO was heated under microwave condition (150° C.) for 1 hr. After cooling to rt., the mixture was diluted with water (50 mL), extracted with EtOAc (3×50 mL). The combined organic layers were washed with brine and dried over Na2SO4, then concentrated. The residue was purified by prep-HPLC to obtain two peaks (peak 1 and peak 2). Each peak was further separated by SFC chiral chromatography to obtain three chiral isomers for each (of 8 isomers six were obtained, though two may be mixtures of 2 isomers). | Cc1c(C(O)CN2CCN(CC(O)c3ccc4c(c3C)COC4=O)C(C)C2)ccc2c1COC2=O | null | null | null |
930,380 | ord_dataset-d8a5dc784dde4465894ec7c69d2e3ba6 | null | 2010-01-01T00:01:00 | true | C([NH:5][S:6]([C:9]1[CH:10]=[C:11]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]3[N:26]=[C:25]([C:27]4[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:35])[F:34])=[C:29]([F:37])[CH:28]=4)[CH:24]=[C:23]([C:38]([F:41])([F:40])[F:39])[N:22]=3)[CH:16]=2)[CH:12]=[CH:13][CH:14]=1)(=[O:8])=[O:7])(C)(C)C.C(O)(C(F)(F)F)=O>ClCCl>[F:37][C:29]1[CH:28]=[C:27]([C:25]2[CH:24]=[C:23]([C:38]([F:39])([F:41])[F:40])[N:22]=[C:21]([C:17]3[CH:16]=[C:15]([C:11]4[CH:12]=[CH:13][CH:14]=[C:9]([S:6]([NH2:5])(=[O:8])=[O:7])[CH:10]=4)[CH:20]=[CH:19][CH:18]=3)[N:26]=2)[CH:32]=[CH:31][C:30]=1[C:33]([F:34])([F:36])[F:35] | CC(C)(C)NS(=O)(=O)c1cccc(-c2cccc(-c3nc(-c4ccc(C(F)(F)F)c(F)c4)cc(C(F)(F)F)n3)c2)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | O=C(O)C(F)(F)F | null | null | null | null | null | null | null | null | null | 25 | 15 | To a cooled and stirred solution of 3′-[4-(3-fluoro-4-trifluoromethyl-phenyl)-6-trifluoromethyl-pyrimidin-2-yl]-biphenyl-3-sulfonic acid tert-butylamide (0.47 g) in dichloromethane (6 ml) was added TFA (6 ml) and the reaction mixture was allowed to stir at room temperature for 15 h. The mixture was evaporated to dryness, poured into 2N Na2CO3 solution (25 ml) and extracted with ethyl acetate (3×50 ml). The combined organic layers were washed with brine (50 ml), dried (MgSO4) and evaporated. Further purification by crystallization (ethyl acetate/heptane) yielded the title compound as a white solid (0.27 g, 50%). MS (ISP) 542.1 [(M+H)+]; mp 227.5° C. | NS(=O)(=O)c1cccc(-c2cccc(-c3nc(-c4ccc(C(F)(F)F)c(F)c4)cc(C(F)(F)F)n3)c2)c1 | null | 63.4 | null |
656,209 | ord_dataset-f5d908a6dcb44353a706166b5e9f7f88 | null | 2004-01-01T00:12:00 | true | [C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2(O)[CH2:14][N:13]([CH:15]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH2:12]2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].CS([Cl:33])(=O)=O>ClCCl>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2([Cl:33])[CH2:14][N:13]([CH:15]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH2:12]2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2] | CS(=O)(=O)Cl | CC(C)(C)c1ccc(C2(O)CN(C(c3ccccc3)c3ccccc3)C2)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | null | 18 | To a stirred solution of compound (9) (6.23 g) and N,Ndiisopropylethylamine (3.5 mL) in dichloromethane (100 mL) at 0° C. was added, dropwise, methanesulfonyl chloride (1.4 mL). The mixture was stired at 0° C. for 18 hrs, then washed (water, brine), dried (Na2SO4) and concentrated in vacuo. The crude product was recrystallised from hexane to give 3-(4-tert-butylphenyl)-3-chloro-1-(diphenylmethyl)azetidine (10) (4.73 g) m.p. 145° C. (hexane). Found: C, 80.30; H, 7.05; N, 3.64. C26H28CIN requires C, 80.08; H. 7.24; N, 3.59%. | CC(C)(C)c1ccc(C2(Cl)CN(C(c3ccccc3)c3ccccc3)C2)cc1 | null | null | null |
900,868 | ord_dataset-de6bce51790e4004a27e1a8f2bcc7ded | null | 2009-01-01T00:08:00 | true | Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][CH2:9][CH3:10])[CH:3]=1.[Li]CCCC.C[O:17][B:18](OC)[O:19]C>C1COCC1>[CH2:8]([C:4]1[CH:3]=[C:2]([B:18]([OH:19])[OH:17])[CH:7]=[CH:6][CH:5]=1)[CH2:9][CH3:10] | COB(OC)OC | CCCc1cccc(Br)c1 | null | [Li]CCCC | 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 | -78 | 0.08 | To a solution of Intermediate 214.1 (130 mg, 0.65 mmol) in 4 mL THF at −78° C., was added BuLi (1.4 M in hexanes, 0.557 mL, 0.78 mmol). The mixture was stirred 5 min at −78° C., then trimethylborate (0.109 mL, 0.975 mmol) was added. The reaction was stirred at −78° C. for 10 min, then was removed from the cooling bath and stirred 1 h. The reaction was quenched with 1 N HCl, then was diluted with EtOAc. The organic phase was washed with 1N HCl and brine, dried (Na2SO4) and concentrated to afford 83 mg of Intermediate 214.2 as a colorless oil, which was used without further purification in the following step. | CCCc1cccc(B(O)O)c1 | null | 77.9 | null |
361,027 | ord_dataset-0b24d1f58a024ed7bc2bda95b2430c72 | null | 1997-01-01T00:04:00 | true | [Br:1][CH:2]1[CH2:8][CH:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:6]2[CH:15]=[CH:16][C:17]([CH3:19])=[CH:18][C:5]=2[NH:4][C:3]1=[O:20].[CH3:21][C:22]1([NH:28][C:29](=[O:32])[CH2:30]I)[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1>>[CH3:21][C:22]1([NH:28][C:29](=[O:32])[CH2:30][N:4]2[C:5]3[CH:18]=[C:17]([CH3:19])[CH:16]=[CH:15][C:6]=3[CH:7]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)[CH2:8][CH:2]([Br:1])[C:3]2=[O:20])[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1 | Cc1ccc2c(c1)NC(=O)C(Br)CC2c1ccccc1 | CC1(NC(=O)CI)CCCCC1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Prepared as in Example 20I from 3-bromo-5-phenyl-8-methyl-2,3,4,5-tetrahydro-1H-(1)benzazepin-2-one using N-(1-methylcyclohexyl)-iodoacetamide, M.P. x° C., x% yield for the trans isomer. | Cc1ccc2c(c1)N(CC(=O)NC1(C)CCCCC1)C(=O)C(Br)CC2c1ccccc1 | null | null | null |
1,421,611 | ord_dataset-f8e6e6a2d2bf4135b9e346456c81700f | null | 2014-01-01T00:04:00 | true | Cl[C:2]1[CH:11]=[C:10]([CH3:12])[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[NH2:13][NH2:14]>>[NH:13]([C:2]1[CH:11]=[C:10]([CH3:12])[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1)[NH2:14] | NN | Cc1cc(Cl)nc2ncccc12 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | 25 | null | A solution of 2-chloro-4-methyl-1,8-naphthyridine (330 mg, 1.8 mmol) in NH2NH2 was refluxed at 130° C. for 2 hours. The reaction mixture was cooled to room temperature, then excess NH2NH2 was removed on the rotary evaporator. The residue was taken up in 20 mL of CH2Cl2. The mixture was washed with saturated NaHCO3 (3×15 mL), brine (lx 20 mL), and then dried over MgSO4 and concentrated. The residue was washed with hexane to give 2-hydrazinyl-4-methyl-1,8-naphthyridine. Spectroscopic data: 1H NMR (300 MHz, CDCl3) δ ppm 2.56 (s, 3 H) 6.66 (s, 1 H) 7.22 (dd, J=7.91, 4.40 Hz, 1 H) 8.11 (dd, J=8.06, 1.90 Hz, 1 H) 8.82 (dd, 1 H). | Cc1cc(NN)nc2ncccc12 | null | null | null |
