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 ⌀ |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
37,306 | ord_dataset-3e699bae9dce4a0f996c34a7c5a4b79a | null | 1978-01-01T00:02:00 | true | Cl.[CH2:2]1[CH:11]2[N:6]([CH2:7][CH2:8][C:9]3[CH:15]=[CH:14][CH:13]=[CH:12][C:10]=32)[CH2:5][CH2:4][CH:3]1[NH:16][C:17]([NH:19]C(=O)C1C=CC=CC=1)=[O:18]>[OH-].[Na+]>[CH2:2]1[CH:11]2[N:6]([CH2:7][CH2:8][C:9]3[CH:15]=[CH:14][CH:13]=[CH:12][C:10]=32)[CH2:5][CH2:4][CH:3]1[NH:16][C:17]([NH2:19])=[O:18] | O=C(NC(=O)c1ccccc1)NC1CCN2CCc3ccccc3C2C1 | null | null | Cl | [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 | null | 1-(1,3,4,6,7,11b-Hexahydro-2H-benzo[a]quinolizin-2-yl)-3-benzoylurea hydrochloride (0.98 g) was refluxed in 2N sodium hydroxide solution (50 ml) for 4 hours. The solution was filtered and the residue washed with water, then ethanol, and finally ether before drying to give the title compound (0.46 g) melting point 235° C. C14H19N3O requires: C, 68.54%; H, 7.81%; N, 17.13%. Found: C, 68.53%; H, 7.79%; N, 17.33%. | NC(=O)NC1CCN2CCc3ccccc3C2C1 | null | 73.8 | null |
1,770,938 | ord_dataset-0b32b90cc77b4a3db47ad263e0bbc1a8 | null | 2016-01-01T00:09:00 | true | [CH:1]1([CH2:7][O:8][C:9]2[C:10]3[N:11]([C:15]([C:19]([NH:21][CH:22]4[CH2:27][CH2:26][N:25](C(OC(C)(C)C)=O)[CH2:24][CH2:23]4)=[O:20])=[C:16]([CH3:18])[N:17]=3)[CH:12]=[CH:13][CH:14]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[ClH:35].C(OCC)(=O)C>C(OCC)(=O)C>[ClH:35].[ClH:35].[CH:1]1([CH2:7][O:8][C:9]2[C:10]3[N:11]([C:15]([C:19]([NH:21][CH:22]4[CH2:23][CH2:24][NH:25][CH2:26][CH2:27]4)=[O:20])=[C:16]([CH3:18])[N:17]=3)[CH:12]=[CH:13][CH:14]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1 | Cc1nc2c(OCC3CCCCC3)cccn2c1C(=O)NC1CCN(C(=O)OC(C)(C)C)CC1 | null | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOC(C)=O | null | null | null | null | null | null | null | null | null | null | null | 24 | To a solution of 1.44 g of tert-butyl 4-({[8-(cyclohexylmethoxy)-2-methylimidazo[1,2-a]pyridin-3-yl]carbonyl}amino)piperidine-1-carboxylate in 15 ml of ethyl acetate was added 3.8 ml of a 4 M hydrogen chloride/ethyl acetate solution, followed by stirring for 1 day. The reaction mixture was concentrated under reduced pressure, and to the obtained residue were added ethyl acetate and ethanol. The resulting solid was collected by filtration and dried to obtain 1.29 g of 8-(cyclohexylmethoxy)-2-methyl-N-(piperidin-4-yl)imidazo[1,2-a]pyridine-3-carboxamide dihydrochloride. | Cc1nc2c(OCC3CCCCC3)cccn2c1C(=O)NC1CCNCC1 | null | null | null |
1,694,634 | ord_dataset-c1e70ad912eb438f8d34b1dc681f809a | null | 2016-01-01T00:02:00 | true | [Br:1][C:2]1[C:11]([F:12])=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([CH3:13])[CH:3]=1.[Br:14]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl.C(Cl)Cl.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>[Br:1][C:2]1[C:11]([F:12])=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([CH2:13][Br:14])[CH:3]=1 | O=C1CCC(=O)N1Br | COC(=O)c1cc(F)c(Br)cc1C | null | O=C(OOC(=O)c1ccccc1)c1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClC(Cl)(Cl)Cl | ClCCl | null | null | null | null | null | null | null | null | null | null | null | A mixture of methyl 4-bromo-5-fluoro-2-methylbenzoate (1.0 g, 4.0 mmol) (Ellanoval Laboratories Cat. No. 38-0304), N-bromosuccinimide (900. mg, 5.06 mmol) and benzoyl peroxide (50 mg, 0.2 mmol) in carbon tetrachloride (50 mL) was refluxed under a nitrogen atmosphere for 4 h. After cooling the mixture was diluted with methylene chloride. The organic solution was washed with brine, then dried over Na2SO4. After filtration the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexanes (0-50%) to afford the desired product (1.2 g). | COC(=O)c1cc(F)c(Br)cc1CBr | null | 92 | null |
180,600 | ord_dataset-ed5a3d1f8dc744759e7fa1c320a44e59 | null | 1988-01-01T00:11:00 | true | [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]3=[N:19][N:20]=[C:21](S(C)=O)[N:11]3[N:10]=2)=[CH:5][CH:4]=1.[NH:25]1[CH2:29][CH2:28][CH2:27][CH2:26]1>>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]3=[N:19][N:20]=[C:21]([N:25]4[CH2:29][CH2:28][CH2:27][CH2:26]4)[N:11]3[N:10]=2)=[CH:5][CH:4]=1 | COc1ccc(-c2nn3c(S(C)=O)nnc3c3ccccc23)cc1 | C1CCNC1 | null | null | null | null | null | null | null | 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 6-(4-methoxyphenyl)-3-(methylsulfinyl)-1,2,4-triazolo[3,4-a]phthalazine (3.5 g) and pyrrolidine (30 ml) is heated to 120°/140° C. in a steel bomb for 16 hours. The mixture is then cooled, and the excess of the amine is evaporated off yielding a residue which is washed carefully with a small amount of water and crystallized from 70% ethanol. Yield: 45%. M.p. 196°-98° C. | COc1ccc(-c2nn3c(N4CCCC4)nnc3c3ccccc23)cc1 | null | 45 | null |
1,042,806 | ord_dataset-3af92aec23dc4810b92eb0d8c60023ee | null | 2011-01-01T00:03:00 | true | C([Li])CCC.CC1(C)CCCC(C)(C)N1.[C:16]([O:20][C:21]([NH:23][C:24]1[CH:29]=[N:28][CH:27]=[CH:26][N:25]=1)=[O:22])([CH3:19])([CH3:18])[CH3:17].CN([CH:33]=[O:34])C>O1CCCC1>[C:16]([O:20][C:21]([NH:23][C:24]1[C:29]([CH:33]=[O:34])=[N:28][CH:27]=[CH:26][N:25]=1)=[O:22])([CH3:19])([CH3:17])[CH3:18] | CC(C)(C)OC(=O)Nc1cnccn1 | CN(C)C=O | null | CC1(C)CCCC(C)(C)N1 | [Li]CCCC | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | -70 | 0.5 | After adding 4 ml of n-butyllithium (2.46 M, n-hexane solution) to a solution of 1.384 g of 2,2,6,6-tetramethylpiperidine in tetrahydrofuran (15 ml) at −20° C. under a nitrogen atmosphere, the mixture was stirred for 30 minutes while cooling on ice. The reaction mixture was cooled to −70° C., and then a solution of 800 mg of 2-(tert-butoxycarbonylamino)pyrazine in tetrahydrofuran (3 ml) was added dropwise, the mixture was stirred for 1 hour, 3 ml of N,N-dimethylformaldehyde was added, and stirring was continued for 30 minutes. After removing the cooling bath and stirring for 30 minutes, water was added and extraction was performed with ethyl acetate. The extract was dried and concentrated and then purified by silica gel column chromatography (solvent: ethyl acetate/n-hexane) to obtain 72 mg of crude 2-(tert-butoxycarbonylamino)pyrazine-3-carboxaldehyde. | CC(C)(C)OC(=O)Nc1nccnc1C=O | null | null | null |
693,729 | ord_dataset-35824232b132464aa99e71aba765981d | null | 2005-01-01T00:12:00 | true | [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@@H:9]([NH:29][C:30]([C@@H:32]2[CH2:41][C:40]3[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=3)[CH2:34][N:33]2C(OC(C)(C)C)=O)=[O:31])[C:10]([N:12]2[CH2:17][CH2:16][CH:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[NH:24][CH2:25][CH:26]3[CH2:28][CH2:27]3)[CH2:14][CH2:13]2)=[O:11])=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@@H:9]([NH:29][C:30]([C@@H:32]2[CH2:41][C:40]3[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=3)[CH2:34][NH:33]2)=[O:31])[C:10]([N:12]2[CH2:17][CH2:16][CH:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[NH:24][CH2:25][CH:26]3[CH2:28][CH2:27]3)[CH2:14][CH2:13]2)=[O:11])=[CH:4][CH:3]=1 | CC(C)(C)OC(=O)N1Cc2ccccc2C[C@H]1C(=O)N[C@H](Cc1ccc(Cl)cc1)C(=O)N1CCC(c2ccccc2NCC2CC2)CC1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O=C(O)C(F)(F)F | ClCCl | null | null | null | null | null | null | null | null | null | null | 0.5 | The title compound was prepared according to the procedure described in Example 3 (Step b) using tert-butyl 3-{N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-(2-[(cyclopropylmethyl)-amino]phenyl}piperidyl)-2-oxoethyl]carbamoyl}(3S)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate (Step a) (431 mg, 0.64 mmol) and 50% TFA in CH2Cl2 (20 mL). Purification by reverse phase preparative HPLC [Phenomenex; 5 μm 250×21.2 mm, 5% to 95% CH3CN (0.1% TFA) in H2O (0.1% TFA) over 30 min, then 100% CH3CN (0.1% TFA) for 2 min] provided the title compound (TFA salt) as a white foam (207 mg). MS (ESI, pos. ion) m/z: 571 (M+1); (ESI, neg. ion) m/z: 569 (M−1). Calc'd for C34H39ClN4O2: 570.28. Anal. Calcd for C34H39ClN4O2-2.4C2HF3O2: C, 55.16; H, 4.94; N, 6.63. Found: C, 55.18; H, 5.13; N, 6.61. | O=C(N[C@H](Cc1ccc(Cl)cc1)C(=O)N1CCC(c2ccccc2NCC2CC2)CC1)[C@@H]1Cc2ccccc2CN1 | null | null | null |
229,086 | ord_dataset-9adbd9cd2fd941f7af27fb31c9bf3bac | null | 1991-01-01T00:06:00 | true | [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][N:12]([C:15]3[CH:16]=[CH:17][C:18]([N+:21]([O-])=O)=[N:19][CH:20]=3)[CH2:11][CH2:10]2)=[CH:5][CH:4]=1>C(OCC)(=O)C.[Pt]>[NH2:21][C:18]1[CH:17]=[CH:16][C:15]([N:12]2[CH2:13][CH2:14][N:9]([C:6]3[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)[CH2:10][CH2:11]2)=[CH:20][N:19]=1 | COc1ccc(N2CCN(c3ccc([N+](=O)[O-])nc3)CC2)cc1 | null | null | [Pt] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOC(C)=O | null | null | null | null | null | null | null | null | null | null | null | 12 | A suspension of the product of part (i) (0.65 g, 2.0 mmole) in ethyl acetate (30 ml) was hydrogenated over 5% platinum on carbon (25 mg) at 45 p.s.i. (310 kPa) and at 50° for 12 hours, followed by 45 hours at room temperature. The resulting mixture was filtered to remove the catalyst, concentrated under reduced pressure and the residue triturated with ether to yield the desired product, m.p. 182°-188° (0.28 g, 50%), which was used without further purification. | COc1ccc(N2CCN(c3ccc(N)nc3)CC2)cc1 | null | null | null |
1,599,000 | ord_dataset-e8c6a25568b64529b960953990e6921f | null | 2015-01-01T00:06:00 | true | [N:1]1[CH:6]=[CH:5][C:4]([CH2:7][CH:8](C(C(OCC)=O)C(OCC)=O)[CH3:9])=[CH:3][CH:2]=1.[C:21](=[O:24])(O)[O-:22].[Na+]>Cl>[N:1]1[CH:6]=[CH:5][C:4]([CH2:7][CH:8]([CH3:9])[C:21]([OH:22])=[O:24])=[CH:3][CH:2]=1 | O=C([O-])O | CCOC(=O)C(C(=O)OCC)C(C)Cc1ccncc1 | 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 | Compound diethyl 2-(1-(pyridin-4-yl)propan-2-yl)malonate (2.50 g, 9.43 mmol) was refluxed in cone. HCl (30 ml) for 16 h. The pH of the reaction mixture was adjusted to 6 by adding solid sodium bicarbonate and extracted with ethyl acetate. The combined ethyl acetate layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuum to afford 1.20 g (76.9%) of 2-((pyridin-4-yl)methyl)propanoic acid as an off-white solid. | CC(Cc1ccncc1)C(=O)O | null | 76.9 | null |
919,205 | ord_dataset-8e59bd24817446f7b1c68e805b8e5f1d | null | 2009-01-01T00:11:00 | true | Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][CH:9]2[CH2:14][C:13]([CH3:16])([CH3:15])[NH:12][C:11]([CH3:18])([CH3:17])[CH2:10]2)[N:3]=1.CC1(C)C(C)(C)OB([C:27]2[CH:32]=[CH:31][C:30]([CH2:33][C:34](=[O:36])[CH3:35])=[CH:29][CH:28]=2)O1>>[CH3:15][C:13]1([CH3:16])[CH2:14][CH:9]([NH:8][C:4]2[N:3]=[C:2]([C:27]3[CH:32]=[CH:31][C:30]([CH2:33][C:34](=[O:36])[CH3:35])=[CH:29][CH:28]=3)[CH:7]=[CH:6][N:5]=2)[CH2:10][C:11]([CH3:18])([CH3:17])[NH:12]1 | CC(=O)Cc1ccc(B2OC(C)(C)C(C)(C)O2)cc1 | CC1(C)CC(Nc2nccc(Cl)n2)CC(C)(C)N1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The title compound was prepared from (4-chloro-pyrimidin-2-yl)(2,2,6,6-tetramethyl-piperidin-4-yl)-amine and 1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propan-2-one according to Method C (Example 178). Yield: 160 mg (78%). | CC(=O)Cc1ccc(-c2ccnc(NC3CC(C)(C)NC(C)(C)C3)n2)cc1 | null | null | null |
293,842 | ord_dataset-b90b48a6c23149a1aa2d91b92b1a31e4 | null | 1994-01-01T00:07:00 | true | [O:1]=[C:2]([N:5]1[C@H:9]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:8][O:7][C:6]1=[O:17])[CH2:3][CH3:4].[CH3:18][C@@H:19]([CH2:22][O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[CH:20]=[O:21]>>[O:1]=[C:2]([N:5]1[C@H:9]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:8][O:7][C:6]1=[O:17])[C@H:3]([CH3:4])[C@H:20]([OH:21])[C@@H:19]([CH3:18])[CH2:22][O:23][Si:24]([C:27]([CH3:29])([CH3:28])[CH3:30])([CH3:25])[CH3:26] | CCC(=O)N1C(=O)OC[C@H]1Cc1ccccc1 | C[C@H](C=O)CO[Si](C)(C)C(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 | null | This material is prepared from (R)-3-(1-oxopropyl)-4-(phenylmethyl)-2-oxazolidinone and 2-(S)-methyl-3-t-butyldimethylsiloxypropanal following the method of Evans and Gage, as described in Org. Syn., Vol. 68, 19xx, p. 83. | C[C@@H](CO[Si](C)(C)C(C)(C)C)[C@@H](O)[C@@H](C)C(=O)N1C(=O)OC[C@H]1Cc1ccccc1 | null | null | null |
863,412 | ord_dataset-b8b98725045d45bdbd73512048f4b47e | null | 2009-01-01T00:02:00 | true | [CH3:1][O:2][C:3]1[C:17]([O:18][CH3:19])=[CH:16][CH:15]=[CH:14][C:4]=1[CH2:5][NH:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13].[CH2:20]([O:22][C@H:23]([C:36]([O:38][CH2:39][CH3:40])=[O:37])[CH2:24][C:25]1[CH:35]=[CH:34][C:28]([O:29][CH2:30][C:31](O)=[O:32])=[CH:27][CH:26]=1)[CH3:21].C(N(CC)C(C)C)(C)C.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>C(Cl)Cl>[CH3:1][O:2][C:3]1[C:17]([O:18][CH3:19])=[CH:16][CH:15]=[CH:14][C:4]=1[CH2:5][N:6]([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])[C:31](=[O:32])[CH2:30][O:29][C:28]1[CH:27]=[CH:26][C:25]([CH2:24][C@H:23]([O:22][CH2:20][CH3:21])[C:36]([O:38][CH2:39][CH3:40])=[O:37])=[CH:35][CH:34]=1 | CCOC(=O)[C@H](Cc1ccc(OCC(=O)O)cc1)OCC | CCCCCCCNCc1cccc(OC)c1OC | null | CN(C)C(On1nnc2ccccc21)=[N+](C)C | F[B-](F)(F)F | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(C(C)C)C(C)C | ClCCl | null | null | null | null | null | null | null | null | null | 25 | 8 | To a solution of N-(2,3-dimethoxybenzyl)-N-heptylamine (1.46 g, 5.5 mmol) and {4-[(2S)-2,3-diethoxy-3-oxopropyl]phenoxy}acetic acid (1.48 g, 5.0 mmol) in methylene chloride (50 mL) at 0° C. were added N,N-diisopropylethylamine (2.0 mL, 11.5 mmol) and O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (1.93 g, 6.0 mmol) and the reaction mixture was stirred at room temperature overnight and then concentrated in vacuo. The residue was taken up in ethyl acetate (200 mL) and the organic phase was washed with saturated aqueous NaHCO3 (3×100 mL), 5% HCl (3×100 mL), and brine (100 mL), dried over Na2SO4, and concentrated in vacuo. Purification on silica gel (100 g) with methanol (0-2% gradient) in methylene chloride as the eluent and collection of pure fractions yielded 1.57 g (58%) of a pale yellow oil. | CCCCCCCN(Cc1cccc(OC)c1OC)C(=O)COc1ccc(C[C@H](OCC)C(=O)OCC)cc1 | null | 57.8 | null |
893,221 | ord_dataset-11068b1e475b4c5b82e56726ab0dddb7 | null | 2009-01-01T00:07:00 | true | [NH:1]1[CH2:5][CH2:4][N:3]=[C:2]1[C:6]([NH2:26])([C:17]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[C:19]([CH3:25])[CH:18]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([O:13][CH2:14][CH2:15][CH3:16])[CH:8]=1.[N:27]#[C:28]Br>C(Cl)(Cl)Cl>[CH3:24][O:23][C:20]1[CH:21]=[CH:22][C:17]([C:6]2([C:7]3[CH:12]=[CH:11][CH:10]=[C:9]([O:13][CH2:14][CH2:15][CH3:16])[CH:8]=3)[C:2]3=[N:1][CH2:5][CH2:4][N:3]3[C:28]([NH2:27])=[N:26]2)=[CH:18][C:19]=1[CH3:25] | N#CBr | CCCOc1cccc(C(N)(C2=NCCN2)c2ccc(OC)c(C)c2)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClC(Cl)Cl | null | null | null | null | null | null | null | null | null | null | 60 | null | A solution of [4,5-dihydro-1H-imidazol-2-yl(4-methoxy-3-methylphenyl)(3-propoxyphenyl)methyl]amine (0.6 g) in chloroform is treated with cyanogen bromide (0.581 g), heated at 60° C. for 5 days and filtered through a pad of silica. The silica pad was eluted with ethyl acetate, followed by elution with (40:5:5) ethyl acetate: methanol: ammonium hydroxide. The eluents were combined and concentrated in vacuo to give a thick yellow oil, which was purified by Gilson preparative reverse phase HPLC system YMC Pro C18, 20 mm×50 mm ID, 5 uM column; 2 mL injection; Solvent A: 0.02% NH4OH/water; Solvent B:0.02% NH4OH/acetonitrile; Gradient: Time O: 95% A; 2 min: 95% A; 14 min: 10% A, 15 min: 10% A, 16 min: 95% A; Flow rate 22.5 mL/min; Detection: 254 nm DAD to afford the title compound was as an off-white, amphorous solid (0.131 g), characterized by LCMS analysis. LCMS Conditions: HP 1100 HPLC system; Waters Xterra MS C18, 2 mm (i.d.)×50 mm (length), 3.5 um column, set at 50° C.; Flow rate 1.0 mL/min; Solvent A: 0.02% NH4OH in water; Solvent B 0.02% NH4OH in ACN; Gradient: Time O: 10% B; 2.5 min 90% B; 3 min 90% B; Sample concentration: ˜2.0 mM; Injection volume: 5 uL; Detection: 220 nm, 254 nm DAD; retention time: 2.34 min, [M−H] 377, [M+H] 379. | CCCOc1cccc(C2(c3ccc(OC)c(C)c3)N=C(N)N3CCN=C32)c1 | null | null | null |
1,290,896 | ord_dataset-de51ecc8d4434bacaa8bc32d7d73484c | null | 2013-01-01T00:05:00 | true | [Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][C:10]([CH3:14])([CH3:13])[CH2:11][NH2:12])[CH:5]=[C:4]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[CH:21][CH:22]=3)[NH:17][CH:16]=2)[CH:3]=1.C(N(CC)CC)C.[N:31]1[CH:36]=[CH:35][CH:34]=[C:33]([S:37](Cl)(=[O:39])=[O:38])[CH:32]=1>CN(C=O)C>[Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][C:10]([CH3:14])([CH3:13])[CH2:11][NH:12][S:37]([C:33]2[CH:32]=[N:31][CH:36]=[CH:35][CH:34]=2)(=[O:39])=[O:38])[CH:5]=[C:4]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[CH:21][CH:22]=3)[NH:17][CH:16]=2)[CH:3]=1 | O=S(=O)(Cl)c1cccnc1 | CC(C)(CN)CNc1cc(-c2c[nH]c3ncccc23)cc(Cl)n1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(CC)CC | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | 4 | To a solution of Example 74 (55.0 mg, 0.167 mmol) in DMF (1 mL) was added triethylamine (0.070 mL, 0.50 mmol) and pyridine-3-sulfonyl chloride (35.5 mg, 0.200 mmol). After 4 hours, the reaction was quenched with 20% brine and extracted with EtOAc (2×). The organic layers were combined, concentrated, and purified by reverse-phase HPLC as described in Example 56 to give the title compound (28.5 mg) as trifluoroacetic acid salts. 1H NMR (500 MHz, DMSO-d6) ppm 0.89 (s, 6H), 2.68 (d, J=7.02 Hz, 2H), 3.13 (s, 2H), 6.80 (s, brd, 1H), 6.89 (d, J=1.22 Hz, 1H), 6.94 (s, 1H), 7.22 (dd, J=8.09, 4.73 Hz, 1H), 7.60 (dd, J=7.63, 4.58 Hz, 1H), 7.77 (t, J=6.87 Hz, 1H), 8.12-8.18 (m, 2H), 8.28-8.35 (m, 2H), 8.77 (d, J=6.41 Hz, 1H), 8.94 (d, J=2.14 Hz, 1H), 12.19 (s, 1H). MS (APCI+) m/z 471.2 (M+H)+. | CC(C)(CNc1cc(-c2c[nH]c3ncccc23)cc(Cl)n1)CNS(=O)(=O)c1cccnc1 | null | 36.2 | null |
693,742 | ord_dataset-35824232b132464aa99e71aba765981d | null | 2005-01-01T00:12:00 | true | Cl.[Br:2][C:3]1[CH:11]=[C:10]2[C:6]([C:7]([CH2:16][C:17]#[N:18])=[CH:8][N:9]2[S:12]([CH3:15])(=[O:14])=[O:13])=[CH:5][C:4]=1[F:19].[CH2:20](N)[CH2:21][NH2:22]>C(O)C>[Br:2][C:3]1[CH:11]=[C:10]2[C:6]([C:7]([CH2:16][C:17]3[NH:22][CH2:21][CH2:20][N:18]=3)=[CH:8][N:9]2[S:12]([CH3:15])(=[O:14])=[O:13])=[CH:5][C:4]=1[F:19] | NCCN | CS(=O)(=O)n1cc(CC#N)c2cc(F)c(Br)cc21 | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | null | null | null | null | null | null | null | null | null | null | null | 72 | Hydrogen chloride gas was bubbled through a cold (0° C.) suspension of (6-Bromo-5-fluoro-1-methanesulfonyl-1H-indol-3-yl)-acetonitrile (0.215 g, 0.65 mmol) in anhydrous ethanol (20 ml) for 15 minutes. The reaction mixture was refrigerated for 72 hours and the solvent was removed under reduced pressure. The solid residue was re-dissolved in anhydrous methanol (10 ml), and ethylene diamine (0.05 ml, 0.77 mmol) was added. The reaction mixture was heated to reflux for 24 hours and the solvent was removed under reduced pressure. The resulting residue was purified by flash column chromatography over silica gel eluting with 7% methanol in dichloromethane with 0.1% concentrated ammonium hydroxide to give 6-Bromo-3-(4,5-dihydro-1H-imidazol-2-ylmethyl)-5-fluoro-1-methanesulfonyl-1H-indole, which was recrystallized from methanol and ether (0.133 g, 55%). 1H NMR (DMSO) d: 3.56 (s, 3H), 3.82(s, 4H), 4.07 (s, 2H), 7.84 (s, 1H), 7.90 (d, 1H, J=9.1 Hz), 8.10 (d, 1H, J=5.8 Hz), 10.23 (bs, 1H). M+H: 374. | CS(=O)(=O)n1cc(CC2=NCCN2)c2cc(F)c(Br)cc21 | null | null | null |
1,049,369 | ord_dataset-dd320ded4b3f4764af39de99491533f7 | null | 2011-01-01T00:04:00 | true | [C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH3:9])=[CH:5][C:4]=1[NH:10][C:11](=O)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[O:18][CH3:19])#[N:2].[OH-:21].[Na+].OO>C(O)C>[CH3:19][O:18][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[C:11]1[NH:2][C:1](=[O:21])[C:3]2[C:4](=[CH:5][C:6]([CH3:9])=[CH:7][CH:8]=2)[N:10]=1 | [OH-] | COc1ccccc1C(=O)Nc1cc(C)ccc1C#N | null | OO | [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 | 80 | null | To a mechanically stirred suspension of N-(2-cyano-5-methylphenyl)-2-methoxybenzamide (180 g, 0.67 mol) in 1.8 L ethanol under an N2 atmosphere was added 6 N sodium hydroxide solution (310 g in 1.25 L water). To the above mixture, 30% hydrogen peroxide (350 mL, 3.64 mol) was slowly added. The solution was then slowly heated to 80° C. and maintained at this temperature for 4 h. The reaction mixture was concentrated under reduced pressure to remove ethanol, giving a suspension, which was quenched with ice-cold water (1.8 L) and acidified with acetic acid to pH 5-6 to give a solid residue. The solid was filtered and washed with water, then dissolved in 5.5 L CH2Cl2 and washed with water (2×18 L). The organic layer was dried over sodium sulfate, and the solvent was removed under reduced pressure to give a light yellow solid (100 g, 54%). mp 165-170° C. | COc1ccccc1-c1nc2cc(C)ccc2c(=O)[nH]1 | null | 56 | null |
171,005 | ord_dataset-41558b7e18dd41999311b1762e0e13a3 | null | 1988-01-01T00:04:00 | true | [S:1]1[CH2:6][CH2:5][N:4]([CH2:7][N:8]2[C:13](=[O:14])[CH2:12][N:11]([CH2:15][CH:16]([N:18]3[CH2:23][C:22](=[O:24])[N:21](CN4CCSCC4)[C:20](=[O:32])[CH2:19]3)[CH3:17])[CH2:10][C:9]2=[O:33])[CH2:3][CH2:2]1>O>[S:1]1[CH2:6][CH2:5][N:4]([CH2:7][N:8]2[C:13](=[O:14])[CH2:12][N:11]([CH2:15][CH:16]([N:18]3[CH2:19][C:20](=[O:32])[NH:21][C:22](=[O:24])[CH2:23]3)[CH3:17])[CH2:10][C:9]2=[O:33])[CH2:3][CH2:2]1 | CC(CN1CC(=O)N(CN2CCSCC2)C(=O)C1)N1CC(=O)N(CN2CCSCC2)C(=O)C1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | null | null | null | null | null | null | null | null | null | null | 25 | 5 | Water (30 ml) was added to dl-1,2-bis(4-thiomorpholinomethyl-3,5-dioxopiperazin-1-yl)-propane (0.6 g) and the suspension thus obtained was stirred at room temperature for 5 hours. Then, the precipitates thus obtained were collected and were dried under a reduced pressure. Chloroform (10 ml) was added to the dried precipitates and the whole was stirred at room temperature for 20 minutes, then was filtered. The filtration residue was dried under a reduced pressure to give the titled compound (0.2 g; yield 43%). | CC(CN1CC(=O)N(CN2CCSCC2)C(=O)C1)N1CC(=O)NC(=O)C1 | null | 43.3 | null |
181,197 | ord_dataset-ed5a3d1f8dc744759e7fa1c320a44e59 | null | 1988-01-01T00:11:00 | true | C[O:2][C:3](=[O:21])/[CH:4]=[CH:5]/[CH:6]=[C:7](/[C:13]1[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=1)\[CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[OH-].[Na+]>CO>[CH3:20][O:19][C:16]1[CH:15]=[CH:14][C:13](/[C:7](/[CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])=[CH:6]/[CH:5]=[CH:4]/[C:3]([OH:21])=[O:2])=[CH:18][CH:17]=1 | CCCCC/C(=C\C=C\C(=O)OC)c1ccc(OC)cc1 | null | null | [Na+] | [OH-] | 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 | 0.75 | As described in Example 99, (E,E)-5-(4-methoxyphenyl)-2,4-decadienoic acid methyl ester 6.1 g) was saponified in a refluxing mixture of methanol (25 mL) and 2N NaOH (25 mL). After 45 minutes the reaction was worked up in the usual way and the crude acid crystallized from 2-propanol to give 4.7 g of (E,E)-5-(4-methoxyphenyl)-2,4-decadienoic acid, mp 126°-127.5° C. | CCCCC/C(=C\C=C\C(=O)O)c1ccc(OC)cc1 | null | 81 | null |