1,476,149 | ord_dataset-c3c1091f873b4f40827973a6f1f9b685 | null | 2014-01-01T00:09:00 | true | [NH2:1][C:2]1[C:3]([C:13]([O:15]C)=[O:14])=[N:4][C:5]([C:8]2[S:9][CH:10]=[CH:11][N:12]=2)=[CH:6][CH:7]=1.[Li+].[OH-].Cl>C1COCC1>[NH2:1][C:2]1[C:3]([C:13]([OH:15])=[O:14])=[N:4][C:5]([C:8]2[S:9][CH:10]=[CH:11][N:12]=2)=[CH:6][CH:7]=1 | COC(=O)c1nc(-c2nccs2)ccc1N | null | null | Cl | [Li+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | 60 | 4 | To a solution of methyl 3-amino-6-(thiazol-2-yl)picolinate (1.0 equiv) in THF (0.5M), was added 1M LiOH (4.0 equiv). After stirring for 4 hours at 60° C., 1 N HCl (4.0 equiv.) was added and the THF was removed in vacuo. The resulting solid was filtered and rinsed with cold H2O (3×20 mL) to yield 3-amino-6-(thiazol-2-yl)picolinic acid (61%). LCMS (m/z): 222.1 (MH+); LC Rt=1.9 min. | Nc1ccc(-c2nccs2)nc1C(=O)O | null | 61 | null |
1,333,889 | ord_dataset-08852243bba44cb28769a5833f1515fe | null | 2013-01-01T00:09:00 | true | [CH3:1][C:2]([CH3:18])([CH3:17])[CH2:3][N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:15]=[CH:14][C:13]([NH2:16])=[CH:12][CH:11]=2)[CH2:6][CH2:5]1.C(N(CC)CC)C.[O:26]=[C:27]([C:31]1[N:39]2[C:34]([CH2:35][CH2:36][CH2:37][CH2:38]2)=[CH:33][C:32]=1[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[C:28](Cl)=[O:29]>C(Cl)Cl>[CH3:1][C:2]([CH3:18])([CH3:17])[CH2:3][N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:15]=[CH:14][C:13]([NH:16][C:28](=[O:29])[C:27](=[O:26])[C:31]3[N:39]4[C:34]([CH2:35][CH2:36][CH2:37][CH2:38]4)=[CH:33][C:32]=3[C:40]3[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=3)=[CH:12][CH:11]=2)[CH2:6][CH2:5]1 | O=C(Cl)C(=O)c1c(-c2ccccc2)cc2n1CCCC2 | CC(C)(C)CN1CCN(c2ccc(N)cc2)CC1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | CCN(CC)CC | null | null | null | null | null | null | null | null | null | 25 | 0.5 | To an ice-cold solution of 4-[4-(2,2-dimethyl-propyl)-piperazin-1-yl]-phenylamine (prepared as described in Reference Example 93, 300 mg, 1.21 mmol) and triethylamine (0.33 mL, 2.4 mmol) in dry DCM (12 mL) was added a solution of oxo-(2-phenyl-5,6,7,8-tetrahydro-indolizin-3-yl)-acetyl chloride (prepared as described in Reference Example 21, 407 mg, 1.41 mmol) in DCM (5 mL). The mixture was warmed to room temperature and stirred for 30 min then diluted with DCM, washed successively with water, sodium bicarbonate solution and brine, then dried over sodium sulfate. Concentration gave a residue which was purified by preparative TLC using ethyl acetate and hexane (3:7) as eluent to afford N-{4-[4-(2,2-dimethyl-propyl)-piperazin-1-yl]-phenyl}-2-oxo-2-(2-phenyl-5,6,7,8-tetrahydro-indolizin-3-yl)-acetamide (220 mg, 36%) as a yellow powder. | CC(C)(C)CN1CCN(c2ccc(NC(=O)C(=O)c3c(-c4ccccc4)cc4n3CCCC4)cc2)CC1 | null | 36.5 | null |
623,825 | ord_dataset-c9f990dde2dc45d0948ecbe037a0d819 | null | 2004-01-01T00:01:00 | true | [Br:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][C:7]2[O:8][C:9]([CH3:28])=[C:10]([CH3:27])[C:11]=2[C:12]([C:14]2[CH:19]=[C:18]([CH:20]([CH3:22])[CH3:21])[C:17]([OH:23])=[C:16]([CH:24]([CH3:26])[CH3:25])[CH:15]=2)=[O:13])=[CH:4][CH:3]=1.Cl[S:32]([C:35]1[CH:43]=[CH:42][C:38]([C:39]([OH:41])=[O:40])=[C:37]([OH:44])[CH:36]=1)(=[O:34])=[O:33]>>[Br:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][C:7]2[O:8][C:9]([CH3:28])=[C:10]([CH3:27])[C:11]=2[C:12]([C:14]2[CH:19]=[C:18]([CH:20]([CH3:22])[CH3:21])[C:17]([O:23][S:32]([C:35]3[CH:43]=[CH:42][C:38]([C:39]([OH:41])=[O:40])=[C:37]([OH:44])[CH:36]=3)(=[O:34])=[O:33])=[C:16]([CH:24]([CH3:25])[CH3:26])[CH:15]=2)=[O:13])=[CH:4][CH:3]=1 | Cc1oc(Cc2ccc(Br)cc2)c(C(=O)c2cc(C(C)C)c(O)c(C(C)C)c2)c1C | O=C(O)c1ccc(S(=O)(=O)Cl)cc1O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The title compound was prepared according to the procedure in Example 4 using [2-(4-bromo-benzyl)-4,5-dimethyl-furan-3-yl]-(3,5-diisopropyl-4-hydroxy-phenyl)-methanone (1.30 g, 2.77 mmol) and 4-chlorosulphonyl-2-hydroxybenzoic acid (1.00 g, 4.22 mmol). Purification on Dynamax C18 (90% CH3CN/H20) gave 0.98 g (53%) of the title compound as an off white solid, mp 165-168° C. 1H NMR (DMSO-d6) δ1.05 (d, 12 H), 1.80 (s, 3 H), 2.19 (s, 3 H), 3.06 (septet, 2 H), 3.81 (s, 2 H), 6.92 (d 2 H), 7.39 (dd, 2 H), 7.44 (s, 1 H), 7.45 (s, 2 H), 7.48 (d, 1 H), 8.05 (d, 1 H). IR (KBr) 3400, 2950, 1680, 1375 and 1190 cm−1. mass spectrum (−ESI) m/z 667 (M−H). Anal. Calcd. for C33H33BrO8S: C, 59.20; H, 4.97; N, 0.00. Found: C, 59.18; H, 5.21; N, 0.08. | Cc1oc(Cc2ccc(Br)cc2)c(C(=O)c2cc(C(C)C)c(OS(=O)(=O)c3ccc(C(=O)O)c(O)c3)c(C(C)C)c2)c1C | null | 52.8 | null |
1,305,166 | ord_dataset-78c3f723155a4347a902b53bcee1524d | null | 2013-01-01T00:06:00 | true | [C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([NH2:33])[C:18]([NH:19][CH:20]4[CH2:25][CH2:24][N:23]([CH2:26][C:27]5[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=5)[CH2:22][CH2:21]4)=[C:13]3[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.[Cl:41][CH2:42][C:43](Cl)=[O:44]>C(Cl)Cl>[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([NH:33][C:43](=[O:44])[CH2:42][Cl:41])[C:18]([NH:19][CH:20]4[CH2:25][CH2:24][N:23]([CH2:26][C:27]5[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=5)[CH2:22][CH2:21]4)=[C:13]3[CH:12]=[CH:11]2)(=[O:8])=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1 | O=C(Cl)CCl | Nc1cnc2c(ccn2S(=O)(=O)c2ccccc2)c1NC1CCN(Cc2ccccc2)CC1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | CCN(CC)CC | null | null | null | null | null | null | null | null | null | 0 | 2 | To an ice-cold mixture of 1-benzenesulfonyl-N*4*-(1-benzyl-piperidin-4-yl)-1H-pyrrolo[2,3-b]pyridine-4,5-diamine 1.30 g, 2.80 mmol) and triethylamine (0.59 mL, 4.20 mmol) in DCM (50 mL) was added chloroacetyl chloride (0.25 mL, 3.10 mmol) and the mixture was stirred 2 h. The reaction mixture was diluted with DCM, washed with water, brine, and dried over sodium sulphate. The residue was purified by flash (silica gel. 0-5% MeOH/DCM) to afford N-[1-Benzenesulfonyl-4-(1-benzyl-piperidin-4-ylamino)-1H-pyrrolo[2,3-b]pyridin-5-yl]-2-chloro-acetamide (1.10 g, 72%): LCMS (method E, ESI): RT=1.2 min; m+1=538.2. | O=C(CCl)Nc1cnc2c(ccn2S(=O)(=O)c2ccccc2)c1NC1CCN(Cc2ccccc2)CC1 | null | 73 | null |
1,184,105 | ord_dataset-9cd817a75dfc4fe7ad19d4232772d5ff | null | 2012-01-01T00:07:00 | true | C[O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][C:7]([N+:13]([O-:15])=[O:14])=[CH:6]2.[OH-].[Na+]>Br>[OH:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][C:7]([N+:13]([O-:15])=[O:14])=[CH:6]2 | COc1ccc2ncc([N+](=O)[O-])cc2c1 | null | null | Br | [Na+] | [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 | 120 | 16 | 6-Methoxy-3-nitroquinoline (Magnus, P. et al., J. Am. Chem. Soc. 119, 5591, 1997; 100 mg, 0.49 mmol) was dissolved in hydrogen bromide solution (47% aq, 2.5 mL, 0.2 M), heated and stirred at 120° C. for 16 hours. The reaction mixture was cooled to room temperature, neutralized with 6N NaOH, then extracted with EtOAc (150 mL). The organic layer was dried over Na2SO4 and purified by flash chromatography (SiO2, 40-50% EtOAc/hexanes), obtaining 73 mg (78%) of 6-hydroxy-3-nitroquinoline. LC/MS (m/z): 190.9 (MH+), Rt 1.97 minutes. | O=[N+]([O-])c1cnc2ccc(O)cc2c1 | null | 78.3 | null |
412,751 | ord_dataset-fbdd058349aa456f812e3546c84baab5 | null | 1998-01-01T00:09:00 | true | C([S:4][CH2:5][CH:6]([CH2:10][C:11]([OH:13])=[O:12])[C:7]([OH:9])=[O:8])(=O)C.[OH-].[Na+]>O>[SH:4][CH2:5][CH:6]([CH2:10][C:11]([OH:13])=[O:12])[C:7]([OH:9])=[O:8] | CC(=O)SCC(CC(=O)O)C(=O)O | null | null | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | null | null | null | null | null | null | null | null | null | null | 25 | 15 | 582 g (2.85 mol) of acetylthiomethylbutanedioic acid (VII) are added, under nitrogen and while cooling with ice, to a solution of 570 g (14.25 mol) of NaOH in 3 litres of water (exothermic reaction). After 15 hours' stirring at room temperature, the reaction mixture is acidified to pH 1 with concentrated hydrochloric acid and extraction is carried out with ether. The combined organic phases are dried over sodium sulfate and concentrated to dryness, and the crystalline residue is washed with 200 ml of cold dichloromethane. There are obtained 385 g of crystals having a melting point of 107°-108.5° C. | O=C(O)CC(CS)C(=O)O | null | 82.3 | null |
1,752,016 | ord_dataset-97eb2ab57fec4160922caae33b54d956 | null | 2016-01-01T00:08:00 | true | [Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]([F:12])([F:11])[F:10])[CH:5]=[CH:4][C:3]=1[NH:13][C:14]([C:16]1[CH:21]=[CH:20][C:19]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:18][N:17]=1)=O.P(Cl)(Cl)(Cl)(Cl)[Cl:27]>C1C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]([F:12])([F:11])[F:10])[CH:5]=[CH:4][C:3]=1[N:13]=[C:14]([Cl:27])[C:16]1[CH:21]=[CH:20][C:19]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:18][N:17]=1 | ClP(Cl)(Cl)(Cl)Cl | CS(=O)(=O)c1ccc(C(=O)Nc2ccc(OC(F)(F)F)cc2Cl)nc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | c1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | null | 5-Methanesulfonyl-pyridine-2-carboxylic acid (2-chloro-4-trifluoromethoxy-phenyl)-amide 7 (1.1 g, 2.79 mmol) in benzene (20 mL) was added to PCl5 (1.26 g, 6.0 mmol) and the mixture was heated to reflux overnight. The solvent was removed and the residue was further dried under high vacuum. Crude N-(2-chloro-4-trifluoromethoxyphenyl)-5-(methylsulfonyl)picolinimidoyl chloride was obtained as a yellow solid (1.60 g). The N-(2-chlor-4-trifluoromethoxyophenyl)-5-(methylsulfonyl)picolinimidoyl chloride was dissolved into anhydrous THF (30 mL) and the reaction was cooled down to 0° C. and hydrazine monohydrate (9.0 mL) was added. The reaction was kept at 0° C. for 10 min and warmed to ambient temperature in 0.5 h. The solvent was removed and the residue was purified by column chromatography (eluting with hexane and ethyl acetate 1:1) to give N′-(2-chloro-4-trifluoromethoxyphenyl)-5-(methylsulfonyl)picolinimidohydrazide 8 as a yellow solid. Yield: 0.56 g, 50%. | CS(=O)(=O)c1ccc(C(Cl)=Nc2ccc(OC(F)(F)F)cc2Cl)nc1 | null | null | null |
936,911 | ord_dataset-90b0aa1f83334a02919b2be3a1c04542 | null | 2010-01-01T00:02:00 | true | [Br:1][C:2]1[CH:3]=[N:4][C:5](Cl)=[N:6][CH:7]=1.[CH3:9][O:10][C:11]1[CH:18]=[CH:17][C:14]([CH2:15][NH2:16])=[CH:13][CH:12]=1>>[Br:1][C:2]1[CH:3]=[N:4][C:5]([NH:16][CH2:15][C:14]2[CH:17]=[CH:18][C:11]([O:10][CH3:9])=[CH:12][CH:13]=2)=[N:6][CH:7]=1 | Clc1ncc(Br)cn1 | COc1ccc(CN)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 | 2 | 5-Bromo-2-chloropyrimidine (300 mg, 1.55 mmol) was dissolved by heating at 120° C. in 4-methoxybenzylamine (2.10 g, 15.4 mmol), and the solution was stirred at the same temperature for 2 hours. The reaction mixture was directly subjected to silica gel column chromatography (hexane:ethyl acetate=30:1→5:1) for purification to obtain 5-bromo-N-(4-methoxybenzyl)pyrimidin-2-amine (445 mg, 98%) as a colorless amorphous solid. | COc1ccc(CNc2ncc(Br)cn2)cc1 | null | 97.6 | null |
587,430 | ord_dataset-cb5dd7a8b94e4f19a9148a1904b0dcb6 | null | 2003-01-01T00:03:00 | true | [CH:1]1([CH2:6][CH2:7][C:8]2[N:16]([C:17]3[CH:25]=[CH:24][C:20]([CH2:21][CH2:22][NH2:23])=[CH:19][CH:18]=3)[C:11]3=[N:12][CH:13]=[CH:14][CH:15]=[C:10]3[N:9]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[O:26]1[CH2:28][C@H:27]1[CH2:29][O:30][C:31]1[C:39]2[NH:38][C:37](=[O:40])[NH:36][C:35]=2[CH:34]=[CH:33][CH:32]=1>C(Cl)(Cl)Cl.CO>[CH:1]1([CH2:6][CH2:7][C:8]2[N:16]([C:17]3[CH:25]=[CH:24][C:20]([CH2:21][CH2:22][NH:23][CH2:28][CH:27]([OH:26])[CH2:29][O:30][C:31]4[C:39]5[NH:38][C:37](=[O:40])[NH:36][C:35]=5[CH:34]=[CH:33][CH:32]=4)=[CH:19][CH:18]=3)[C:11]3=[N:12][CH:13]=[CH:14][CH:15]=[C:10]3[N:9]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1 | NCCc1ccc(-n2c(CCC3CCCC3)nc3cccnc32)cc1 | O=c1[nH]c2cccc(OC[C@@H]3CO3)c2[nH]1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | ClC(Cl)Cl | null | null | null | null | null | null | null | null | null | null | null | 4-[2-(2-Cyclopentylethyl)-3H-imidazo[4,5-b]pyridin-3-yl]phenethylamine (0.229 g, 0.68 mmol) was reacted with 4-[(2S)oxiranylmethoxy]-1,3-dihydro-2H-benzimidazol-2-one (0.141 g, 0.68 mmol) according to Procedure G (eluant: 20:1 going to 5:1 chloroform-methanol containing 1% ammonium hydroxide) to give the title compound (0.032 g, 0.059 mmol). | O=c1[nH]c2cccc(OCC(O)CNCCc3ccc(-n4c(CCC5CCCC5)nc5cccnc54)cc3)c2[nH]1 | null | 8.7 | null |
291,797 | ord_dataset-6c3ec086c8c9475e8d31a44641b49e02 | null | 1994-01-01T00:06:00 | true | [CH:1]1([CH2:4][N:5]2[C:14](=[O:15])[C:13]3[N:12](CCC(=O)C)[CH:11]=[N:10][C:9]=3[N:8]([CH2:21][CH:22]3[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]3)[C:6]2=[O:7])[CH2:3][CH2:2]1.[OH-].[K+]>C(O)C>[CH:1]1([CH2:4][N:5]2[C:14](=[O:15])[C:13]3[NH:12][CH:11]=[N:10][C:9]=3[N:8]([CH2:21][CH:22]3[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]3)[C:6]2=[O:7])[CH2:3][CH2:2]1 | CC(=O)CCn1cnc2c1c(=O)n(CC1CC1)c(=O)n2CC1CCCCC1 | null | null | [K+] | [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 | This was prepared from the compound of Example 21, 900 mg, by treating with 200 mg potassium hydroxide in 10 ml of ethanol for 1 hour at room temperature. The title compound was isolated in an analogous manner to Example 18, m.p. 181° C. | O=c1c2[nH]cnc2n(CC2CCCCC2)c(=O)n1CC1CC1 | null | null | null |
1,193,241 | ord_dataset-4e81c470cc3b429faf5e1caa50f70a98 | null | 2012-01-01T00:08:00 | true | [CH3:1][O:2][C:3](=[O:21])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][C:12]2[CH:17]=[CH:16][C:15]([Br:18])=[CH:14][C:13]=2[CH2:19]Br)[CH:6]=1.[Cl:22][C:23]1[CH:36]=[CH:35][C:26]([O:27][C@H:28]2[O:32][C:31](=[O:33])[NH:30][C@@H:29]2[CH3:34])=[CH:25][CH:24]=1>>[CH3:1][O:2][C:3](=[O:21])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][C:12]2[CH:17]=[CH:16][C:15]([Br:18])=[CH:14][C:13]=2[CH2:19][N:30]2[C@H:29]([CH3:34])[C@@H:28]([O:27][C:26]3[CH:35]=[CH:36][C:23]([Cl:22])=[CH:24][CH:25]=3)[O:32][C:31]2=[O:33])[CH:6]=1 | COC(=O)Cc1cccc(Oc2ccc(Br)cc2CBr)c1 | C[C@H]1NC(=O)O[C@@H]1Oc1ccc(Cl)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Prepared according to the procedure described in Example 6, Step 5, using the following starting materials: [3-(4-bromo-2-bromomethyl-phenoxy)-phenyl]-acetic acid methyl ester and (4R,5S)-5-(4-chloro-phenoxy)-4-methyl-oxazolidin-2-one. | COC(=O)Cc1cccc(Oc2ccc(Br)cc2CN2C(=O)O[C@H](Oc3ccc(Cl)cc3)[C@H]2C)c1 | null | null | null |