293,478 | ord_dataset-b90b48a6c23149a1aa2d91b92b1a31e4 | null | 1994-01-01T00:07:00 | true | C[O:2][C:3](=[O:30])[C@:4]([C:20]1[CH:29]=[CH:28][C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[N:21]=1)([CH3:19])[NH:5][C:6]([O:8][CH:9]1[CH:16]2[CH2:17][CH:12]3[CH2:13][CH:14]([CH2:18][CH:10]1[CH2:11]3)[CH2:15]2)=[O:7]>CCCCC>[CH:10]12[CH2:18][CH:14]3[CH2:13][CH:12]([CH2:17][CH:16]([CH2:15]3)[CH:9]1[O:8][C:6]([NH:5][C@:4]([C:20]1[CH:29]=[CH:28][C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[N:21]=1)([C:3]([OH:30])=[O:2])[CH3:19])=[O:7])[CH2:11]2 | COC(=O)[C@](C)(NC(=O)OC1C2CC3CC(C2)CC1C3)c1ccc2ccccc2n1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCCCC | null | null | null | null | null | null | null | null | null | null | null | null | Method was as described for Example 30, Step 5, but using N-(2-adamantyloxy-carbonyl)-2-(quinolin-yl)-alanine methyl ester (3.5 g, 8.3 mmol) to obtain N-(2-adamantyloxy-carbonyl)-2-(quinolin-yl)-alanine (2.0 g, 59.0%) as a beige solid from n-pentane. | C[C@](NC(=O)OC1C2CC3CC(C2)CC1C3)(C(=O)O)c1ccc2ccccc2n1 | null | 61.1 | null |
94,333 | ord_dataset-62e11cab5a6e47d89878616c244e20ef | null | 1982-01-01T00:05:00 | true | [C:1]([O:4][C@@H:5]1[CH2:10][C@H:9]2[C@H:11]3[C@H:21]([CH2:22][CH2:23][C@:7]2([CH3:8])[C@H:6]1[N:25]([CH3:32])[C:26](=[O:31])[C:27]([F:30])([F:29])[F:28])[C@:19]1([CH3:20])[C:14](=[CH:15][C:16](=[O:24])[CH2:17][CH2:18]1)[CH2:13][CH2:12]3)(=[O:3])[CH3:2].C1(C)C=CC=CC=1>ClC1C=CC=CC=1>[C:1]([O:4][C@@H:5]1[CH2:10][C@H:9]2[C@H:11]3[C@H:21]([CH2:22][CH2:23][C@:7]2([CH3:8])[C@H:6]1[N:25]([CH3:32])[C:26](=[O:31])[C:27]([F:29])([F:28])[F:30])[C@:19]1([CH3:20])[C:14](=[CH:15][C:16](=[O:24])[CH:17]=[CH:18]1)[CH2:13][CH2:12]3)(=[O:3])[CH3:2] | CC(=O)O[C@@H]1C[C@H]2[C@@H]3CCC4=CC(=O)CC[C@]4(C)[C@H]3CC[C@]2(C)[C@H]1N(C)C(=O)C(F)(F)F | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Clc1ccccc1 | Cc1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | A solution of 16α-acetyloxy-17β-(N-trifluoroacetyl-methylamino)-androst-4-en-3-one (1.88 g) and diphenylselenic anhydride (1.7 g) in chlorobenzene (39 ml) was heated under reflux for 1 h. The solution was cooled, toluene was added and the solution was filtered through a column (7.5 cm×2.5 cm) of silica gel (0.063-0.2 mm). Elution with toluene removed diphenylselenide. Elution with ether yielded a fraction which was evaporated to dryness to give 16α-acetyloxy-17β-(N-trifluoroacetyl-methylamino)-androsta-1,4-dien-3-one as a yellow gum (1.52 g). A solution of the product in ethanol (40 ml) and aqueous sodium hydroxide solution (3 ml; 4 N) was heated under reflux for 1.5 h.; the solution was concentrated and cooled, then water was added to precipitate an off-white solid, which was filtered off, washed with water and dried in vacuo to give 16α-hydroxy-17β-methylamino-androsta-1,4-dien-3-one (1 g). The product was dissolved in ethanol (20 ml), a solution of maleic acid (0.37 g) in ethanol (10 ml) was added and the resulting solution was treated with charcoal, filtered and evaporated to give a pale yellow gum (1.44 g). Crystallisation from acetone gave 16α-hydroxy-17β-methylamino-androsta-1,4-dien-3-one (Z)-2-butenedioate (1:1) (salt) as colourless prisms (0.88 g), m.p. 184°-191° C. (decomp.), [α]D +14.2° (c 0.88 in ETOH). | CC(=O)O[C@@H]1C[C@H]2[C@@H]3CCC4=CC(=O)C=C[C@]4(C)[C@H]3CC[C@]2(C)[C@H]1N(C)C(=O)C(F)(F)F | null | 81.2 | null |
1,333,632 | ord_dataset-cfad8b3f00044bcda60a96b019f09872 | null | 2013-01-01T00:08:00 | true | [F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[N:9]1[CH:13]=[C:12](I)[N:11]=[CH:10]1.C([Mg]Cl)(C)C.[CH2:20]([Sn:24](Cl)([CH2:29][CH2:30][CH2:31][CH3:32])[CH2:25][CH2:26][CH2:27][CH3:28])[CH2:21][CH2:22][CH3:23].[NH4+].[Cl-]>O1CCCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[N:9]1[CH:13]=[C:12]([Sn:24]([CH2:25][CH2:26][CH2:27][CH3:28])([CH2:29][CH2:30][CH2:31][CH3:32])[CH2:20][CH2:21][CH2:22][CH3:23])[N:11]=[CH:10]1 | Fc1ccc(F)c(-n2cnc(I)c2)c1 | CCCC[Sn](Cl)(CCCC)CCCC | null | CC(C)[Mg]Cl | [Cl-] | [NH4+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | null | 1.5 | A solution of 1-(2,5-difluorophenyl)-4-iodo-1H-imidazole (0.115 g, 0.38 mmol) in 2 mL of tetrahydrofuran was chilled in an ice/water bath 5 min. Isopropylmagnesium chloride solution (2.0 M in tetrahydrofuran, 0.190 mL, 0.38 mmol) was added all at once. The bath was removed, and the pale yellow solution stirred 1.5 h. Tributyltin chloride (0.105 mL, 0.39 mmol) was added all at once, and the pale yellow solution was stirred 1.5 h. A sat. aq. NH4Cl solution (10 mL) was added, and the mixture was extracted with two 10 mL portions of ethyl acetate. The combined organic layers were washed with 20 mL of a sat. aq. NaCl solution, dried over Na2SO4, filtered and concentrated to provide 0.198 g of 1-(2,5-difluoro-phenyl)-4-tributylstannanyl-1H-imidazole as a yellow oil which was used without further purification. MS: (M+H)+=471. | CCCC[Sn](CCCC)(CCCC)c1cn(-c2cc(F)ccc2F)cn1 | null | 111.1 | null |
845,790 | ord_dataset-e2b35e721c2741999b0005d12691f9fe | null | 2008-01-01T00:10:00 | true | C(OC(=O)[NH:10][CH2:11][C:12]1[NH:13][C:14]2[C:19]([CH:20]=1)=[CH:18][CH:17]=[C:16]([OH:21])[CH:15]=2)C1C=CC=CC=1.C([O-])([O-])=O.[Cs+].[Cs+].Cl[CH:30]([C:36]([O:38][CH2:39][CH3:40])=[O:37])[C:31]([O:33][CH2:34][CH3:35])=[O:32]>CC(C)=O.C(OCC)(=O)C>[CH2:34]([O:33][C:31](=[O:32])[CH:30]([O:21][C:16]1[CH:15]=[C:14]2[C:19]([CH:20]=[C:12]([CH2:11][NH2:10])[NH:13]2)=[CH:18][CH:17]=1)[C:36]([O:38][CH2:39][CH3:40])=[O:37])[CH3:35] | O=C(NCc1cc2ccc(O)cc2[nH]1)OCc1ccccc1 | CCOC(=O)C(Cl)C(=O)OCC | null | O=C([O-])[O-] | [Cs+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(C)=O | CCOC(C)=O | null | null | null | null | null | null | null | null | null | null | 8 | (6-Hydroxy-1H-indol-2-ylmethyl)-carbamic acid benzyl ester was dissolved in 10 ml acetone, Cs2CO3 and diethyl chloromalonate were added. The reaction is stirred overnight. HPLC and TLC indicated the reaction is done. The mixture was diluted with ethyl acetate and filtered through silica gel plug. The filtrate is concentrated and redissolved in ethanol, hydrogenated for 3 hours at 40 psi of hydrogen. The mixture is filtered, washed with ethyl acetate. The filtrate is concentrated to give 2-(2-Aminomethyl-1H-indol-6-yloxy)-malonic acid diethyl ester. | CCOC(=O)C(Oc1ccc2cc(CN)[nH]c2c1)C(=O)OCC | null | null | null |
868,815 | ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b | null | 2009-01-01T00:03:00 | true | [C:1]([C:3]([C:24]#[N:25])=[C:4]([N:11]1[CH2:16][CH2:15][N:14](C(OC(C)(C)C)=O)[CH2:13][CH2:12]1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)#[N:2]>C(O)(C(F)(F)F)=O.C(Cl)Cl>[C:5]1([C:4]([N:11]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)=[C:3]([C:1]#[N:2])[C:24]#[N:25])[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1 | CC(C)(C)OC(=O)N1CCN(C(=C(C#N)C#N)c2ccccc2)CC1 | 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 | null | 16 | tert-Butyl 4-(2,2-dicyano-1-phenylvinyl)piperazine-1-carboxylate (2 g) was dissolved in a 33.3% solution of TFA in methylene chloride (20 ml). After 16 hour at room temperature, solvents were removed under vacuum to offer a residue which was purified using silica gel chromatography to give 2-(phenyl(piperazin-1-yl)methylene)malononitrile (1 g). 1H NMR (500 MHz, CD3OD) □7.62 (m, 5H), 3.70 (b, 4H), 3.47 (b, 4H); 13C NMR (125 MHz, CD3OD) □172.9, 132.7, 132.5, 129.6, 116.6, 116.0, 55.2, 43.4. MS m/z: (M+H)+ calcd for C14H15N4 239.13, found 239.13. Retention time 0.56 min (column A). | N#CC(C#N)=C(c1ccccc1)N1CCNCC1 | null | 71 | null |
1,752,496 | ord_dataset-97eb2ab57fec4160922caae33b54d956 | null | 2016-01-01T00:08:00 | true | [NH2:1][CH2:2][C@H:3]1[CH2:8][CH2:7][CH2:6][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4]1.Br[C:17]1[C:18]([NH2:24])=[N:19][CH:20]=[C:21]([Br:23])[N:22]=1.CCN(CC)CC>CS(C)=O>[NH2:24][C:18]1[C:17]([NH:1][CH2:2][C@H:3]2[CH2:8][CH2:7][CH2:6][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4]2)=[N:22][C:21]([Br:23])=[CH:20][N:19]=1 | Nc1ncc(Br)nc1Br | CC(C)(C)OC(=O)N1CCC[C@H](CN)C1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CS(C)=O | CCN(CC)CC | null | null | null | null | null | null | null | null | null | 130 | 8 | (R)-tert-butyl 3-(aminomethyl)piperidine-1-carboxylate (4.97 g, 22.40 mmol) was dissolved in DMSO (80 ml), and then 3,5-dibromopyrazine-2-amine (8.5 g, 33.60 mmol) and Et3N (6.3 ml) were added, followed by stirring at 130° C. overnight. After the completion of the reaction, the reaction mixture was extracted with H2O, EA, and brine, followed by drying (Na2SO4), filtration, and concentration under reduced pressure, and the residue was purified by column chromatography (EA:Hex=1:1), to give (R)-tert-butyl 3-(((3-amino-6-bromopyrazine-2-yl)amino)methyl)piperidine-1-carboxylate (2.19 g, two steps: 26%). | CC(C)(C)OC(=O)N1CCC[C@H](CNc2nc(Br)cnc2N)C1 | null | 25.3 | null |
196,391 | ord_dataset-a58d1baeeea441fb9918c10f18f2cdb9 | null | 1989-01-01T00:09:00 | true | C(C1[CH:13]=[CH:12][C:6]([NH:7][S:8]([CH3:11])(=[O:10])=[O:9])=[C:5]([O:14][C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=2[F:22])[CH:4]=1)#N.Cl.[C:24]([OH:27])(=[O:26])[CH3:25]>>[F:22][C:16]1[CH:17]=[C:18]([F:21])[CH:19]=[CH:20][C:15]=1[O:14][C:5]1[CH:4]=[C:25]([CH:13]=[CH:12][C:6]=1[NH:7][S:8]([CH3:11])(=[O:9])=[O:10])[C:24]([OH:27])=[O:26] | CC(=O)O | CS(=O)(=O)Nc1ccc(C#N)cc1Oc1ccc(F)cc1F | 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 | A mixture of 4'-cyano-2'-(2,4-difluorophenoxy)methanesulfonanilide (1.3 g) and concentrated hydrochloric acid (13 ml) in acetic acid (8 ml) was refluxed for 8 hours. The precipitates were filtered, washed with water, dried, and recrystallized from a mixture of ethyl acetate and hexane to give crystals of 3-(2,4-difluorophenoxy)-4-(methanesulfonamido)benzoic acid (0.72 g). | CS(=O)(=O)Nc1ccc(C(=O)O)cc1Oc1ccc(F)cc1F | null | null | null |
780,214 | ord_dataset-8034115bd2ec4d3e95bd3ff7cfde0bde | null | 2007-01-01T00:07:00 | true | [OH:1][CH:2]1[CH:7]2[CH2:8][CH2:9][N:4]([CH2:5][CH2:6]2)[CH2:3]1.I[C:11]1[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][CH:12]=1>>[N+:17]([C:14]1[CH:15]=[CH:16][C:11]([O:1][CH:2]2[CH:7]3[CH2:8][CH2:9][N:4]([CH2:5][CH2:6]3)[CH2:3]2)=[CH:12][CH:13]=1)([O-:19])=[O:18] | O=[N+]([O-])c1ccc(I)cc1 | OC1CN2CCC1CC2 | null | null | null | null | null | null | null | 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-Hydroxy quinuclidine (Aldrich, 2.54 g, 10 mmol) was treated with 1-iodo-4-nitro-benzene (5 g, 20 mmol) according to the procedure of Example 14A. The title compound was purified by chromatography (SiO2, CH2Cl2:MeOH:NH3.H2O, 90:10:1, Rf. 0.20) (1.02 g, yield, 21%). 1H NMR (MeOH-d4, 300 MHz) δ 1.40–1.56 (m, 1H), 1.65–1.90 (m, 2H), 1.90–2.08 (m, 1H), 2.15–2.25 (m, 1H), 2.75–3.00 (m, 5H), 3.34–3.40 (m, 1H), 4.69 (m, 1H), 7.07 (d, J=9.5 Hz, 2H), 8.21 (d, J=9.2, Hz, 2H) ppm. MS (DCl/NH3) m/z 249 (M+H)+. | O=[N+]([O-])c1ccc(OC2CN3CCC2CC3)cc1 | null | null | null |