1,113,242 | ord_dataset-375a420ee9b042918ddca20f02df37d3 | null | 2011-01-01T00:11:00 | true | [C:1]([CH2:3][N:4]1[CH2:8][CH2:7][N:6]([CH2:9][C:10]#[N:11])[CH:5]1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)#[N:2].[CH2:18]1[CH2:22]O[CH2:20][CH2:19]1>>[CH:20](=[N:11][CH2:10][CH2:9][N:6]1[CH2:7][CH2:8][N:4]([CH2:3][CH2:1][N:2]=[CH:22][C:18]2[CH:16]=[CH:15][CH:14]=[CH:20][CH:19]=2)[CH:5]1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:19]1[CH:13]=[CH:12][CH:5]=[CH:22][CH:18]=1 | C1CCOC1 | N#CCN1CCN(CC#N)C1c1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | 40 | null | 1 equal mole of (3-cyanomethyl-2-phenyl-imidazolidin-1-yl) -acetonitrile and THF were mixed in a reactor and the reactor was purged with nitrogen gas. The reaction mixture was then transferred to a feeding vessel. The reactor was washed with THF and the solution was added into the mixture in the feeding vessel. 3 equal moles of LiAlH4 in THF solution was added to the reactor. 4 equal moles of methanol and THF were mixed in another feeding vessel, this mixture was added over the next 40 minutes at an internal temperature of 35 to 40° C. into the main reaction mixture. The solution was then heated to an internal temperature of 40° C. under constant stirring for one additional hour. The mixture of methanol and THF was slowly added to the mixture in the feeding vessel at an internal temperature of 39° C.-45° C. The mixture was stirred at an internal temperature of 40° C. for an additional 30 minutes. The mixture was then cooled to an internal temperature of 10° C. within 1 hour. Na2SO4 and NaOH were added to the reaction mixture. Saturated Na2CO3-solution was added at an internal temperature of 10-18° C. via a feeding vessel. The reaction mixture was stirred at an internal temperature of 10° C. overnight. Na2HPO4 was added to the mixture and the reaction suspension was filtered into the stirring vessel. The filter cake was washed with two volumes of THF. The suspension of Na2HPO4 and the filtrate was stirred for one hour in the stirring vessel and then filtered over a nutsch. The filter cake was washed with THF. Both filtrates (filtration and washing) were then transferred into the second reactor (via inline-filter). 2 equal moles of benzaldehyde was added to the filtrate at 20° C. (via inline filter). THF was distilled off at an internal temperature of 10-20° C. and at a pressure of 130-210 mbar, external temperature (ET)=50° C. Hexane was then added (ET=40° C.) to the mixture. Water was then distilled off at an internal temperature of 16-20° C., with a pressure of 170-190 mbar and a AT of 40-43° C. The hexane was further distilled off at an internal temperature of 16° C., at a pressure of 160-180 mbar and ET=44° C. Isopropanol was added to the reactor via a feeding vessel. Isopropanol was distilled off at IT=10-27° C., p=30-114 mbar and ET=50° C. The reaction mixture was stirred for an hour at an internal temperature of 35° C. The reaction mixture was then cooled to −5° C. and stirred overnight. The nutsch was again purged with nitrogen and the suspension was again filtered. The filter cake was washed with cold (6° C.) isopropanol. The product, benzylidene-(2-{3-[2-(benzylidene-amino)-ethyl]-2-phenyl-imidazolidin-1-yl}-ethyl)-amine, was allowed to dry in a PROVATECH dryer at a temperature of 30-40° C. at a pressure of less than or equal to 30 mbar. The reaction was carried out in five independent reaction vessels with the following results: Flask 1 gave benzylidene-(2-{3-[2-(benzylidene-amino)-ethyl]-2-phenyl-imidazolidin-1-yl}-ethyl)-amine as an off-white solid with a purity of 99.93% as measured by gas chromatography, which represented a total yield of 84.85%. Flask 2 gave benzylidene-(2-{3-[2-(benzylidene -amino)-ethyl]-2-phenyl-imidazolidin-1-yl}-ethyl)-amine as an off-white solid with a purity of 99.42% as measured by gas chromatography, which represented a total yield of 77.1%. Flask 3 gave benzylidene-(2-{3-[2-(benzylidene-amino)-ethyl]-2-phenyl -imidazolidin-1-yl}-ethyl)-amine as an off-white solid with a purity of 99.89% as measured by gas chromatography, which represented a total yield of 78.3%. Flask 4 gave benzylidene-(2-{3-[2-(benzylidene-amino) -ethyl]-2-phenyl-imidazolidin-1-yl}-ethyl)-amine as an off-white solid with a purity of 99.87% as measured by gas chromatography, which represented a total yield of 82.7%. | C(=NCCN1CCN(CCN=Cc2ccccc2)C1c1ccccc1)c1ccccc1 | null | 84.85 | null |
936,079 | ord_dataset-90b0aa1f83334a02919b2be3a1c04542 | null | 2010-01-01T00:02:00 | true | [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14](=[O:23])[NH:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[Br:22])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:27][CH:28]1[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1>CN(C)C=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14](=[O:23])[N:15]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[Br:22])[CH2:27][CH:28]2[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3] | BrCC1CCCCC1 | CC(C)(C)OC(=O)N1CCC(C(=O)Nc2ccccc2Br)CC1 | 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 | 0 | 1 | 4-(2-Bromo-phenylcarbamoyl)-piperidine-1-carboxylic acid tert-butyl ester (1.0 g, 2.60 mmol) was dissolved in dry N,N-dimethylformamide (10.0 mL). To the reaction mixture was then added at 0° C. sodium hydride (60% in mineral oil, 127.3 mg, 3.18 mmol) under nitrogen atmosphere and the reaction mixture was stirred at 0° C. for one hour. To the reaction mixture was then added at 0° C., bromomethyl-cyclohexane (0.55 g, 3.13 mmol). The reaction mixture was stirred at 0° C. for one hour, then at room temperature under nitrogen atmosphere for 18 hours. The reaction mixture was then added into an excess of water-ice and a solid precipitated. The solid was filtered by suction, washed with water and dried to yield a crude solid. The crude solid was purified via flash chromatography (25% ethyl acetate/hexanes) to yield the title compound as a solid. | CC(C)(C)OC(=O)N1CCC(C(=O)N(CC2CCCCC2)c2ccccc2Br)CC1 | null | null | null |
1,229,407 | ord_dataset-cde802cdb7434a5f82a22981ccaefc4e | null | 2012-01-01T00:11:00 | true | N[C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[C:11]([O:13][CH3:14])=[O:12])[C:5]([OH:7])=[O:6].N([O-])=O.[Na+].C(OCC)(=O)C.[BrH:25]>C(O)(=O)C.[Cu](Cl)Cl>[Br:25][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[C:11]([O:13][CH3:14])=[O:12])[C:5]([OH:7])=[O:6] | Br | COC(=O)c1ccc(C(=O)O)cc1N | null | Cl[Cu]Cl | O=N[O-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOC(C)=O | CC(=O)O | null | null | null | null | null | null | null | null | null | null | 0.5 | To 3-amino-4-methoxycarbonylbenzoic acid (1.95 g, 10 mmol) suspended in 48% hydrobromic acid (50 mL) and acetic acid (50 mL), an aqueous solution (20 mL) of sodium nitrite (0.69 g, 10 mmol) was added at −10° C., and the resulting solution was stirred for 30 minutes. The solution was added to copper bromide (I) (1.44 g, 10 mmol) in 48% hydrobromic acid (50 mL) at −10° C., and the resulting reaction mixture was stirred at room temperature for 1 hour. After addition of ethyl acetate, the reaction mixture was washed with water, dried over magnesium sulfate, filtered through celite and purified by silica gel column chromatography to give 1.70 g of the desired product as a colorless solid (yield 59%). | COC(=O)c1ccc(C(=O)O)cc1Br | null | 59 | null |
860,384 | ord_dataset-93908aaae836460ebd48d733eccad483 | null | 2009-01-01T00:01:00 | true | Cl[C:2]1[C:3]2[CH:17]=[CH:16][C:15](=[O:18])[N:14]([C:19]3[C:24]([F:25])=[CH:23][CH:22]=[CH:21][C:20]=3[F:26])[C:4]=2[N:5]=[C:6]([NH:8][CH:9]([CH2:12][OH:13])[CH2:10][OH:11])[N:7]=1.CC1(C)C(C)(C)OB([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=2[OH:41])O1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:41][C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=1[C:2]1[C:3]2[CH:17]=[CH:16][C:15](=[O:18])[N:14]([C:19]3[C:24]([F:25])=[CH:23][CH:22]=[CH:21][C:20]=3[F:26])[C:4]=2[N:5]=[C:6]([NH:8][CH:9]([CH2:12][OH:13])[CH2:10][OH:11])[N:7]=1 | O=c1ccc2c(Cl)nc(NC(CO)CO)nc2n1-c1c(F)cccc1F | CC1(C)OB(c2ccccc2O)OC1(C)C | null | c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1 | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1COCCO1 | O | null | null | null | null | null | null | null | null | null | 150 | null | A solution of 4-Chloro-2-(2-hydroxy-1-hydroxymethyl-ethylamino)-8-(2,6-difluoro-phenyl)-8H-pyrido[2,3-d]pyrimidin-7-one (50 mg, 0.13 mmol) in dioxane/H2O (3:1, 4.8 mL) was mixed with 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (44.0 mg, 0.20 mmol) and K2CO3 (71.9 mg, 0.52 mmol). The resultant mixture was bubbled with argon for 5 minutes, and added by Pd(PPh3)4 (3.0 mg, 0.0026 mmol). The reaction tube was sealed and heated with “Smith Creator” (microwave, 150° C.) for 15 minutes. The mixture was concentrated under vaco. Flash chromatography (EtOAc/Hexane, 3:1) then afforded the title compound (82%): MS (ES) m/z 441 (M+H)+; 1H-NMR(CDCl3) δ 1.65 (s, br, 2H), 3.80 (m, br, 5H), 6.05 (m, br, 1H), 6.54 (m, 1H), 7.15 (m, 4H), 7.48 (m, 3H), 7.98 (m, 1H). | O=c1ccc2c(-c3ccccc3O)nc(NC(CO)CO)nc2n1-c1c(F)cccc1F | null | 82 | null |
731,393 | ord_dataset-eb4226b4f7644a01a737e7547b70014a | null | 2006-01-01T00:09:00 | true | [CH2:1]([C:8]1[C:13](I)=[CH:12][CH:11]=[C:10]([N:15]2[CH2:19][C@@H:18]([O:20][CH3:21])[C@H:17]([OH:22])[CH2:16]2)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:23]([C:25]1([N:31]2[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]2)[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1)#[CH:24]>>[CH2:1]([C:8]1[C:13]([C:24]#[C:23][C:25]2([N:31]3[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]3)[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)=[CH:12][CH:11]=[C:10]([N:15]2[CH2:19][C@@H:18]([O:20][CH3:21])[C@H:17]([OH:22])[CH2:16]2)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1 | C#CC1(N2CCCCC2)CCCCC1 | CO[C@@H]1CN(c2ccc(I)c(Cc3ccccc3)n2)C[C@H]1O | null | null | null | null | null | null | null | 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 was synthesized in the same manner as in Example 6 except that 2-benzyl-3-iodo-6-[(3R,4R)-3-hydroxy-4-methoxypyrrolidin-1-yl]pyridine (Production Example 1) and 1-(1-ethynylcyclohexyl)piperidine (Production Example 18) were used. | CO[C@@H]1CN(c2ccc(C#CC3(N4CCCCC4)CCCCC3)c(Cc3ccccc3)n2)C[C@H]1O | null | null | null |
910,366 | ord_dataset-46d216f2c4374ef5b9df90427e2a4cd4 | null | 2009-01-01T00:09:00 | true | [CH2:1]([CH:8]1[NH:13][CH2:12][CH2:11][N:10]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[C:27]([F:30])([F:29])[F:28])=[CH:17][CH:16]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:31][N:32]=[C:33]=[O:34]>ClCCl>[CH3:31][NH:32][C:33]([N:13]1[CH2:12][CH2:11][N:10]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[C:27]([F:30])([F:28])[F:29])=[CH:17][CH:16]=2)[CH2:9][CH:8]1[CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:34] | CN=C=O | FC(F)(F)c1ccccc1-c1ccc(CN2CCNC(Cc3ccccc3)C2)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | 25 | 8 | This compound could be made in the following manner: 100 mg of 3-benzyl-1-(2′-trifluoromethyl-biphenyl-4-ylmethyl)-piperazine would be dissolved in dichloromethane, 1.1 equiv. methylisocyanate would be added. The reaction would be shaken at room temperature overnight. The reaction would be concentrated in vacuo. The residue would be diluted with DCM, washed with 1M aqueous sodium hydroxide solution, then dried over sodium sulfate, filtered and concentrated in vacuo. The crude residue would be purified by column chromatography to afford the title compound as free base. Addition of 1 equiv. of 1M HCl in dioxane and concentratation in vacuo would afford the title compound as hydrochloride salt. | CNC(=O)N1CCN(Cc2ccc(-c3ccccc3C(F)(F)F)cc2)CC1Cc1ccccc1 | null | null | null |
667,435 | ord_dataset-c5ee194443334d3e92aff17e46e33bd1 | null | 2005-01-01T00:04:00 | true | B(Br)(Br)Br.[Cl:5][C:6]1[C:16]([Cl:17])=[C:15]([S:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[O:25]C)[CH:14]=[CH:13][C:7]=1[CH:8]=[CH:9][C:10]([OH:12])=[O:11]>C(Cl)Cl>[OH:25][C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=1[S:18][C:15]1[CH:14]=[CH:13][C:7](/[CH:8]=[CH:9]/[C:10]([OH:12])=[O:11])=[C:6]([Cl:5])[C:16]=1[Cl:17] | COc1ccccc1Sc1ccc(C=CC(=O)O)c(Cl)c1Cl | null | null | BrB(Br)Br | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | null | 2 | Boron tribromide (84 mL of a 1.0M solution in CH2Cl2) was added to a suspension of Example 310C in CH2Cl2 (85 mL) at 0° C. After addition was completed, the ice-water bath was removed, and the homogeneous dark solution was stirred for 2 hours before the mixture was poured into 1 N aqueous HCl (100 mL) and ice (100 g), and extracted with EtOAc (3×100 mL). ). The organic layers were combined, washed with brine (1×50 mL), dried (MgSO4), filtered, and concentrated to a white solid (11.3 g). 1H NMR (DMSO-d6, 300 MHz) δ 10.26 (s, 1H), 7.82 (d, J15.6, 1H), 7.74 (d, J=8.5 Hz, 1H), 7.44 (dt, J=7.8 Hz, J=1.7 Hz, 1H), 7.41 (dd, J=7.4 Hz, J=1.7 Hz, 1H), 7.05 (dd, J=8.4 Hz, J=1.3 Hz, 1H), 6.94 (dt, J=7.8 Hz, J=1.4 Hz, 1H), 6.52 (d, J=8.2 Hz, 1H), 6.50 (d, J=16.0 Hz, 1H); MS (APCI) m/z 339 (M−H)−, 375 (M+Cl)−. | O=C(O)/C=C/c1ccc(Sc2ccccc2O)c(Cl)c1Cl | null | null | null |
1,703,106 | ord_dataset-54347fcace774f89850681d6dec8009f | null | 2016-01-01T00:03:00 | true | [OH-].[Na+].[F:3][C:4]1[CH:5]=[CH:6][C:7]([CH:10]([NH:12]C(=O)C)[CH3:11])=[N:8][CH:9]=1>>[F:3][C:4]1[CH:5]=[CH:6][C:7]([CH:10]([NH2:12])[CH3:11])=[N:8][CH:9]=1 | CC(=O)NC(C)c1ccc(F)cn1 | null | null | [Na+] | [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 | 27.5 | null | A mixture of 5N aqueous NaOH solution (5 mL) and N-(1-(5-fluoropyridin-2-yl)ethyl)acetamide (180 mg, 0.4 mmol) was heated under reflux conditions for 12-16 h. After completion of the reaction, the reaction mixture was cooled to a temperature of 20-35° C. The reaction mixture was extracted with DCM, dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford 45 mg of the title compound as a yellow liquid. | CC(N)c1ccc(F)cn1 | null | 80.3 | null |