129,860 | ord_dataset-2f37329a4b254471a74f2eb0981f11ec | null | 1985-01-01T00:05:00 | true | Cl.[C:2]([O:5][CH:6]1[CH2:14][CH2:13][CH:12]2[CH:7]1[CH2:8][CH:9]=[C:10]([O:15]C)[CH2:11]2)(=[O:4])[CH3:3]>CO>[C:2]([O:5][CH:6]1[CH2:14][CH2:13][CH:12]2[CH:7]1[CH2:8][CH2:9][C:10](=[O:15])[CH2:11]2)(=[O:4])[CH3:3] | COC1=CCC2C(CCC2OC(C)=O)C1 | 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 | 0.08 | Concentrated hydrochloric acid (3.5 ml) was added to a solution of 7-acetoxy-3-methoxybicyclo[4,3,0]non-3-ene (58.9 g; prepared as described in Reference Example 3) in methanol (500 ml), and the mixture was stirred at the ambient temperature for 5 minutes. It was then concentrated under reduced pressure, to give 7-acetoxybicyclo[4,3,0]nonan-3-one (54.7 g). | CC(=O)OC1CCC2CC(=O)CCC21 | null | 99.5 | null |
1,254,228 | ord_dataset-c544c0c663f54dbea4ddb52ddde7934e | null | 2013-01-01T00:01:00 | true | [CH3:1][C:2]1[C:7]([N+:8]([O-])=O)=[CH:6][CH:5]=[C:4]([C:11]([S:14]([CH3:17])(=[O:16])=[O:15])([CH3:13])[CH3:12])[N:3]=1>C(O)(=O)C.[Zn]>[CH3:1][C:2]1[C:7]([NH2:8])=[CH:6][CH:5]=[C:4]([C:11]([S:14]([CH3:17])(=[O:16])=[O:15])([CH3:13])[CH3:12])[N:3]=1 | Cc1nc(C(C)(C)S(C)(=O)=O)ccc1[N+](=O)[O-] | null | null | [Zn] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(=O)O | null | null | null | null | null | null | null | null | null | null | 25 | 1 | To a solution of 2-methyl-6-(2-(methylsulfonyl)propan-2-yl)-3-nitropyridine (1.27 g, 4.92 mmol) in 50 mL acetic acid, zinc dust (1.6 g, 24.5 mmol) was added in small portions under ice-cooling. After 1 h, more zinc dust (ca. 2 g, 31 mmol) was added in small portions and mixture was stirred at room temperature for another hour. Solids were filtered off, washed with CH3CN, and filtrate was concentrated. Residue was purified by CC(CH2Cl2/MeOH 20:1+1% NEt3). Fractions containing product were concentrated and re-purified by HPLC. Fractions containing product were partly concentrated and residue was extracted with 1M NaHCO3 and CH2Cl2. Organic phases were dried over MgSO4, filtered and concentrated to give 2-methyl-6-(2-(methylsulfonyl)propan-2-yl)pyridin-3-amine (0.664 g, 59% yield) as a white solid. 1HNMR (CDCl3, 400 MHz) δ 1.84 (s, 6H), 2.39 (s, 3H), 2.76 (s, 3H), 3.68 (s, 2H), 6.92-6.94 (d, J=8.3 Hz, 1H), 7.29-7.31 (d, J=8.3 Hz, 1H). Exact mass calculated for C10H16N2O2S 228.09 found 229.2 (MH+). | Cc1nc(C(C)(C)S(C)(=O)=O)ccc1N | null | 59.1 | null |
609,719 | ord_dataset-73916d628db147c89020b3baac642d48 | null | 2003-01-01T00:09:00 | true | C([O:5][C@@H:6]1[C@@H:10]([O:11]C(=O)CC)[C@@H:9]([C@@H:16]([CH2:22][O:23]C(=O)CC)[O:17]C(=O)CC)[O:8][C@H:7]1[N:28]1[CH:35]=[CH:34][C:32](=[O:33])[NH:31][C:29]1=[O:30])(=O)CC>CO.N>[C@@H:7]1([N:28]2[CH:35]=[CH:34][C:32](=[O:33])[NH:31][C:29]2=[O:30])[O:8][C@H:9]([C@@H:16]([CH2:22][OH:23])[OH:17])[C@H:10]([OH:11])[C@H:6]1[OH:5] | CCC(=O)OC[C@@H](OC(=O)CC)[C@H]1O[C@@H](n2ccc(=O)[nH]c2=O)[C@H](OC(=O)CC)[C@H]1OC(=O)CC | null | null | N | 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 | 8 | 1-(2,3,5,6-Tetra-O-propanoyl-β-D-glucofuranosyl)uracil was dissolved in methanol saturated with ammonia (15 mL) and left at room temperature overnight. After concentrating in vacuo, the resulting residue was purified by flash silica chromatography, eluting with CHCl3/CH3OH/NH3 aq. (84:15:1), to give 1-βD-glucofuranosyluracil as a colourless solid (680 mg, 75%). A sample was recrystallised from EtOH to give the product as colourless needles, mp 175-176.5° C. (from EtOH), [α]D21=+9.91 (c 1.1 in H2O), (Found: C, 44.0; H, 5.0; N, 10.35. C10H14N2O7 requires C, 43.8; H, 5.15; N, 10.2%); δH (D2O) 7.82 (1H, d, J 8.1, 6-H), 5.79 (1H, d, J 8.1, 5-H), 5.75 (1H, s, 1′-H), 4.27-4.25 (2H, m, 2′- and 3′-H), 4.23 (1H, dd, J 8.6 and 2.7, 4′-H), 4.12 (1H, ddd, J 8.6, 5.4 and 2.7, 5′-H), 3.86 (1H, dd, J 12.1 and 2.7, 6′a-H), 3.37 (1H, dd, J 12.1 and 5.4, 6′b-H); δC (D2O) 166.8 (3-C), 151.9 (2-C), 142.6 (6-C), 101.5 (5-C), 92.4 (1′-C), 82.8 (4′-C), 80.7, 74.7 (2′- and 3′-C), 68.9 (5′-C), 63.8 (6′-C); m/z (FAB) 275.088448 (MH+, C10H15N2O7 requires 275.087926). | O=c1ccn([C@@H]2O[C@H]([C@H](O)CO)[C@H](O)[C@H]2O)c(=O)[nH]1 | null | 75 | null |
366,594 | ord_dataset-b18df02d6e9345faa0f2dae281a0870a | null | 1997-01-01T00:06:00 | true | [C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([C:11]([NH:13][C:14]3[CH:28]=[CH:27][C:17]([O:18][CH2:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[CH:16][CH:15]=3)=[O:12])=[CH:8][C:7]=2[CH:29]=1)#[N:2].[SH2:30]>N1C=CC=CC=1.C(N(CC)CC)C>[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([C:11]([NH:13][C:14]3[CH:28]=[CH:27][C:17]([O:18][CH2:19][C:20]([O:22][C:23]([CH3:24])([CH3:25])[CH3:26])=[O:21])=[CH:16][CH:15]=3)=[O:12])=[CH:8][C:7]=2[CH:29]=1)(=[S:30])[NH2:2] | S | CC(C)(C)OC(=O)COc1ccc(NC(=O)c2cc3cc(C#N)ccc3o2)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | c1ccncc1 | CCN(CC)CC | null | null | null | null | null | null | null | null | null | null | 18 | t-Butyl 4-[(5-cyano-2-benzofuranyl)carbonylamino]phenoxyacetate (430 mg, 1.10 mmol) was dissolved in a mixed solution of pyridine (30 ml) and triethylamine (7 ml), and hydrogen sulfide gas was blown in for 10 minutes at room temperature, which was followed by stirring for 18 hours. Low boiling matters were distilled away from the reaction mixture under reduced pressure and the residue was dissolved in ethyl acetate. The mixture was washed with a 2N aqueous potassium hydrogensulfate solution, water and saturated brine, and dried over anhydrous magnesium sulfate. After filtration, low boiling matters were distilled away from the filtrate under reduced pressure to give t-butyl 4-[(5-thiocarbamoyl-2-benzofuranyl)carbonylamino]phenoxyacetate as a yellow solid. The solid was dissolved in acetone (50 ml) and methyl iodide (2 ml) was added. The mixture was refluxed under heating for 40 minutes. Low boiling matters were distilled away from the reaction mixture under reduced pressure to give t-butyl 4-[[5-[(1-methylthio)iminomethyl]-2-benzofuranyl)carbonylamino]phenoxyacetate as a yellow solid. Thereto were added methanol (30 ml) and ammonium acetate (280 mg, 3.64 mmol), and the mixture was refluxed under heating for 3 hours. Low boiling matters were distilled away from the reaction mixture under reduced pressure and the residue was purified by silica gel column chromatography (chloroform/methanol=100/3-3/1) to give 596 mg of hydriodide of compound (8) as a yellow solid (quantitatively in 3 steps). | CC(C)(C)OC(=O)COc1ccc(NC(=O)c2cc3cc(C(N)=S)ccc3o2)cc1 | null | null | null |
1,389,915 | ord_dataset-31641fb65b34430fa7435229b949b604 | null | 2014-01-01T00:01:00 | true | [F:1][C:2]1[CH:38]=[CH:37][C:5]([CH2:6][O:7][C:8]2[CH:13]=[CH:12][N:11]([C:14]3[CH:15]=[CH:16][C:17]4[C:18]5[CH2:28][CH2:27][N:26](C(OC(C)(C)C)=O)[CH2:25][CH2:24][C:19]=5[N:20]([CH3:23])[C:21]=4[CH:22]=3)[C:10](=[O:36])[CH:9]=2)=[CH:4][CH:3]=1.[ClH:39]>ClCCl>[ClH:39].[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][O:7][C:8]2[CH:13]=[CH:12][N:11]([C:14]3[CH:15]=[CH:16][C:17]4[C:18]5[CH2:28][CH2:27][NH:26][CH2:25][CH2:24][C:19]=5[N:20]([CH3:23])[C:21]=4[CH:22]=3)[C:10](=[O:36])[CH:9]=2)=[CH:37][CH:38]=1 | Cn1c2c(c3ccc(-n4ccc(OCc5ccc(F)cc5)cc4=O)cc31)CCN(C(=O)OC(C)(C)C)CC2 | null | null | Cl | 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 | To a solution of tert-butyl 8-(4-(4-fluorobenzyloxy)-2-oxopyridin-1(2H)-yl)-6-methyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate (120 mg, 0.23 mmol) in dichloromethane (1.0 mL) was added HCl (2M in diethyl ether, 5.0 mL). The resulting slurry was stirred at room temperature overnight and concentrated under reduced pressure to afford the title compound (85 mg, 82%) as a yellow solid: 1H NMR (500 MHz, CD3OD) δ 7.59 (d, J=8.5 Hz, 2H), 7.50 (dd, J=8.0, 5.5 Hz, 2H), 7.40 (s, 1H), 7.15 (t, J=8.5 Hz, 2H), 7.01 (d, J=8.5 Hz, 1H), 6.30 (t, J=6.5 Hz, 1H), 6.14 (br s, 1H), 5.16 (s, 2H), 3.74 (s, 3H), 3.54 (t, J=5.5 Hz, 2H), 3.48 (t, J=5.5 Hz, 2H), 3.34 (t, J=5.5 Hz, 2H), 3.24 (t, J=5.5 Hz, 2H); ESI MS m/z 418 [M+H]+. | Cn1c2c(c3ccc(-n4ccc(OCc5ccc(F)cc5)cc4=O)cc31)CCNCC2 | null | 82 | null |
488,537 | ord_dataset-37b0416f244344a08cf357e851eedf2a | null | 2001-01-01T00:01:00 | true | [CH:1]1([CH:4]([O:6][CH2:7][C:8]([OH:10])=[O:9])[CH3:5])[CH2:3][CH2:2]1.O[C:12]([CH3:27])([CH2:25][CH3:26])[C:13]([C:15]1[CH:20]=[CH:19][C:18]([S:21]([CH3:24])(=[O:23])=[O:22])=[CH:17][CH:16]=1)=[O:14]>>[CH3:27][C@@:12]([O:9][C:8](=[O:10])[CH2:7][O:6][CH:4]([CH:1]1[CH2:3][CH2:2]1)[CH3:5])([CH2:25][CH3:26])[C:13]([C:15]1[CH:20]=[CH:19][C:18]([S:21]([CH3:24])(=[O:23])=[O:22])=[CH:17][CH:16]=1)=[O:14] | CCC(C)(O)C(=O)c1ccc(S(C)(=O)=O)cc1 | CC(OCC(=O)O)C1CC1 | null | null | null | null | null | null | null | 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 described in Example 134 Step 2 using (1-cyclopropylethoxy)acetic acid and 2(R) 2-hydroxy-2-methyl-1-(4-(methylsulfonyl)phenyl)butan-1-one from Example 117, Step 3. | CC[C@@](C)(OC(=O)COC(C)C1CC1)C(=O)c1ccc(S(C)(=O)=O)cc1 | null | null | null |
443,485 | ord_dataset-ba7561dae3884c07a8beddd0b9f1222e | null | 1999-01-01T00:10:00 | true | [CH:1]([C:3]1[CH:17]=[CH:16][CH:15]=[CH:14][C:4]=1[CH:5]([C:8]1[S:12][CH2:11][N:10]([CH3:13])[CH:9]=1)[O:6][CH3:7])=O.[F:18][C:19]([F:31])([F:30])[C:20]1[CH:25]=[CH:24][C:23]([C:26](=[N:28][NH2:29])[CH3:27])=[CH:22][CH:21]=1>CO>[CH3:7][O:6][CH:5]([C:8]1[S:12][CH2:11][N:10]([CH3:13])[CH:9]=1)[C:4]1[CH:14]=[CH:15][CH:16]=[CH:17][C:3]=1[CH:1]=[N:29][N:28]=[C:26]([C:23]1[CH:24]=[CH:25][C:20]([C:19]([F:18])([F:31])[F:30])=[CH:21][CH:22]=1)[CH3:27] | COC(C1=CN(C)CS1)c1ccccc1C=O | CC(=NN)c1ccc(C(F)(F)F)cc1 | 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 | 25 | 3 | To 0.23 g (1 mmol) of 5-(2-formyl-α-methoxybenzyl)-3-methylthiazole in 2 ml of methanol was added 0.22 g (1.1 mmol) of 4'-(trifluoromethyl)acetophenone hydrazone and stirred at room temperature for 3 hours. After completion of the reaction, methanol was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (ethyl acetate/n-hexane) to give 5-[α-methoxy-2-{4-(4-trifluoromethylphenyl)-2,3-diaza-1,3-pentadienyl}benzyl]-3-methylthiazole (0.23 g, 55.4%) as oil. | COC(C1=CN(C)CS1)c1ccccc1C=NN=C(C)c1ccc(C(F)(F)F)cc1 | null | 53.1 | null |
791,544 | ord_dataset-744b04e8228742eb9aa4bde36f5dedf1 | null | 2007-01-01T00:10:00 | true | [OH:1][C@@H:2]([CH2:6][CH:7]([CH3:9])[CH3:8])[C:3]([OH:5])=[O:4].[H-].[Na+].I[CH2:13][CH2:14][CH2:15][CH2:16][CH3:17].O>CN(C=O)C>[CH3:8][CH:7]([CH3:9])[CH2:6][C@H:2]([O:1][CH2:3][CH2:2][CH2:6][CH2:7][CH3:8])[C:3]([O:5][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])=[O:4] | CC(C)C[C@H](O)C(=O)O | CCCCCI | null | [H-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | 0.33 | To a solution of (2S)-2-hydroxy-4-methylpentanoic acid 8 (1 g, 7.6 mmol) in 50 mL DMF at 0° C. was added NaH (0.6 g, 15.2 mmol) and stirred for 20 min, followed by the addition of iodopentane (1.5 g, 7.6 mmol). The reaction mixture was stirred at rt for additional 16 h. The solution was poured into water and the layers separated. The aqueous layer was extracted with methylene chloride and the combined extracts were washed with sat'd NaHCO3, dried over magnesium sulfate, and concentrated to a crude product. Upon further purification, compound 9 was obtained as an oil (80 mg, 4%). MS [M+H]+ 273. Step 2: Preparation of (2S)-4-methyl-2-pentyloxypentanoic acid 10. To a solution of (2S)-pentyl 4-methyl-2-pentyloxypentanoate 9 (80 mg, 0.3 mmol) in 20 mL of THF cooled to 0° C. was added dropwise a solution of lithium hydroxide monohydrate (25 mg, 0.6 mmol) in 5 mL of water. The reaction mixture was stirred at rt for 16 h. THF was removed under reduced pressure to give an yellow oil which was diluted with 10 mL of 1 N HCl. The aqueous phase was extracted with CH2Cl2 (8×15 mL), and the extracts were combined, dried over Na2SO4, and concentrated to afford compound 10 (45 mg, 74%). MS [M+H]+ 203. Step 3: Preparation of (7S)-[(2S)-1-oxo-2-pentyloxy-(4-methylpentyl)]amino-5-methyl-5H,7H-dibenzo[b,d]azepin-6-one, 12. To a solution of (2S)-4-methyl-2-pentyloxypentanoic acid 10 (45 mg, 0.22 mmol) in CH2Cl2/DMF (5:1, 15 mL) at 0° C. was added HOBT (40 mg, 0.26 mmol) and EDC (50 mg, 0.26 mmol). The mixture was stirred for 10 min then the amine 11 (52 mg, 0.22 mmol) was added and stirring was continued for 1 h. The solution was poured into water and the layers separated. The aqueous layer was extracted with methylene chloride and the combined extracts were washed with water, 1 N HCl, sat'd NaHCO3, dried over magnesium sulfate, and concentrated to a glassy solid compound 12 (80 mg, 86%). MS [M+H]+ 423. | CCCCCOC(=O)[C@H](CC(C)C)OCCCCC | null | null | null |