1,008,248 | ord_dataset-7448b89163bf426c9d9777809ce24cec | null | 2010-01-01T00:11:00 | true | [O:1]([C:8]1[CH:9]=[C:10]([CH:25]=[CH:26][CH:27]=1)[CH2:11][NH:12][C:13]1[CH:18]=[CH:17][C:16]([C@@H:19]2[CH2:21][C@H:20]2[C:22](O)=[O:23])=[CH:15][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:52][C:53]([F:57])([F:56])[CH2:54][NH2:55]>ClCCl.CN(C=O)C>[O:1]([C:8]1[CH:9]=[C:10]([CH:25]=[CH:26][CH:27]=1)[CH2:11][NH:12][C:13]1[CH:18]=[CH:17][C:16]([C@@H:19]2[CH2:21][C@H:20]2[C:22]([NH:55][CH2:54][C:53]([F:57])([F:56])[F:52])=[O:23])=[CH:15][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1 | NCC(F)(F)F | O=C(O)[C@@H]1C[C@H]1c1ccc(NCc2cccc(Oc3ccccc3)c2)cc1 | null | CN(C)C(On1nnc2cccnc21)=[N+](C)C | F[P-](F)(F)(F)(F)F | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | ClCCl | null | null | null | null | null | null | null | null | null | null | 0.25 | To a mixture of racemic-(trans)-2-{4-[(3-phenoxybenzyl)amino]phenyl}cyclopropanecarboxylic acid (I-2a) (0.15 g, 0.41 mmol) in dichloromethane (3 mL) and DMF (1 mL) was added HATU (0.23 g, 0.62 mmol). The mixture was stirred for 15 mins followed by addition of 2,2,2-trifluoroethylamine (0.08 g, 0.82 mmol). The solution stirred for 6 h after which the dichloromethane was removed via rotavap. Sat. NaHCO3 and ethyl acetate were added and the organic layer separated and washed with H2O, dried over MgSO4, filtered and concentrated. The resulting oil was triterated with Et2O and formed a white ppt which was filtered and dried under high vacuum to give the title compound as a white powder (0.109, 55%). 1H NMR (400 MHz, CDCl3) δ7.34-7.25 (m, 3H), 7.12 (t, J=7.5 Hz, 2H), 7.01 (t, J=7.7 Hz, 3H), 6.91 (t, J=8.4 Hz, 3H), 6.54 (d, J=8.4 Hz, 2H), 5.81 (s, 1H), 4.29 (s, 2H), 4.01-3.88 (m, 3H), 2.48-2.43 (m, 1H), 1.62-1.49 (m, 2H), 1.27-1.20 (m, 1H). | O=C(NCC(F)(F)F)[C@@H]1C[C@H]1c1ccc(NCc2cccc(Oc3ccccc3)c2)cc1 | null | 55 | null |
914,097 | ord_dataset-c663259b80f947e2a8923796fb0e9a6b | null | 2009-01-01T00:10:00 | true | [N:1]1([CH:7]2[CH2:12][CH2:11][N:10]([C:13]([C:15]3[CH:16]=[C:17]4[C:21](=[CH:22][CH:23]=3)[NH:20][C:19]([C:24]([N:26]3[CH2:31][CH2:30][C:29]([F:33])([F:32])[CH2:28][CH2:27]3)=[O:25])=[CH:18]4)=[O:14])[CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[F:34][C:35]([F:46])([F:45])[C:36]1[CH:37]=[C:38](B(O)O)[CH:39]=[CH:40][CH:41]=1.N1C=CC=CC=1>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[N:1]1([CH:7]2[CH2:12][CH2:11][N:10]([C:13]([C:15]3[CH:16]=[C:17]4[C:21](=[CH:22][CH:23]=3)[N:20]([C:40]3[CH:39]=[CH:38][CH:37]=[C:36]([C:35]([F:46])([F:45])[F:34])[CH:41]=3)[C:19]([C:24]([N:26]3[CH2:31][CH2:30][C:29]([F:33])([F:32])[CH2:28][CH2:27]3)=[O:25])=[CH:18]4)=[O:14])[CH2:9][CH2:8]2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1 | OB(O)c1cccc(C(F)(F)F)c1 | O=C(c1ccc2[nH]c(C(=O)N3CCC(F)(F)CC3)cc2c1)N1CCC(N2CCCCC2)CC1 | null | [Cu+2] | CC(=O)[O-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | c1ccncc1 | ClCCl | null | null | null | null | null | null | null | null | null | null | null | The title compound was synthesized in analogy to example 66, from [5-([1,4′]bipiperidinyl-1′-carbonyl)-1H-indol-2-yl]-(4,4-difluoro-piperidin-1-yl)-methanone (example 168), 3-(trifluoromethyl)phenylboronic acid, copper(II) acetate and pyridine in dichloromethane, to give the desired product as a brown oil (66%). | O=C(c1ccc2c(c1)cc(C(=O)N1CCC(F)(F)CC1)n2-c1cccc(C(F)(F)F)c1)N1CCC(N2CCCCC2)CC1 | null | 66 | null |
1,197,208 | ord_dataset-4e81c470cc3b429faf5e1caa50f70a98 | null | 2012-01-01T00:08:00 | true | C(O[C:4](=[O:14])[C:5]([C:8]1[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=1)=[CH:6]O)C.[NH:15]([C:17]1[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[CH:19][N:18]=1)[NH2:16]>>[N:10]1[CH:11]=[CH:12][CH:13]=[C:8]([C:5]2[C:4](=[O:14])[N:15]([C:17]3[CH:22]=[C:21]([C:23]([F:26])([F:24])[F:25])[CH:20]=[CH:19][N:18]=3)[NH:16][CH:6]=2)[CH:9]=1 | CCOC(=O)C(=CO)c1cccnc1 | NNc1cc(C(F)(F)F)ccn1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The compound is prepared analogously to Example 2 from 18 mg (0.09 mmol) of the compound from Example 2A and 18 mg (0.10 mmol) 2-hydrazino-4-(trifluoromethyl)pyridine [R. A. Evans, C. Wentrup, J. Chem. Soc. Chem. Commun. 15, 1062-1064 (1992)]. 11.7 mg (41% of th.) of the title compound are obtained as a yellow solid. | O=c1c(-c2cccnc2)c[nH]n1-c1cc(C(F)(F)F)ccn1 | null | null | null |
1,529,412 | ord_dataset-8c74302143c04eb9983e4b3a7ead2d72 | null | 2014-01-01T00:12:00 | true | [C:1]([O:4][CH2:5][C:6]1[C:7]([N:40]2[CH2:51][CH2:50][N:49]3[C:42](=[CH:43][C:44]4[CH2:45][C:46]([CH3:53])([CH3:52])[CH2:47][C:48]=43)[C:41]2=[O:54])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:13]=[C:14]([NH:20][C:21]2[N:26]=[CH:25][C:24]([N:27]3[CH2:32][CH2:31][N:30](C(OC(C)(C)C)=O)[CH2:29][CH2:28]3)=[CH:23][CH:22]=2)[C:15](=[O:19])[N:16]([CH3:18])[CH:17]=1)(=[O:3])[CH3:2].Cl.CO>>[C:1]([O:4][CH2:5][C:6]1[C:7]([N:40]2[CH2:51][CH2:50][N:49]3[C:42](=[CH:43][C:44]4[CH2:45][C:46]([CH3:53])([CH3:52])[CH2:47][C:48]=43)[C:41]2=[O:54])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:13]=[C:14]([NH:20][C:21]2[CH:22]=[CH:23][C:24]([N:27]3[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]3)=[CH:25][N:26]=2)[C:15](=[O:19])[N:16]([CH3:18])[CH:17]=1)(=[O:3])[CH3:2] | CC(=O)OCc1c(-c2cc(Nc3ccc(N4CCN(C(=O)OC(C)(C)C)CC4)cn3)c(=O)n(C)c2)ccnc1N1CCn2c(cc3c2CC(C)(C)C3)C1=O | null | 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 | 4 | A mixture of 339d (130 mg, 0.18 mmol) and HCl/methanol (4.0 mL) was stirred at room temperature for 4 h. It was then concentrated under reduced pressure to afford crude 339e (100 mg, 87%), which was used in the next step without further purification. MS-ESI: [M+H]+ 637.3. | CC(=O)OCc1c(-c2cc(Nc3ccc(N4CCNCC4)cn3)c(=O)n(C)c2)ccnc1N1CCn2c(cc3c2CC(C)(C)C3)C1=O | null | 87.2 | null |
567,400 | ord_dataset-5c8a417a8ba04cf0b7f78b9db9af1d01 | null | 2002-01-01T00:10:00 | true | [O:1]([C:8]1[CH:13]=[CH:12][C:11]([CH:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:20][O:21][C:22]1[C:29]([O:30][CH3:31])=[C:28]([O:32][CH3:33])[CH:27]=[CH:26][C:23]=1[CH:24]=O.C(O)=O.C(=O)([O-])O.[Na+]>C(OCC)(=O)C>[O:1]([C:8]1[CH:13]=[CH:12][C:11]([CH:14]2[CH2:19][CH2:18][N:17]([CH2:24][C:23]3[CH:26]=[CH:27][C:28]([O:32][CH3:33])=[C:29]([O:30][CH3:31])[C:22]=3[O:21][CH3:20])[CH2:16][CH2:15]2)=[CH:10][CH:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1 | COc1ccc(C=O)c(OC)c1OC | c1ccc(Oc2ccc(C3CCNCC3)cc2)cc1 | null | O=C([O-])O | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O=CO | CCOC(C)=O | null | null | null | null | null | null | null | null | null | 120 | null | A mixture of 1.27 g of the compound (9) synthesized in Example 2 and 0.8 g of 2,3,4-trimethoxybenzaldehyde was stirred at 120° C., then, 0.18 ml of formic acid was added dropwise. This was stirred for one hour at the same temperature, then ethyl acetate and a saturated aqueous solution of sodium hydrogencarbonate were added and the results were shaken. The organic layer was dried, filtered, then concentrated under reduced pressure to obtain a residue which was then purified by silica gel column chromatography (hexane:ethyl acetate=3:2) to obtain the above-referenced compound (29) in an amount of 1.46 g (yield 73%). | COc1ccc(CN2CCC(c3ccc(Oc4ccccc4)cc3)CC2)c(OC)c1OC | null | 73 | null |