786,187 | ord_dataset-4ad5db8537994579bef51f16dd8bf0bd | null | 2007-01-01T00:08:00 | true | [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]2[O:10][C:11]([CH3:30])=[C:12]([CH2:14][O:15][C@@H:16]3[CH2:21][CH2:20][CH2:19][C@H:18]([CH2:22][CH:23]=[CH:24][C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH2:17]3)[N:13]=2)[CH:6]=[CH:7][CH:8]=1>CO.[Pd]>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]2[O:10][C:11]([CH3:30])=[C:12]([CH2:14][O:15][C@@H:16]3[CH2:21][CH2:20][CH2:19][C@H:18]([CH2:22][CH2:23][CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH2:17]3)[N:13]=2)[CH:6]=[CH:7][CH:8]=1 | CCOC(=O)C=CC[C@H]1CCC[C@@H](OCc2nc(-c3cccc(OC)c3)oc2C)C1 | null | null | [Pd] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | 25 | 7 | 190 mg of ethyl 4-{cis-3-[2-(3-methoxyphenyl)-5-methyloxazol-4-yl-methoxy]cyclohexyl}but-2-enoate are dissolved in 25 ml of methanol, and 20 mg of Pd (10% on activated carbon) are added. The mixture is stirred at room temperature and under an atmosphere of hydrogen for 7 hours. The catalyst is filtered off through Celite and the filtrate is concentrated under reduced pressure. This gives 110 mg of ethyl 4-{cis-3-[2-(3-methoxyphenyl)-5-methyloxazol-4-ylmethoxy]cyclohexyl}butyrate as an oil. C24H33NO5 (415.53), MS(ESI): 416 (M+H+). | CCOC(=O)CCC[C@H]1CCC[C@@H](OCc2nc(-c3cccc(OC)c3)oc2C)C1 | null | null | null |
1,254,328 | ord_dataset-c544c0c663f54dbea4ddb52ddde7934e | null | 2013-01-01T00:01:00 | true | Cl.[CH3:2][O:3][C:4](=[O:46])[NH:5][C@H:6]([C:10]([N:12]1[CH2:16][CH2:15][CH2:14][C@H:13]1[C:17]1[NH:18][CH:19]=[C:20]([C:22]2[CH:27]=[CH:26][C:25]([C:28]3[C:29]4[S:35][CH:34]=[C:33]([C:36]5[NH:37][C:38]([C@@H:41]6[CH2:45][CH2:44][CH2:43][NH:42]6)=[N:39][CH:40]=5)[C:30]=4[S:31][CH:32]=3)=[CH:24][CH:23]=2)[N:21]=1)=[O:11])[CH:7]([CH3:9])[CH3:8].[C:47]([O:51][C:52]([NH:54][C@H:55]([C:66]1[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=1)[C:56](N1CCC[C@H]1C(O)=O)=[O:57])=[O:53])(C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC>CN(C)C=O>[CH3:2][O:3][C:4](=[O:46])[NH:5][C@H:6]([C:10]([N:12]1[CH2:16][CH2:15][CH2:14][C@H:13]1[C:17]1[NH:18][CH:19]=[C:20]([C:22]2[CH:27]=[CH:26][C:25]([C:28]3[C:29]4[S:35][CH:34]=[C:33]([C:36]5[NH:37][C:38]([C@@H:41]6[CH2:45][CH2:44][CH2:43][N:42]6[C:56](=[O:57])[C@H:55]([NH:54][C:52]([O:51][CH3:47])=[O:53])[C:66]6[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=6)=[N:39][CH:40]=5)[C:30]=4[S:31][CH:32]=3)=[CH:24][CH:23]=2)[N:21]=1)=[O:11])[CH:7]([CH3:9])[CH3:8] | COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1nc(-c2ccc(-c3csc4c(-c5cnc([C@@H]6CCCN6)[nH]5)csc34)cc2)c[nH]1)C(C)C | CC(C)(C)OC(=O)N[C@@H](C(=O)N1CCC[C@H]1C(=O)O)c1ccccc1 | null | CN(C)C(On1nnc2cccnc21)=[N+](C)C | Cl | 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 | CCN(CC)CC | null | null | null | null | null | null | null | null | null | 25 | 12 | To a mixture of compound 71 (0.078 mmol), compound 33 (0.085 mmol), and HATU (0.085 mmol) in dimethylformamide (1 mL) was added Et3N (0.465 mmol) dropwise. The reaction mixture was stirred at room temperature during 12 hrs. The solvent was removed under reduced pressure and the residue was dissolved in methanol. This mixture was eluted through a SCX-2 column. The filtrate was concentrated and the residue was purified by semi-preparative HPLC to give compound A200 as a white solid in 25% yield. 1H NMR (DMSO-d6, 400 MHz) δ (ppm) 0.85 (d, J=6.46 Hz, 3H), 0.91 (d, J=6.64 Hz, 3H), 1.84-2.20 (m, 8H), 3.11-3.22 (m, 1H), 3.35-3.38 (m, 1H), 3.51-3.54 (m, 6H), 3.77-3.92 (m, 2H), 4.04-4.09 (m, 1H), 5.06-5.11 (m, 2H), 5.48-5.52 (m, 1H), 6.88-8.40 (m, 13H), 11.80-11.87 (m, 1H); MS (ESI, EI+) m/z=835.4 (MH+). | COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1nc(-c2ccc(-c3csc4c(-c5cnc([C@@H]6CCCN6C(=O)[C@H](NC(=O)OC)c6ccccc6)[nH]5)csc34)cc2)c[nH]1)C(C)C | null | 25 | null |
1,750,491 | ord_dataset-60a3e71da3174666a50a61dcfa611a9f | null | 2016-01-01T00:07:00 | true | [C:1]([BH3-])#N.[Na+].Cl.[S:6]1[C:14]2[CH2:13][CH2:12][NH:11][CH2:10][C:9]=2[CH:8]=[CH:7]1.C=O>ClCCl>[CH3:1][N:11]1[CH2:12][CH2:13][C:14]2[S:6][CH:7]=[CH:8][C:9]=2[CH2:10]1 | [BH3-]C#N | c1cc2c(s1)CCNC2 | null | C=O | Cl | [Na+] | 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 | 16 | Sodium cyanoborohydride (10 g, 160 mmol) was slowly added to a mixture of 4,5,6,7-tetrahydrothieno[3,2-c]pyridine hydrochloride (7.0 g, 40.0 mmol) and formaldehyde (35% in water, 10 mL) in dichloromethane (100 mL) at room temperature. The resulting mixture was stirred at room temperature for 16 h. Work-up: the reaction mixture was partitioned between ethyl acetate (300 mL) and water (200 mL). The organic layer was separated, washed with brine (100 mL), dried over Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography on silica gel (EtOAc/petroleum ether=1:5˜1:1) to afford the title compound as a white solids (2.0 g, 33%). 1H NMR (DMSO-d6, 400 MHz): δ 7.26 (d, 1H), 6.77 (d, 1H), 3.37 (s, 2H), 2.80-2.77 (m, 2H), 2.64-2.60 (m, 2H), 2.34 (s, 3H). | CN1CCc2sccc2C1 | null | 32.6 | null |
898,627 | ord_dataset-de6bce51790e4004a27e1a8f2bcc7ded | null | 2009-01-01T00:08:00 | true | [CH3:1][C:2]1[S:3][C:4]2[C:10](=[O:11])[CH:9]([CH:12]=O)[CH2:8][CH2:7][C:5]=2[N:6]=1.[NH:14]1[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1>C1(C)C=CC=CC=1>[CH3:1][C:2]1[S:3][C:4]2[C:10](=[O:11])[C:9](=[CH:12][N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[CH2:8][CH2:7][C:5]=2[N:6]=1 | C1COCCN1 | Cc1nc2c(s1)C(=O)C(C=O)CC2 | 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 | To a solution of 2-methyl-7-oxo-4,5,6,7-tetrahydro-benzothiazole-6-carbaldehyde (2.0 g, 10.2 mmol) in dry toluene (8.1 mL), morpholine (1.0 mL, 1.0 g, 11.3 mmol) was added. The reaction mixture was heated under reflux for 2 h. On cooling a brown precipitate formed. The solvent was removed under vacuum and the brown solid residue was fractionated by flash column chromatography (20% EtOAc:hexane) to leave a yellow solid that was purified further by crystallisation from EtOH to afford the pure title product as yellow crystals (2.4 g, 87%): mp 186-187° C. Anal. RP-HPLC: tR 12.7 min (0-60% MeCN, purity 100%). 1H-NMR (CDCl3): δ 7.50 (s, 1H, CH), 3.80 (t, 4H, J 4.6), 3.55 (t, 4H, J 4.6), 3.00 (m, 4H, CH2—CH2), 2.80 (s, 3H, CH3). 13C-NMR (CDCl3): δ 182.0, 171.6, 162.3, 147.9, 133.2, 103.3, 67.0, 51.4, 26.7, 24.9, 20.2. MS (ESI+): m/z 287.05 (M+Na)+, 265.07 (M+H)+. Anal. (C13H16N2O2S)C, H, N. | Cc1nc2c(s1)C(=O)C(=CN1CCOCC1)CC2 | null | 89 | null |
166,352 | ord_dataset-5c25f386f4664070a72d578feacedf86 | null | 1987-01-01T00:12:00 | true | [C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7]([O-:10])(=[O:9])=[O:8])=[CH:3][CH:2]=1.[F:12][C:13]([F:27])([F:26])[C:14]1[CH:15]=[CH:16][C:17]2[S:21][C:20]([CH3:22])=[N+:19]([CH2:23][CH3:24])[C:18]=2[CH:25]=1.CC(C)=O.[C:32]([O:35][CH2:36][CH3:37])(=O)[CH3:33]>>[C:1]1([CH3:11])[CH:2]=[CH:3][C:4]([S:7]([O-:10])(=[O:8])=[O:9])=[CH:5][CH:6]=1.[F:27][C:13]([F:12])([F:26])[C:14]1[CH:15]=[CH:16][C:17]2[S:21][C:20]([CH:22]=[C:36]3[CH:37]=[C:5]([CH3:4])[C:6]4[C:32](=[CH:33][CH:3]=[CH:2][CH:1]=4)[O:35]3)=[N+:19]([CH2:23][CH3:24])[C:18]=2[CH:25]=1 | CCOC(C)=O | CC[n+]1c(C)sc2ccc(C(F)(F)F)cc21 | null | Cc1ccc(S(=O)(=O)[O-])cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(C)=O | null | null | null | null | null | null | null | null | null | null | 150 | 0.67 | 2.37 g of 5-trifluoromethyl-3-ethyl-2-methylbenzothiazolium p-toluenesulfonate and 1.0 g of 4-methylcoumarin-2-thione were reacted under heat at 150° C. for 20 hours, and then 10 ml of metrhanol, 10 ml of acetone, and 20 ml of ethyl acetate were added to the reaction mixture in the order listed to obtain a uniform solution. After cooling to room temperature, crystals precipitated out therefrom. The crystals formed were separated by filtration and washed with a small amount of acetone, and thereafter the crystlas were placed in a mixed solvent comprising 10 ml of methanol, 10 ml of acetone, and 20 ml of ethyl acetate at room temperature, and stirred for 40 minutes. Then, the crystals were again taken out by filtration and washed with acetone, at last to obtain 1.47 g of the desired p-toluenesulfonate product. Yield: 46%. Appearance: brown crystal. M.P.: 272°-273° C. (decomposition). | CC[n+]1c(C=C2C=C(C)c3ccccc3O2)sc2ccc(C(F)(F)F)cc21 | null | 46 | null |
171,891 | ord_dataset-7860c6f563014da8948ede63b7110bde | null | 1988-01-01T00:05:00 | true | Cl.[NH2:2][C:3]1[S:4][CH:5]=[C:6]([CH2:8][Cl:9])[N:7]=1.N1C=CC=CC=1.[CH3:16][C:17]([CH3:23])([CH3:22])[CH2:18][C:19](Cl)=[O:20]>CN(C)C=O>[CH3:16][C:17]([CH3:23])([CH3:22])[CH2:18][C:19]([NH:2][C:3]1[S:4][CH:5]=[C:6]([CH2:8][Cl:9])[N:7]=1)=[O:20] | CC(C)(C)CC(=O)Cl | Nc1nc(CCl)cs1 | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | c1ccncc1 | CN(C)C=O | null | null | null | null | null | null | null | null | null | 0 | null | To a mixture of 2-amino-4-chloromethylthiazole hydrochloride (5 g), anhydrous pyridine (5 ml) and anhydrous N,N-dimethylformamide (25 ml) was slowly added 3,3-dimethylbutyryl chloride (4.4 g) with stirring at 0° to 3° C. After an hour of stirring, the reaction mixture was poured into ice water. The resulting precipitate was collected, washed with water and dried to give 2-(3,3-dimethylbutyrylamino)-4-chloromethylthiazole (6.62 g). | CC(C)(C)CC(=O)Nc1nc(CCl)cs1 | null | 99.3 | null |