495,553 | ord_dataset-9df8b3ec9c8742b3802e0efaac6f6ef3 | null | 2001-01-01T00:03:00 | true | [NH2:1][C@@H:2]([C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[C:10]([O:16][CH3:17])[CH:9]=1)[CH2:3][C:4]([O:6][CH3:7])=[O:5].C(=O)([O-])[O-].[Na+].[Na+].C(N1[C:33](=[O:34])[C:32]2=[CH:35][CH:36]=[CH:37][CH:38]=[C:31]2[C:30]1=[O:39])(OCC)=O>>[C:30]1(=[O:39])[N:1]([C@@H:2]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[C:10]([O:16][CH3:17])[CH:9]=2)[CH2:3][C:4]([O:6][CH3:7])=[O:5])[C:33](=[O:34])[C:32]2=[CH:35][CH:36]=[CH:37][CH:38]=[C:31]12 | COC(=O)C[C@@H](N)c1ccc(OC)c(OC)c1 | CCOC(=O)N1C(=O)c2ccccc2C1=O | null | O=C([O-])[O-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Methyl (3R)-3-amino-3-(3,4-dimethoxyphenyl)propionate (0.25 g, 0.91 mmol), sodium carbonate (0.10 g, 0.91 mmol) and N-carboethoxyphthalimide (0.20 g, 0.91 mmol) were allowed to react according to the procedure of Example 85. Methyl (3R)-3-phthalimido-3-(3,4-dimethoxyphenyl)propionate was obtained as a white powder, 0.29 g (88%); 1H NMR (DMSO-d6, 250 MHz) δ7.87 (br s, 4H, Ar), 6.80-7.10 (m, 3H, Ar), 5.64 (dd, 1H, J1=7 Hz, J2=9 Hz), 3.73 (s, 3H, OCH3), 3.72 (s, 3H, OCH3), 355 (s, 3H, OCH3), 3.30-3.67 (m, 2H); 13C NMR (DMSO-d6) δ170.8, 167.6, 148.6, 148.4, 134.7, 131.1, 131.0, 123.2, 119.2, 111.7, 111.0, 55.5, 51.6, 49.9, 35.6. Anal. Calcd for C20H19NO60.80 H2O. Theoretical C, 62.60; H, 4.99; N, 3.69. Found C, 62.60; H, 4.93; N, 3.69. HPLC 99.9%. | COC(=O)C[C@H](c1ccc(OC)c(OC)c1)N1C(=O)c2ccccc2C1=O | null | null | null |
1,152,786 | ord_dataset-b195433d5c354ddfb6cde0d53c41910f | null | 2012-01-01T00:04:00 | true | [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]([NH:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[C:15]3[C:10]([CH:11]=[CH:12][CH:13]=[CH:14]3)=[N:9]2)=[CH:4][CH:3]=1.[CH:24]1([N:30]=[C:31]=[O:32])[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]([N:17]([C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)[C:31]([NH:30][CH:24]3[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]3)=[O:32])=[C:15]3[C:10]([CH:11]=[CH:12][CH:13]=[CH:14]3)=[N:9]2)=[CH:6][CH:7]=1 | O=C=NC1CCCCC1 | Clc1ccc(-n2nc3ccccc3c2Nc2ccccc2)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Cc1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | null | In analogy to the procedure described in example 1.2, [2-(4-chloro-phenyl)-2H-indazol-3-yl]-phenyl-amine was reacted with cyclohexylisocyanate ([3173-53-3]) in toluene for 5 days under reflux conditions to give the title compound as yellow oil. MS: m/e=445.1 [M+H+]. | O=C(NC1CCCCC1)N(c1ccccc1)c1c2ccccc2nn1-c1ccc(Cl)cc1 | null | null | null |
1,492,201 | ord_dataset-366bdd9ee72d474cbe6f3f9e54dd96d2 | null | 2014-01-01T00:10:00 | true | [OH:1][B:2]1[C:6]2[CH:7]=[CH:8][C:9]([CH:11]=[N:12][OH:13])=[CH:10][C:5]=2[C:4]([CH3:15])([CH3:14])[O:3]1.C1C(=O)N([Cl:23])C(=O)C1>CN(C=O)C>[OH:13]/[N:12]=[C:11](\[Cl:23])/[C:9]1[CH:8]=[CH:7][C:6]2[B:2]([OH:1])[O:3][C:4]([CH3:15])([CH3:14])[C:5]=2[CH:10]=1 | O=C1CCC(=O)N1Cl | CC1(C)OB(O)c2ccc(C=NO)cc21 | 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 | 45 | 3 | To a solution of 1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborole-5-carbaldehyde oxime (1.38 g, 6.73 mmol) in DMF (15 mL) at rt was added NCS (1.07 g, 8.03 mmol). The reaction mixture was warmed to 45° C., stirred for 3 h and cooled to rt. The mixture was poured into ice-water (20 mL) and extracted with EA (20 mL×2). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure to give the desired product (1.7 g; 100% yield) as a white solid. | CC1(C)OB(O)c2ccc(/C(Cl)=N/O)cc21 | null | 105.5 | null |
925,254 | ord_dataset-cc0899cd744f4f7f8e7f2463560faad1 | null | 2009-01-01T00:12:00 | true | [CH2:1]([O:3][C:4](=[O:19])[C:5](=O)[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]#[N:14])=[CH:9][C:8]=1[N+:15]([O-])=O)[CH3:2].[H][H]>CCO>[CH2:1]([O:3][C:4]([C:5]1[NH:15][C:8]2[C:7]([CH:6]=1)=[CH:12][CH:11]=[C:10]([C:13]#[N:14])[CH:9]=2)=[O:19])[CH3:2] | [H][H] | CCOC(=O)C(=O)Cc1ccc(C#N)cc1[N+](=O)[O-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | null | null | null | null | null | null | null | null | null | null | null | null | Add to 1.5 g of 3-(4-cyano-2-nitrophenyl)-2-oxopropionic acid ethyl ester, in EtOH (40 mL) 10% Pd/C (0.45 g) and stir under a hydrogen atmosphere until the theoretical amount of hydrogen is absorbed. Filter the mixture and concentrate the filtrate to afford 1.1 g of crude product. Purify by chromatography on SiO2 and elute with CH2Cl2. Concentrate the desired fractions and vacuum dry the residue over night (40° C.) to afford the title compound (0.8 g) as white crystals, mp 176° C. | CCOC(=O)c1cc2ccc(C#N)cc2[nH]1 | null | 65.3 | null |
666,328 | ord_dataset-c5ee194443334d3e92aff17e46e33bd1 | null | 2005-01-01T00:04:00 | true | [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][NH2:10])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:18][CH2:19][CH2:20][N:21]1[C:25](=[O:26])[C:24]2=[CH:27][CH:28]=[CH:29][CH:30]=[C:23]2[C:22]1=[O:31]>CC#N>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][NH:10][CH2:18][CH2:19][CH2:20][N:21]2[C:25](=[O:26])[C:24]3=[CH:27][CH:28]=[CH:29][CH:30]=[C:23]3[C:22]2=[O:31])=[CH:4][CH:3]=1 | NCCc1ccc(Cl)cc1 | O=C1c2ccccc2C(=O)N1CCCBr | 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 | null | 16 | To a mixture of 2-(4-chlorophenyl)ethylamine (1.56 g, 10 mmol) and potassium carbonate (2.8 g, 20 mmol) in CH3CN (50 ml) was added N-(3-bromopropyl)phthalimide (3.0 g, 11 mmol). The mixture was refluxed under stirring for 16 h, and then filtered. The filtrate was concentrated under vacuum to dryness, and the residue was chromatographed on silica gel (eluting with 2.5% methanol/chloroform) to afford N-[3-[2-(4-chlorophenyl)ethylamino]propyl]phthalimide (2.28 g, 67%): MS(FD) m/e 343 [M+H]+; 1H NMR (400 MHz, CDCl3) δ 7.84 (m, 2H), 7.71 (m, 2H), 7.24 (d, J=8.3 Hz, 2H), 7.11 (d, J=8.3 Hz, 2H), 3.74 (d, J=6.8 Hz, 2H), 2.82 (t, J=6.8 Hz, 2H), 2.73 (t, J=6.8 Hz, 2H), 2.66 (t, J=6.8 Hz, 2H), 1.84 (m, 2H). | O=C1c2ccccc2C(=O)N1CCCNCCc1ccc(Cl)cc1 | null | 66.5 | null |
20,296 | ord_dataset-2a1960001e7d4e89987253631df1362a | null | 1977-01-01T00:02:00 | true | C(O[C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7][CH2:6][N:5]=1)C.[NH:14]([C:16]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH2:19][CH2:18][N:17]=1)[NH2:15]>CO>[N:15](=[C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7][CH2:6][NH:5]1)[N:14]=[C:16]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH2:19][CH2:18][NH:17]1 | NNC1=NCCc2ccccc21 | CCOC1=NCCc2ccccc21 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | null | null | A solution of 1-ethoxy-3,4-dihydroisoquinoline (4.25 g.) and 1-hydrazino-3,4-dihydroisoquinoline (3.9 g.) in methanol (40 ml.) was stirred at room temperature overnight and then at reflux for a day. More 1-ethoxy-3,4-dihydroisoquinoline (1 g.) was added during the reflux period. The solution was stripped of methanol and the solid was recrystallized from 2-propanol, affording 1,1'-azinobis(1,2,3,4-tetrahydroisoquinoline) (II: Y=Y' =Z=Z' H) (first crop, 2.6 g., m.p. 178°-179° C.). In this example 1-hydrazino-3,4-dihydroisoquinoline hydrochloride can be used instead of 1-hydrazino-3,4-dihydroisoquinoline. | c1ccc2c(c1)CCNC2=NN=C1NCCc2ccccc21 | null | null | null |