820,366 | ord_dataset-ec58fad8331a42c5a67ad75aac6713b4 | null | 2008-01-01T00:05:00 | true | [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:23][OH:24])[CH:6]=[CH:7][C:8]=1[O:9][CH2:10][C:11]1[N:12]=[C:13]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[S:14][C:15]=1[CH3:16].O[C:26]1[C:30]([CH:31]=[O:32])=[CH:29][N:28]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[N:27]=1.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>O1CCCC1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:6]=[CH:7][C:8]=1[O:9][CH2:10][C:11]1[N:12]=[C:13]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[S:14][C:15]=1[CH3:16])[CH2:23][O:24][C:26]1[C:30]([CH:31]=[O:32])=[CH:29][N:28]([C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[N:27]=1 | COc1cc(CO)ccc1OCc1nc(-c2ccccc2)sc1C | O=Cc1cn(-c2ccccc2)nc1O | null | CCCCP(CCCC)CCCC | O=C(N=NC(=O)N1CCCCC1)N1CCCCC1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | null | 15 | To a mixture of {3-methoxy-4-[(5-methyl-2-phenyl-1,3-thiazol-4-yl)methoxy]phenyl}methanol (0.95 g), 3-hydroxy-1-phenyl-1H-pyrazole-4-carbaldehyde (0.58 g), tributylphosphine (0.85 g) and tetrahydrofuran (100 mL) was added 1,1′-(azodicarbonyl)dipiperidine (1.06 g) at room temperature, and the mixture was stirred for 15 hrs. The precipitated crystals were removed by filtration and the filtrate was concentrated. The residue was subjected to silica gel column chromatography to give 3-({3-methoxy-4-[(5-methyl-2-phenyl-1,3-thiazol-4-yl)methoxy]benzyl}oxy)-1-phenyl-1H-pyrazole-4-carbaldehyde as colorless crystals (0.83 g, yield 58%) from a fraction eluted with ethyl acetate-hexane (2:1, v/v). Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 164-165° C. | COc1cc(COc2nn(-c3ccccc3)cc2C=O)ccc1OCc1nc(-c2ccccc2)sc1C | null | 58.3 | null |
605,235 | ord_dataset-273fda773e864aaf9b71a30a2d9f2162 | null | 2003-01-01T00:08:00 | true | [CH2:1]([NH:5][C:6]([C:8]1[N:9]([CH2:27][CH2:28][CH2:29][C:30]#[N:31])[C:10]2[C:15]([CH:16]=1)=[CH:14][C:13]([O:17][CH2:18][C:19]1[C:24]([Cl:25])=[CH:23][CH:22]=[CH:21][C:20]=1[Cl:26])=[CH:12][CH:11]=2)=[O:7])[CH:2]([CH3:4])[CH3:3].[N:32]([Si](C)(C)C)=[N+:33]=[N-:34].C([Sn](=O)CCCC)CCC>C1(C)C=CC=CC=1>[CH2:1]([NH:5][C:6]([C:8]1[N:9]([CH2:27][CH2:28][CH2:29][C:30]2[NH:34][N:33]=[N:32][N:31]=2)[C:10]2[C:15]([CH:16]=1)=[CH:14][C:13]([O:17][CH2:18][C:19]1[C:24]([Cl:25])=[CH:23][CH:22]=[CH:21][C:20]=1[Cl:26])=[CH:12][CH:11]=2)=[O:7])[CH:2]([CH3:4])[CH3:3] | C[Si](C)(C)N=[N+]=[N-] | CC(C)CNC(=O)c1cc2cc(OCc3c(Cl)cccc3Cl)ccc2n1CCCC#N | null | CCCC[Sn](=O)CCCC | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Cc1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | null | To a solution of 1-(3-cyanopropyl)-5-(2,6-dichlorobenzyloxy)-1H-indole-2-carboxylic acid isobutyl amide (0.076 g, 0.17 mmol) in toluene (10 mL) was added azidotrimethylsilane (0.066 mL, 0.50 mmol) and dibutyltin oxide (0.012 g, 0.050 mmol). The reaction mixture was heated to reflux and stirred under argon at reflux temperature for 40 h. The solution was then cooled and the toluene removed under reduced pressure. Methanol was added and removed under reduced pressure. Ethyl acetate was added and the reaction mixture was washed with water and brine. The organic layer was dried over MgSO4, filtered, and the solvent removed under reduced pressure. Purification by flash chromatography (silica gel, 10% methanol/dichloromethane) yielded a white solid (0.032 g, 38%). MS(ES) m/e 501.2 [M +H]+. | CC(C)CNC(=O)c1cc2cc(OCc3c(Cl)cccc3Cl)ccc2n1CCCc1nnn[nH]1 | null | 37.5 | null |
1,247,454 | ord_dataset-c544c0c663f54dbea4ddb52ddde7934e | null | 2013-01-01T00:01:00 | true | [CH3:1][O:2][C:3]1[C:8]([CH2:9][CH2:10][O:11][C:12]2[CH:20]=[CH:19][CH:18]=[C:17]3[C:13]=2[CH:14]=[C:15]([C:21]([OH:23])=O)[NH:16]3)=[CH:7][CH:6]=[CH:5][N:4]=1.[NH2:24][CH:25]1[CH2:30][CH2:29][C:28]([CH2:32][CH2:33][N:34]2[CH2:39][CH2:38][C@H:37]([OH:40])[C@@H:36]([CH3:41])[CH2:35]2)([OH:31])[CH2:27][CH2:26]1>>[OH:31][C:28]1([CH2:32][CH2:33][N:34]2[CH2:39][CH2:38][C@H:37]([OH:40])[C@@H:36]([CH3:41])[CH2:35]2)[CH2:29][CH2:30][CH:25]([NH:24][C:21]([C:15]2[NH:16][C:17]3[C:13]([CH:14]=2)=[C:12]([O:11][CH2:10][CH2:9][C:8]2[C:3]([O:2][CH3:1])=[N:4][CH:5]=[CH:6][CH:7]=2)[CH:20]=[CH:19][CH:18]=3)=[O:23])[CH2:26][CH2:27]1 | C[C@H]1CN(CCC2(O)CCC(N)CC2)CC[C@@H]1O | COc1ncccc1CCOc1cccc2[nH]c(C(=O)O)cc12 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | This compound is synthesized analogously to example 1 from 4-[2-(2-methoxy-pyridin-3-yl)-ethoxy]-1H-indole-2-carboxylic acid 16m and amine 14. | COc1ncccc1CCOc1cccc2[nH]c(C(=O)NC3CCC(O)(CCN4CC[C@H](O)[C@@H](C)C4)CC3)cc12 | null | null | null |
1,676,149 | ord_dataset-9cc455db05a444779921f786a45b21a6 | null | 2015-01-01T00:12:00 | true | Cl[C:2]1[C:3]2[CH2:17][CH2:16][CH2:15][C:4]=2[N:5]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([Cl:14])[CH:9]=2)[N:7]=1.CN1C(=O)CCC1.[CH3:25][C:26]1[CH:34]=[CH:33][C:29]([CH2:30][Mg]Cl)=[CH:28][CH:27]=1.[Cl-]>C1COCC1>[Cl:14][C:10]1[CH:9]=[C:8]([C:6]2[N:7]=[C:2]([CH2:25][C:26]3[CH:34]=[CH:33][C:29]([CH3:30])=[CH:28][CH:27]=3)[C:3]3[CH2:17][CH2:16][CH2:15][C:4]=3[N:5]=2)[CH:13]=[CH:12][CH:11]=1 | Clc1cccc(-c2nc(Cl)c3c(n2)CCC3)c1 | Cc1ccc(C[Mg]Cl)cc1 | null | [Cl-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN1CCCC1=O | C1CCOC1 | null | null | null | null | null | null | null | null | null | 0 | null | A 25-mL round bottom flask, with stirrer bar, was charged with 4-chloro-2-(3-chlorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine (318 mg, 1.20 mol, 1.0 eq.) and Fe(acac)3 (6.6 mg, 19 mol, 0.05 eq.), NMP (0.4 mL) and THF (4.0 mL). The mixture was cooled to 0° C. under nitrogen. A solution of 4-methylbenzylmagnesium chloride (0.83 mL, 0.5M in THF, 0.41 mmol, 1.1 eq.) was added dropwise over 2 minutes. The resulting mixture was stirred 0° C. for 1.5 hr until the starting chloride was consumed. The reaction was quenched with a 9:1 sat. NH4Cl/conc. NH4OH solution (10 mL) then diluted with ethyl acetate (75 mL). The organic layer was washed with sat. sodium chloride (3×5 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue (175 mg) was purified by chromatography on silica gel using dichloromethane as the eluent, to afford 2-(3-chlorophenyl)-4-(4-methylbenzyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine (65 mg, 52% yield) as a white solid. MW=334.84. 1H NMR (DMSO-d6, 500 MHz) δ 8.35-8.30 (m, 2H), 7.58-7.51 (m, 2H), 7.20 (d, J=8.0 Hz, 2H), 7.11 (d, J=8.0 Hz, 2H), 4.07 (s, 2H), 2.97 (t, J=7.5 Hz, 2H), 2.88 (t, J=7.5 Hz, 2H), 2.25 (s, 3H), 2.06 (quintet, J=7.5 Hz, 2H). | Cc1ccc(Cc2nc(-c3cccc(Cl)c3)nc3c2CCC3)cc1 | null | 47.3 | null |
1,096,106 | ord_dataset-af85e6f81c2d49f08086afd6d9e6959c | null | 2011-01-01T00:10:00 | true | [CH2:1]([O:8][C:9]([NH:11][CH2:12][CH2:13][CH2:14][C@@H:15]([C:29]([NH:31][C@H:32]1[CH2:36][CH2:35][CH2:34][C@H:33]1[C:37]([O:39]C(C)(C)C)=[O:38])=[O:30])[NH:16][C:17]([C:19]1[N:20]([CH3:28])[C:21]2[C:26]([CH:27]=1)=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:18])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.C(OCC)(=O)C>C(Cl)(Cl)Cl>[CH2:1]([O:8][C:9]([NH:11][CH2:12][CH2:13][CH2:14][C@@H:15]([C:29]([NH:31][C@H:32]1[CH2:36][CH2:35][CH2:34][C@H:33]1[C:37]([OH:39])=[O:38])=[O:30])[NH:16][C:17]([C:19]1[N:20]([CH3:28])[C:21]2[C:26]([CH:27]=1)=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:18])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1 | Cn1c(C(=O)N[C@@H](CCCNC(=O)OCc2ccccc2)C(=O)N[C@H]2CCC[C@H]2C(=O)OC(C)(C)C)cc2ccccc21 | null | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClC(Cl)Cl | CCOC(C)=O | null | null | null | null | null | null | null | null | null | 25 | 3 | To a mixture of tert-butyl (1R,2S)-2-({N5-[(benzyloxy)carbonyl]-N2-[(1-methyl-1H-indol-2-yl)carbonyl]-L-ornithyl}amino)cyclopentanecarboxylate (0.40 g) and chloroform (10 ml) was added a 4 M hydrogen chloride/ethyl acetate solution (20 ml) under ice-cooling, followed by stirring at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure, and to the residue were added ethyl acetate and water. The aqueous layer was separated, and the organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The organic layer was concentrated under reduced pressure, and diethyl ether was added to the residue for solidification, followed by washing with diethyl ether and a 50% aqueous methanol solution. Further, it was purified by silica gel column chromatography (0→2% MeOH/chloroform), and the obtained solid was washed with a 50% aqueous methanol solution to obtain (1R,2S)-2-({N5-[(benzyloxy)carbonyl]-N2-[(1-methyl-1H-indol-2-yl)carbonyl]-L-ornithyl}amino)cyclopentanecarboxylic acid (0.25 g). | Cn1c(C(=O)N[C@@H](CCCNC(=O)OCc2ccccc2)C(=O)N[C@H]2CCC[C@H]2C(=O)O)cc2ccccc21 | null | 69.1 | null |
589,827 | ord_dataset-7a74d48eeefd45aba53e7258f3ae067a | null | 2003-01-01T00:04:00 | true | C(OC(=O)[NH:7][C:8]1[CH:13]=[C:12]([N:14]([CH3:16])[CH3:15])[C:11]([Cl:17])=[CH:10][C:9]=1[NH:18][C:19](=[O:38])[CH2:20][C:21]([C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([N:29]2[C:33]([CH2:34][N:35]([CH3:37])[CH3:36])=[CH:32][N:31]=[N:30]2)[CH:24]=1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:17][C:11]1[C:12]([N:14]([CH3:16])[CH3:15])=[CH:13][C:8]2[N:7]=[C:21]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([N:29]4[C:33]([CH2:34][N:35]([CH3:37])[CH3:36])=[CH:32][N:31]=[N:30]4)[CH:24]=3)[CH2:20][C:19](=[O:38])[NH:18][C:9]=2[CH:10]=1 | CN(C)Cc1cnnn1-c1cccc(C(=O)CC(=O)Nc2cc(Cl)c(N(C)C)cc2NC(=O)OC(C)(C)C)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O=C(O)C(F)(F)F | ClCCl | null | null | null | null | null | null | null | null | null | null | null | The title compound was prepared from (4-chloro-5-dimethylamino-2-{3-[3-(5-dimethylaminomethyl-[1,2,3]triazol-1-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamic acid tert.-butyl ester (Example M19) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a beige solid (34 mg). | CN(C)Cc1cnnn1-c1cccc(C2=Nc3cc(N(C)C)c(Cl)cc3NC(=O)C2)c1 | null | null | null |
1,532,321 | ord_dataset-8d5c200bca27407ab9febe7598e16458 | null | 2015-01-01T00:01:00 | true | [NH2:1][CH:2]([C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][CH:7]=1)[C:3]([OH:5])=[O:4].Cl[C:14](Cl)([O:16]C(=O)OC(Cl)(Cl)Cl)Cl>C1COCC1>[F:12][C:9]1[CH:10]=[CH:11][C:6]([CH:2]2[C:3](=[O:5])[O:4][C:14](=[O:16])[NH:1]2)=[CH:7][CH:8]=1 | NC(C(=O)O)c1ccc(F)cc1 | O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | -20 | 3 | To a solution of 2-amino-2-(4-fluorophenyl)acetic acid (5 g, 29.5 mmol) in THF (50 mL) at 50° C. was added triphosgene (8.77 g, 29.5 mmol), then heating was continued for 3 h. The reaction mixture was then filtered and evaporated to a volume of about 10 mL, followed by addition of 150 mL of hexanes. The mixture was heated slightly, and then cooled to −20° C. for 1 h. The crude slurry was filtered to give 4-(4-fluorophenyl)oxazolidine-2,5-dione (5.03 g, 87%) which was used without further purification. | O=C1NC(c2ccc(F)cc2)C(=O)O1 | null | 87.4 | null |
1,138,682 | ord_dataset-68715347640045adb1b09e6a04722b0e | null | 2012-01-01T00:03:00 | true | [OH-].[Na+].Br[CH2:4][C@H:5]([C:7]1[CH:12]=[CH:11][C:10]([Br:13])=[CH:9][CH:8]=1)[OH:6]>C(OCC)C>[Br:13][C:10]1[CH:11]=[CH:12][C:7]([C@H:5]2[CH2:4][O:6]2)=[CH:8][CH:9]=1 | O[C@H](CBr)c1ccc(Br)cc1 | null | null | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOCC | null | null | null | null | null | null | null | null | null | null | 25 | 5 | Aqueous sodium hydroxide (1M, 400 ml) was added to 2-bromo-(1S)-1-(4-bromophenyl)ethanol (77.0 g) in diethyl ether (400 ml) and stirred at room temperature for 5 hours. The organic layer was separated and aqueous layer was extracted with ether. The combined organic layer was washed with brine and dried over anhydrous sodium sulfate. Removal of the solvent yielded (2S)-2-(4-bromophenyl) oxirane (55.0 g) as a pale brown oil. | Brc1ccc([C@H]2CO2)cc1 | null | 100.5 | null |
496,423 | ord_dataset-9df8b3ec9c8742b3802e0efaac6f6ef3 | null | 2001-01-01T00:03:00 | true | C[O:2][C:3](=O)[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][S:15][CH2:16][CH2:17][S:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][C:30](O)=[O:31].[H-].[Al+3].[Li+].[H-].[H-].[H-].[H][H]>C1COCC1>[CH2:17]([S:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][OH:31])[CH2:16][S:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][OH:2] | [H][H] | COC(=O)CCCCCCCCCCCSCCSCCCCCCCCCCCC(=O)O | null | [Al+3] | [H-] | [Li+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | 30 | 4 | Ethylenedithio-bislauryl alcohol was prepared as the final intermediate as ethylenedithio-bislauric acid methyl ester (8 g) was dissolved in dry THF at 0° C. (ice bath). Lithium aluminum hydride (1.16 g) was added to the flask slowly. Hydrogen was generated, and the reaction temperature was gradually raised to 30° C. After stirring for 4 hours, the reaction was quenched by pouring the solution thus formed into ice water. The aqueous solution was neutralized by adding concentrated HCl, and the crude product was then extracted with ethyl acetate three times. After evaporating the solvents, the compound (7.0 gm) was dried under vacuum and analyzed by NMR. NMR data agrees with the expected structure of the final product as set forth in the reaction summary below. | OCCCCCCCCCCCCSCCSCCCCCCCCCCCCO | null | null | null |
592,948 | ord_dataset-278fb6af8a994ac69e4d95e6e6eff756 | null | 2003-01-01T00:05:00 | true | [C:1](Cl)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:10]([NH2:18])[CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>C(Cl)Cl>[CH2:10]([NH:18][C:1](=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1 | NCCc1ccccc1 | O=C(Cl)c1ccccc1 | 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 | 3 | To a solution of benzoyl chloride (0.123 moles) (Aldrich) in 600 mL of CH2Cl2 was added 2.0 eq. of phenethylamine (Aldrich) dropwise. The reaction mixture was stirred at room temperature for 3 hours and then poured into a separatory and extracted with CH2Cl2. The organic extracts were washed with water and 1N HCl, and then dried over Na2SO4, filtered and concentrated to give N-phenethyl benzamide. | O=C(NCCc1ccccc1)c1ccccc1 | null | null | null |
1,501,423 | ord_dataset-366bdd9ee72d474cbe6f3f9e54dd96d2 | null | 2014-01-01T00:10:00 | true | [C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([C:17]3[C:18]([CH2:30][CH3:31])=[CH:19][C:20]([CH:27]4[CH2:29][CH2:28]4)=[C:21]([CH:26]=3)[C:22](OC)=[O:23])=[O:16])[CH2:11][CH2:10]2)=[CH:5][CH:4]=1)#[N:2].[NH2:32][NH2:33]>C(O)C>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:10][CH2:11][N:12]([C:15]([C:17]3[C:18]([CH2:30][CH3:31])=[CH:19][C:20]([CH:27]4[CH2:29][CH2:28]4)=[C:21]([CH:26]=3)[C:22]([NH:32][NH2:33])=[O:23])=[O:16])[CH2:13][CH2:14]2)=[CH:5][CH:4]=1)#[N:2] | NN | CCc1cc(C2CC2)c(C(=O)OC)cc1C(=O)N1CCC(c2ccc(C#N)cc2)CC1 | 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 | 100 | 15 | To a round-bottom flask was added a solution of methyl 5-(4-(4-cyanophenyl)piperidine-1-carbonyl)-2-cyclopropyl-4-ethylbenzoate (compound 228.1, 830 mg, 1.99 mmol, 1.00 equiv) in ethanol (15 mL). Hydrazine (5 mL, 100 equiv) was added to the reaction. The resulting solution was stirred for 15 h at 100° C., then concentrated in vacuo. The residue was extracted with 100 mL of dichloromethane and the combined organic layers were washed with 1×30 mL of brine, dried over anhydrous sodium sulfate and concentrated in vacuo. This resulted in 0.800 g (96%) of 5-(4-(4-cyanophenyl)piperidine-1-carbonyl)-2-cyclopropyl-4-ethylbenzohydrazide as a white solid. | CCc1cc(C2CC2)c(C(=O)NN)cc1C(=O)N1CCC(c2ccc(C#N)cc2)CC1 | null | null | null |
768,886 | ord_dataset-8214eb8444a44dc2900ccb42dbeff15e | null | 2007-01-01T00:05:00 | true | Br[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]([NH2:13])=[O:12])[CH:9]=2)[N:4]([CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][O:15]2)[N:3]=1.[S:20]1[C:24](B(O)O)=[CH:23][C:22]2[CH:28]=[CH:29][CH:30]=[CH:31][C:21]1=2.ClCCl.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>COCCOC>[S:20]1[C:24]([C:2]2[C:10]3[C:5](=[CH:6][CH:7]=[C:8]([C:11]([NH2:13])=[O:12])[CH:9]=3)[N:4]([CH:14]3[CH2:19][CH2:18][CH2:17][CH2:16][O:15]3)[N:3]=2)=[CH:23][C:22]2[CH:28]=[CH:29][CH:30]=[CH:31][C:21]1=2 | OB(O)c1cc2ccccc2s1 | NC(=O)c1ccc2c(c1)c(Br)nn2C1CCCCO1 | null | O=P([O-])([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | COCCOC | null | null | null | null | null | null | null | null | null | null | null | A mixture of 3-bromo-1-perhydro-2H-pyran-2-yl-1H-indazole-5-carboxamide (425 mg, 1.31 mmol), benzo[b]thiophene-2-boronic acid (348 mg, 1.95 mmol, 1.49 equiv.), [1,1′-bis(diphenylphosphino)-ferrocene} dichloropalladium (II) complex with dichloromethane (107 mg, 0.131 mmol, 0.10 equiv.), potassium phosphate (K3PO4, 1.38 g, 6.50 mmol, 4.96 equiv.) and 6.5 mL of DME were refluxed for 18 h and concentrated. Purification by silica gel chromatography using 0–5% MeOH in EtOAc as eluent afforded the title compound (126 mg, 26% yield): ES-MS (m/z) 378 [M+1]+. | NC(=O)c1ccc2c(c1)c(-c1cc3ccccc3s1)nn2C1CCCCO1 | null | 25.5 | null |
1,153,990 | ord_dataset-b195433d5c354ddfb6cde0d53c41910f | null | 2012-01-01T00:04:00 | true | [C:1]([O:5][C:6](=[O:33])[N:7]([C@@H:21]([C:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:26]=[CH:25][CH:24]=1)[CH3:22])[CH2:8][CH:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH:10]1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)([CH3:4])([CH3:3])[CH3:2].Br[C:35]1[S:36][CH:37]=[C:38]([C:40]([O:42][CH3:43])=[O:41])[N:39]=1.C(=O)([O-])[O-].[K+].[K+].CS(C)=O>O>[C:1]([O:5][C:6]([N:7]([CH2:8][CH:9]1[CH2:14][CH2:13][N:12]([C:35]2[S:36][CH:37]=[C:38]([C:40]([O:42][CH3:43])=[O:41])[N:39]=2)[CH2:11][CH:10]1[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)[C@@H:21]([C:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:26]=[CH:25][CH:24]=1)[CH3:22])=[O:33])([CH3:2])([CH3:3])[CH3:4] | C[C@H](c1cccc2ccccc12)N(CC1CCNCC1c1ccccc1)C(=O)OC(C)(C)C | COC(=O)c1csc(Br)n1 | null | O=C([O-])[O-] | [K+] | 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 | 25 | 8 | To a mixture of 136 mg of the crude tert-butyl[(1R)-1-(1-naphthyl)ethyl][(3-phenylpiperidin-4-yl)methyl]carbamate, 64 mg of methyl 2-bromo-1,3-thiazole-4-carboxylate, and 38 mg of potassium carbonate was added 1.5 mL of DMSO at room temperature, and the mixed solution was stirred at room temperature overnight. To the reaction mixture was added water, followed by extraction with ethyl acetate, and the organic layer was then washed with water and saturated brine in this order, and then dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain 113 mg of methyl 2-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-phenylpiperidin-1-yl]-1,3-thiazole-4-carboxylate as a colorless foamy substance. ESI+: 586 | COC(=O)c1csc(N2CCC(CN(C(=O)OC(C)(C)C)[C@H](C)c3cccc4ccccc34)C(c3ccccc3)C2)n1 | null | 66.9 | null |
1,064,886 | ord_dataset-ffbef48837674f39816de887b5dc8bae | null | 2011-01-01T00:06:00 | true | [C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]([C:30](Cl)=[O:31])[C@H:13]([C:23]3[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=3)[C@H:14]([C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[N:15]=2)=[C:7]([O:33][CH2:34][CH3:35])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].Cl.[N:37]1([CH2:43][CH2:44][NH:45][C:46](=[O:48])[CH3:47])[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1>>[ClH:22].[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]([C:30]([N:40]3[CH2:41][CH2:42][N:37]([CH2:43][CH2:44][NH:45][C:46](=[O:48])[CH3:47])[CH2:38][CH2:39]3)=[O:31])[C@H:13]([C:23]3[CH:24]=[CH:25][C:26]([Cl:29])=[CH:27][CH:28]=3)[C@H:14]([C:16]3[CH:17]=[CH:18][C:19]([Cl:22])=[CH:20][CH:21]=3)[N:15]=2)=[C:7]([O:33][CH2:34][CH3:35])[CH:6]=1)([CH3:4])([CH3:2])[CH3:3] | CCOc1cc(C(C)(C)C)ccc1C1=N[C@@H](c2ccc(Cl)cc2)[C@@H](c2ccc(Cl)cc2)N1C(=O)Cl | CC(=O)NCCN1CCNCC1 | 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 | N-(2-{4-[(4S,5R)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-ethyl)-acetamide hydrochloride was prepared from (4S,5R)-2-(4-tert-butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dihydro-imidazole-1-carbonyl chloride (example 11) and N-(2-piperazin-1-yl-ethyl)-acetamide hydrochloride (example 23) in an analogous manner as described in example 25. LR-MS: 664.5 [(M+H)+] | CCOc1cc(C(C)(C)C)ccc1C1=N[C@@H](c2ccc(Cl)cc2)[C@@H](c2ccc(Cl)cc2)N1C(=O)N1CCN(CCNC(C)=O)CC1 | null | null | null |
1,460,355 | ord_dataset-a86112d52cd54525a5e36d41f18aced2 | null | 2014-01-01T00:07:00 | true | [CH2:1]([O:8][CH2:9][C@@H:10]([C:12]1[NH:16][C:15]2[CH:17]=[CH:18][C:19]([O:21][C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)=[CH:20][C:14]=2[N:13]=1)[NH2:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[NH:30]1[CH:34]=[C:33]([CH2:35][C:36](O)=[O:37])[N:32]=[CH:31]1>>[CH2:1]([O:8][CH2:9][C@H:10]([NH:11][C:36](=[O:37])[CH2:35][C:33]1[N:32]=[CH:31][NH:30][CH:34]=1)[C:12]1[NH:16][C:15]2[CH:17]=[CH:18][C:19]([O:21][C:22]3[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=3)=[CH:20][C:14]=2[N:13]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1 | N[C@@H](COCc1ccccc1)c1nc2cc(Oc3ccc(F)cc3)ccc2[nH]1 | O=C(O)Cc1c[nH]cn1 | 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 | Proceeding as in Example 1, but substituting (R)-2-(benzyloxy)-1-(5-(4-fluorophenoxy)-1H-benzo[d]imidazol-2-yl)ethanamine and 4-imidazoleacetic acid hydrochloride gave Compound 59, (R)—N-(2-(benzyloxy)-1-(5-(4-fluorophenoxy)-1H-benzo[d]imidazol-2-yl)ethyl)-2-(1H-imidazol-4-yl)acetamide (75 mg, 39%). 1H NMR (400 MHz, DMSO-d6) δ 8.75 (d, J=8.0 Hz, 1H), 7.77 (s, 1H), 7.56 (d, J=9.2 Hz, 1H), 7.33-7.25 (m, 5H), 7.20-7.16 (m, 3H), 7.00-6.96 (m, 3H), 6.89 (dd, J=8.8, 2.0 Hz, 1H), 5.35-5.30 (m, 1H), 4.52 (s, 2H), 3.95-3.84 (m, 2H), 3.56-3.46 (m, 2H); ESI MS: m/z 486.2 (M+1). | O=C(Cc1c[nH]cn1)N[C@@H](COCc1ccccc1)c1nc2cc(Oc3ccc(F)cc3)ccc2[nH]1 | null | 39 | null |
181,213 | ord_dataset-ed5a3d1f8dc744759e7fa1c320a44e59 | null | 1988-01-01T00:11:00 | true | [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1/[C:9](/[C:16]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=1)=[CH:10]/[CH:11]=[CH:12]/[C:13]([OH:15])=[O:14].[N+:24]([C:27]1[CH:32]=[CH:31][C:30](O)=[CH:29][CH:28]=1)([O-:26])=[O:25].C1(N=C=NC2CCCCC2)CCCCC1>ClCCl>[N+:24]([C:27]1[CH:32]=[CH:31][C:30]([O:14][C:13](=[O:15])/[CH:12]=[CH:11]/[CH:10]=[C:9](/[C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[O:2][CH3:1])\[C:16]2[CH:17]=[CH:18][C:19]([O:22][CH3:23])=[CH:20][CH:21]=2)=[CH:29][CH:28]=1)([O-:26])=[O:25] | O=[N+]([O-])c1ccc(O)cc1 | COc1ccc(/C(=C\C=C\C(=O)O)c2ccccc2OC)cc1 | null | C(=NC1CCCCC1)=NC1CCCCC1 | 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 | As in Example 115, (E,E)-5-(2-methoxyphenyl)-5-(4-methoxyphenyl)-2,4-pentadienoic acid (3.4 g) and 4-nitrophenol (1.8 g) in 25 mL of dichloromethane was treated with 1,3-dicyclohexylcarbodiimide (2.27 g). The mixture was stirred at room temperature for 2 hours. After the usual work up, the ester was crystallized from 2-propanol to yield 3.0 g of (E,E)-5-(2-methoxyphenyl)-5-(4-methoxyphenyl)-2,4-pentadienoic acid 4-nitrophenyl ester, mp 149°-150° C. | COc1ccc(/C(=C\C=C\C(=O)Oc2ccc([N+](=O)[O-])cc2)c2ccccc2OC)cc1 | null | 63.5 | null |