1,257,891 | ord_dataset-266f60b4555945d6afb2d2bdf5fa04e0 | null | 2013-01-01T00:02:00 | true | [NH2:1][C:2]([CH:4]1[CH2:9][O:8][CH2:7][CH2:6][N:5]1C(OC(C)(C)C)=O)=[O:3].O1CCOCC1.[ClH:23]>>[ClH:23].[NH:5]1[CH2:6][CH2:7][O:8][CH2:9][CH:4]1[C:2]([NH2:1])=[O:3] | CC(C)(C)OC(=O)N1CCOCC1C(N)=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 | 25 | null | 1,1-Dimethylethyl 3-(aminocarbonyl)morpholine-4-carboxylate (0.48 g, 2.085 mmol) was taken up in 4 M HCl in dioxane (5 mL, 10.00 mmol) and maintained at room temperature overnight. The solvent was removed in vacuo to afford the title compound as a pale yellow solid. | NC(=O)C1COCCN1 | null | null | null |
127,726 | ord_dataset-e61c1950b2fc468dbf0701c65768f73f | null | 1985-01-01T00:03:00 | true | [CH3:1][N:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.[C:8]12([NH:18][S:19]([C:22]3[CH:33]=[C:26]4[C:27](OC(=O)[NH:31][C:25]4=[CH:24][CH:23]=3)=[O:28])(=[O:21])=[O:20])[CH2:17][CH:12]3[CH2:13][CH:14]([CH2:16][CH:10]([CH2:11]3)[CH2:9]1)[CH2:15]2>C1(C)C=CC=CC=1>[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:27](=[O:28])[C:26]2[C:25](=[CH:24][CH:23]=[C:22]([S:19](=[O:21])(=[O:20])[NH:18][C:8]34[CH2:17][CH:12]5[CH2:13][CH:14]([CH2:16][CH:10]([CH2:11]5)[CH2:9]3)[CH2:15]4)[CH:33]=2)[NH2:31])[CH2:4][CH2:3]1 | O=c1[nH]c2ccc(S(=O)(=O)NC34CC5CC(CC(C5)C3)C4)cc2c(=O)o1 | CN1CCNCC1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Cc1ccccc1 | null | null | null | null | null | null | null | null | null | null | 25 | null | 2.7 g of 1-methylpiperazine are added slowly to a suspension of 10.2 g of 5-[N-(1-adamantyl)-sulfamoyl]-isatoic anhydride in 250 ml of absolute toluene, at 100° with stirring. After the addition is ended, the mixture is stirred for a further 1 hour at 100° and is allowed to cool to room temperature, the precipitate is separated off by decanting and the crude product thus obtained is recrystallised from ethanol. 5-[N-(1-Adamantyl)-sulfamoyl]-anthranilic acid (4-methyl)-piperazide with a melting point of 214°-215° is obtained. (Melting point of the hydrochloride: 298°-300°). | CN1CCN(C(=O)c2cc(S(=O)(=O)NC34CC5CC(CC(C5)C3)C4)ccc2N)CC1 | null | null | null |
372,905 | ord_dataset-ee5599340390470d8e5b5ac1feddf9d6 | null | 1997-01-01T00:08:00 | true | C[O-].[Na+].I.[CH2:5]([S:7][C:8](=[NH:10])[NH2:9])[CH3:6].C(O[CH:14]=[C:15]([C:18]#[N:19])[C:16]#[N:17])C>CCO>[NH2:19][C:18]1[C:15]([C:16]#[N:17])=[CH:14][N:9]=[C:8]([S:7][CH2:5][CH3:6])[N:10]=1 | CCOC=C(C#N)C#N | CCSC(=N)N | null | C[O-] | I | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | null | null | null | null | null | null | null | null | null | null | 25 | null | A suspension of NaOMe (2.7 g, 50 mmol) in EtOH (200 mL) is added to a mixture of S-ethylisothiourea hydroiodide (11.58 g, 50 mmol), ethoxymethylidenemalononitrile (6.1 g, 50 mmol) and ethanol (250 mL) at 25° C. The reaction mixture is refluxed under N2 for 2 h, and then the solution is concentrated on a hot plate until precipitation is observed. After cooling, the solid is collected by suction filtration and is stirred in water at 25° C. Filtration and vacuum oven drying affords 4-amino-5-cyano-2-ethylthiopyrimidine (4.02 g, 45%) as a brown solid. 1H NMR δ (DMSO) 8.45 (1H, s), 7.90 (2H, brs), 3.00 (2H, q, J=7.3 Hz), 1.27 (3H, t, J=7.3 Hz). | CCSc1ncc(C#N)c(N)n1 | null | 44.6 | null |
1,666,389 | ord_dataset-9cc455db05a444779921f786a45b21a6 | null | 2015-01-01T00:12:00 | true | [NH2:1][CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.[Cl:11][C:12]1[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:13]=1[C:19]1[CH:20]=[C:21]([C:24](Cl)=[O:25])[NH:22][N:23]=1>N1C=CC=CC=1>[OH:10][C:7]1[CH:8]=[CH:9][C:4]([CH2:3][CH2:2][NH:1][C:24]([C:21]2[NH:22][N:23]=[C:19]([C:13]3[CH:14]=[CH:15][C:16]([Cl:18])=[CH:17][C:12]=3[Cl:11])[CH:20]=2)=[O:25])=[CH:5][CH:6]=1 | O=C(Cl)c1cc(-c2ccc(Cl)cc2Cl)n[nH]1 | NCCc1ccc(O)cc1 | 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 | null | null | In pyridine (6 ml), 4-(2-amino-ethyl)-phenol (72 mg) was dissolved, and 5-(2,4-dichlorophenyl)-2H-pyrazole-3-carboxylic acid chloride (137 mg) was added thereto under an ice cooling while stirring. Thereafter, the mixture was stirred at a room temperature for 17 hours and then concentrated under a reduced pressure, and the concentrate was purified by silica gel column chromatography (5% methanol-chloroform) to give the title compound (132 mg, 70%). | O=C(NCCc1ccc(O)cc1)c1cc(-c2ccc(Cl)cc2Cl)n[nH]1 | null | 70.6 | null |
809,008 | ord_dataset-da49b0378abf41bf92ab8ecdd3feb28b | null | 2008-01-01T00:02:00 | true | [Cl:1][C:2]1[CH:7]=[C:6]([C:8]#[C:9][C:10]2[N:11]=[C:12]([CH3:15])[NH:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1.[F:16][C:17]1[CH:18]=[C:19](B(O)O)[CH:20]=[CH:21][C:22]=1[F:23]>>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]#[C:9][C:10]2[N:11]=[C:12]([CH3:15])[N:13]([C:20]3[CH:19]=[CH:18][C:17]([F:16])=[C:22]([F:23])[CH:21]=3)[CH:14]=2)[CH:5]=[CH:4][N:3]=1 | OB(O)c1ccc(F)c(F)c1 | Cc1nc(C#Cc2ccnc(Cl)c2)c[nH]1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The title compound, MS: m/e=330.4 (M+H+), was prepared in accordance with the general method of example 7 from 2-chloro-4-(2-methyl-1 H-imidazol-4-ylethynyl)-pyridine and 3,4-difluorobenzene boronic acid. | Cc1nc(C#Cc2ccnc(Cl)c2)cn1-c1ccc(F)c(F)c1 | null | null | null |
429,888 | ord_dataset-8cce6f317d644b348a7978a2dce3ea01 | null | 1999-01-01T00:03:00 | true | [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:11][CH2:10][C:9]3=[N:12][CH:13]=[CH:14][N:8]3[CH2:7][C:6]=2[CH:15]=1.[CH3:16][C:17]1[CH:34]=[CH:33][CH:32]=[CH:31][C:18]=1[C:19]([NH:21][C:22]1[CH:30]=[CH:29][C:25]([C:26](Cl)=[O:27])=[CH:24][CH:23]=1)=[O:20].C(N(CC)CC)C>ClCCl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([C:26]([C:25]3[CH:24]=[CH:23][C:22]([NH:21][C:19](=[O:20])[C:18]4[CH:31]=[CH:32][CH:33]=[CH:34][C:17]=4[CH3:16])=[CH:30][CH:29]=3)=[O:27])[CH2:10][C:9]3=[N:12][CH:13]=[CH:14][N:8]3[CH2:7][C:6]=2[CH:15]=1 | Clc1ccc2c(c1)Cn1ccnc1CN2 | Cc1ccccc1C(=O)Nc1ccc(C(=O)Cl)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(CC)CC | ClCCl | null | null | null | null | null | null | null | null | null | 25 | 3 | As described for Example 125 a mixture of 1 mmol of 7-chloro-10,11-dihydro-5H-imidazo[2,1-c][1,4]benzodiazepine, 1.1 mmol of 4-[(2-methylbenzoyl)amino]benzoyl chloride and 1.5 mmol of triethylamine in 10 ml of dichloromethane is stirred at room temperature for 3 hours and worked up to give the desired product as a solid. | Cc1ccccc1C(=O)Nc1ccc(C(=O)N2Cc3nccn3Cc3cc(Cl)ccc32)cc1 | null | null | null |
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