474,044 | ord_dataset-cd531114850e4f239b2a3661044ae672 | null | 2000-01-01T00:08:00 | true | Br[CH2:2][C:3]([O:5][CH3:6])=[O:4].[Br:7][C:8]1[CH:13]=[C:12]([C:14]2[C:23]3[C:24]4[CH:30]=[CH:29][CH:28]=[CH:27][C:25]=4[O:26][C:22]=3[C:21]([Br:31])=[C:20]3[C:15]=2[CH:16]=[CH:17][CH:18]=[CH:19]3)[CH:11]=[C:10]([Br:32])[C:9]=1[OH:33].C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[CH3:6][O:5][C:3](=[O:4])[CH2:2][O:33][C:9]1[C:8]([Br:7])=[CH:13][C:12]([C:14]2[C:23]3[C:24]4[CH:30]=[CH:29][CH:28]=[CH:27][C:25]=4[O:26][C:22]=3[C:21]([Br:31])=[C:20]3[C:15]=2[CH:16]=[CH:17][CH:18]=[CH:19]3)=[CH:11][C:10]=1[Br:32] | Oc1c(Br)cc(-c2c3ccccc3c(Br)c3oc4ccccc4c23)cc1Br | COC(=O)CBr | null | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | 21 | Methyl bromoacetate (0.554 mL, 5.8 mmol) was added to a stirred, room temperature suspension of 2, 6-dibromo-4-(6-bromo-benzo[b]naphtho[2,3-d]furan-11yl)-phenol (1.6 g, 2.92 mmol), potassium carbonate (0.81 g, 5.8 mmol) and dimethylformamide (7 mL). After 21 h, the reaction mixture was added to water and filtered. The solid was taken up in THF and silica gel was added. The solvent was removed. The adsorbate was flash chromatographed (9:1 petroleum ether:ethyl acetate as eluent) to provide the title compound as a white solid (0.987 g, 55%): mp 188-189° C.: NMR (DMSO-d6); δ8.37 (d, J=8 Hz, 1 H), 7.91 (s, 2 H), 7.84 (d, J=8 Hz, 1 H), 7.80 (ddd, J=8, 7, 1 Hz, 1 H), 7.70 (d, J=8 Hz, 1 H), 7.64-7.58 (m, 2 H), 7.31 (t, J=8 Hz, 1 H), 6.92 (d, J=8, 1 H), 4.88 (s, 2 H), 3.80 (s, 3 H); MS (EI): [M+], 3 bromine isotope pattern, 616 (30%), 618 (100%) 620 (100%) 622 (30%); Anal. Calc. for C25H15Br3O4: C, 48.50, H, 2.44, N, 0.00. Found: C, 48.53, H, 2.29, N, 0.00. | COC(=O)COc1c(Br)cc(-c2c3ccccc3c(Br)c3oc4ccccc4c23)cc1Br | null | 54.6 | null |
256,208 | ord_dataset-30ad5cf6083a45a387b45bebad1a4d65 | null | 1992-01-01T00:10:00 | true | [C:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1[CH:16]=[CH:15][C:14]([CH2:17][N:18]2[C:22]([CH2:23][OH:24])=[C:21]([Cl:25])[N:20]=[C:19]2[CH2:26][CH2:27][CH2:28][CH3:29])=[CH:13][CH:12]=1)([O:3]C)=[O:2].C(O)(=[O:32])C>O.[O-2].[O-2].[O-2].[Cr+6]>[C:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1[CH:12]=[CH:13][C:14]([CH2:17][N:18]2[C:22]([C:23]([OH:24])=[O:32])=[C:21]([Cl:25])[N:20]=[C:19]2[CH2:26][CH2:27][CH2:28][CH3:29])=[CH:15][CH:16]=1)([OH:3])=[O:2] | CC(=O)O | CCCCc1nc(Cl)c(CO)n1Cc1ccc(-c2ccccc2C(=O)OC)cc1 | null | [Cr+6] | [O-2] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | null | null | null | null | null | null | null | null | null | null | null | 0.25 | To a solution of 1.03 g of 1-[(2'-carbomethoxybiphenyl-4-yl)methyl]-2-butyl-4-chloro-5-hydroxymethylimidazole in 10 mL of anhydrous acetic acid at 25° was added a solution of 0.62 g of chromium trioxide in 10 mL of water. The mixture was stirred at 25° for 15 minutes and then poured into water. The precipitated solids were recovered by filtration and then dissolved in 50 mL of 1.0N aqueous sodium hydroxide solution. The alkaline solution was allowed to stand at 25° overnight and then was acidified to pH 3 with 10% aqueous hydrochloric acid. The precipitated solid was recovered by filtration and recrystallized from ethyl acetate to afford 0.10 g of 1-[(2'-carboxybiphenyl-4-yl)methyl]-2-butyl-4-chloroimidazole-5-carboxylic acid (m.p. 186°-187° (decomp.)). NMR (DMSO-d6) δ 12.97 (br s, 2H); 7.68 (d, 1H); 7.53 (t, 1H); 7.41 (t, 1H); 7.34 (d, 1H); 7.28 (d, 2H); 7.02 (d, 2H); 5.61 (s, 2H); 2.60 (t, 2H); 1.53 (quint., 2H); 1.27 (sext., 2H); 0.81 (t, 3H). | CCCCc1nc(Cl)c(C(=O)O)n1Cc1ccc(-c2ccccc2C(=O)O)cc1 | null | null | null |
1,207,037 | ord_dataset-fb72428f30234761b4216139dc228d0c | null | 2012-01-01T00:09:00 | true | [F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH2:8][N:7]([CH2:12][CH2:13][NH2:14])[CH:6]([CH2:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=1)[CH2:5]2.[CH2:23]([C:25]1[CH:30]=[C:29]([CH2:31]OS(C)(=O)=O)[CH:28]=[CH:27][N:26]=1)[CH3:24].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[CH2:23]([C:25]1[CH:30]=[C:29]([CH2:31][NH:14][CH2:13][CH2:12][N:7]2[CH:6]([CH2:15][C:16]3[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=3)[CH2:5][C:4]3[C:9](=[CH:10][CH:11]=[C:2]([F:1])[CH:3]=3)[CH2:8]2)[CH:28]=[CH:27][N:26]=1)[CH3:24] | NCCN1Cc2ccc(F)cc2CC1Cc1ccc(F)cc1 | CCc1cc(COS(C)(=O)=O)ccn1 | 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 | 60 | 2 | 67 mg of 2-[6-fluoro-3-(4-fluorobenzyl)-3,4-dihydroisoquinolin-2(1H)-yl]ethanamine obtained in Example 180-b), 47 mg of 2-ethyl-4-[(methyl sulfonyl oxy)methyl]pyridine, and 30 mg of potassium carbonate were added to acetonitrile (2 ml), followed by stirring at 60° C. for 2 hours. After concentration, it was purified by PLC (chloroform:methanol=10:1) to obtain 26 mg (yield 28%) of a title compound as a yellow oily substance. | CCc1cc(CNCCN2Cc3ccc(F)cc3CC2Cc2ccc(F)cc2)ccn1 | null | 28.3 | null |
465,489 | ord_dataset-6c36eb0f817d4144988b8963c5d58879 | null | 2000-01-01T00:05:00 | true | [H-].[Na+].[CH:3]1([CH:6]([C:8]2[O:9][C:10]3[C:16]([O:17][CH3:18])=[CH:15][CH:14]=[CH:13][C:11]=3[CH:12]=2)[OH:7])[CH2:5][CH2:4]1.I[CH3:20]>O1CCCC1>[CH:3]1([CH:6]([O:7][CH3:20])[C:8]2[O:9][C:10]3[C:16]([O:17][CH3:18])=[CH:15][CH:14]=[CH:13][C:11]=3[CH:12]=2)[CH2:4][CH2:5]1 | CI | COc1cccc2cc(C(O)C3CC3)oc12 | 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 | null | 0.08 | To a stirred suspension of sodium hydride (60% dispersion in mineral oil, 0.52 g) in tetrahydrofuran (60 ml) under an atmosphere of nitrogen was added slowly a solution of cyclopropyl-(7-methoxybenzofuran-2-yl)-methanol (1.88 g) in tetrahydrofuran (15 ml). After stirring for 5 minutes, iodomethane (1.6 ml) was added and the mixture concentrated in vacuo. The residue was partitioned between ethyl acetate (100 ml) and water (100 ml), the organic layer washed with water (100 ml), separated, dried over magnesium sulfate, filtered and concentrated in vacuo. Purification by flash chromatography on silica eluting with dichloromethane afforded the title compound as a yellow gum (1.62 g). | COc1cccc2cc(C(OC)C3CC3)oc12 | null | null | null |
834,098 | ord_dataset-ec576c604a9d47258c87c732a043ec71 | null | 2008-01-01T00:08:00 | true | [Br:1][C:2]1[CH:3]=[C:4]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([N+:17]([O-])=O)=[CH:13][CH:12]=3)[NH:8][C:5]2=[N:6][CH:7]=1.CO>>[Br:1][C:2]1[CH:3]=[C:4]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([NH2:17])=[CH:13][CH:12]=3)[NH:8][C:5]2=[N:6][CH:7]=1 | O=[N+]([O-])c1ccc(-c2nc3cc(Br)cnc3[nH]2)cc1 | null | 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 | 25 | 0.5 | To a stirred solution of 6-bromo-2-(4-nitrophenyl)-3H-imidazo[4,5-b]pyridine (1.6 g, 5 mmol) in methanol (45 ml) ammonium sulfide (8.5 ml, 25 mmol, 20% solution in water) was added slowly. The mixture was stirred at room temperature for 30 minutes and then heated and refluxed for 5 h. The reaction mixture was concentrated and cooled to 0° C. The precipitate was filtered off, washed with cold methanol and dried to give the title compound. | Nc1ccc(-c2nc3cc(Br)cnc3[nH]2)cc1 | null | null | null |
549,710 | ord_dataset-e967d076b4894c2c854795f019ed3c39 | null | 2002-01-01T00:06:00 | true | [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7]O)[CH:2]=1.[BrH:9]>CCOC(C)=O>[BrH:9].[Br:9][CH2:7][C:3]1[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=1 | OCc1cccnc1 | null | null | Br | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOC(C)=O | null | null | null | null | null | null | null | null | null | null | null | null | To 3-pyridylcarbinol (2 g, 18.3 mmol) was added 47-49% hydrobromic acid (2 mL, 13.7 mmol). The solution was refluxed for 3 hours. The solution was diluted with EtOAc and extracted thrice with EtOAc. The organic layer was dried over MgSO4, filtered and concentrated under reduced pressure to give a solid. The solid was recrystallized in ethanol to afford the title compound as a white solid (2.13 g, 45.8%). ES (+) MS m/e=173 (M+H). | BrCc1cccnc1 | null | 122.9 | null |
330,334 | ord_dataset-2c460e2ef9934444aaf26fec1f75741f | null | 1996-01-01T00:05:00 | true | [Cl:1][C:2]1[C:3]([CH2:12][C:13]([CH3:15])=[CH2:14])=[C:4]([OH:11])[C:5]([N+:8]([O-:10])=[O:9])=[CH:6][CH:7]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C(C)=CC=CC=1>[Cl:1][C:2]1[C:3]2[CH2:12][C:13]([CH3:15])([CH3:14])[O:11][C:4]=2[C:5]([N+:8]([O-:10])=[O:9])=[CH:6][CH:7]=1 | C=C(C)Cc1c(Cl)ccc([N+](=O)[O-])c1O | null | null | Cc1ccc(S(=O)(=O)O)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Cc1ccccc1C | null | null | null | null | null | null | null | null | null | null | null | null | A mixture of 20.0 g (0.088 mole) of 3-chloro-2-(2-methyl-2-propen-1-yl)-6-nitrophenol and 0.35 g (0.002 mole) of p-toluenesulfonic acid in 100 mL of xylene was heated at reflux for approximately 16 hours. The solvent was evaporated under reduced pressure, leaving a residue which was passed through a column of silica gel, eluting with methylene chloride. The product-containing fractions were combined, washed with an aqueous solution of sodium hydroxide, dried over anhydrous magnesium sulfate, and the solvent evaporated under reduced pressure, yielding 16.85 g of 4-chloro-2,3-dihydro-2,2-dimethyl-7-nitrobenzofuran as an oil. | CC1(C)Cc2c(Cl)ccc([N+](=O)[O-])c2O1 | null | 84.1 | null |
1,227,093 | ord_dataset-cde802cdb7434a5f82a22981ccaefc4e | null | 2012-01-01T00:11:00 | true | C([O:3][C:4]([C:6]1[S:10][C:9]([C:11]2[CH:15]=[C:14]([CH3:16])[N:13]([CH2:17][CH2:18][C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)[N:12]=2)=[N:8][C:7]=1[CH3:26])=[O:5])C.[OH-].[Na+]>O1CCCC1.O>[F:25][C:22]1[CH:23]=[CH:24][C:19]([CH2:18][CH2:17][N:13]2[C:14]([CH3:16])=[CH:15][C:11]([C:9]3[S:10][C:6]([C:4]([OH:5])=[O:3])=[C:7]([CH3:26])[N:8]=3)=[N:12]2)=[CH:20][CH:21]=1 | CCOC(=O)c1sc(-c2cc(C)n(CCc3ccc(F)cc3)n2)nc1C | null | null | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | null | A mixture of 2-{1-[2-(4-fluoro-phenyl)-ethyl]-5-methyl-1H-pyrazol-3-yl}-4-methyl-thiazole-5-carboxylic acid ethyl ester (0.32 g, 0.86 mmol), NaOH (0.17 g, 4.29 mmol) in tetrahydrofuran (5 mL) and water (5 mL) was heated to reflux for 16 hr. The solvent was removed in vacuo and the residue was neutralized with 5% HCl to pH 5-6. The resulting solid was filtered and dried to provide 2-{1-[2-(4-fluoro-phenyl)-ethyl]-5-methyl-1H-pyrazol-3-yl}-4-methyl-thiazole-5-carboxylic acid as a white solid (0.21 g, 70% yield). This material was used without further purification. | Cc1nc(-c2cc(C)n(CCc3ccc(F)cc3)n2)sc1C(=O)O | null | 70.7 | null |
785,964 | ord_dataset-4ad5db8537994579bef51f16dd8bf0bd | null | 2007-01-01T00:08:00 | true | Br[C:2]1[N:3]=[C:4]([NH:11][CH2:12][C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)[C:5]2[N:6]([CH:8]=[CH:9][N:10]=2)[CH:7]=1.[NH2:19][C:20]1[CH:21]=[C:22](B(O)O)[CH:23]=[CH:24][CH:25]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[NH2:19][C:20]1[CH:25]=[C:24]([C:2]2[N:3]=[C:4]([NH:11][CH2:12][C:13]3[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=3)[C:5]3[N:6]([CH:8]=[CH:9][N:10]=3)[CH:7]=2)[CH:23]=[CH:22][CH:21]=1 | Nc1cccc(B(O)O)c1 | Brc1cn2ccnc2c(NCc2ccncc2)n1 | null | c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1 | O=P([O-])([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 | 25 | null | A mixture of (6-Bromo-imidazo[1,2-a]pyrazin-8-yl)-pyridin-4-ylmethyl-amine 4 (1.0 equiv.), 3-aminophenyl boronic acid (1.1 equiv.), Pd (PPh3)4 (0.10 equiv.), and K3PO4 (2.20 equiv.) in 4:1 1,4-dioxane:water is heated to 90° C. for 24 hr. The mixture is cooled to RT and partitioned between EtOAc and sat. NaHCO3. The aqueous phase is extracted with EtOAc and combined extracts are dried over Na2SO4. The solvent is removed under reduced pressure and the resulting residue is purified by flash chromatography (EtOAc) to yield [6-(3-Amino-phenyl)-imidazo[1,2-a]pyrazin-8-yl]-pyridin-4-ylmethyl-amine 5. | Nc1cccc(-c2cn3ccnc3c(NCc3ccncc3)n2)c1 | null | null | null |
834,094 | ord_dataset-ec576c604a9d47258c87c732a043ec71 | null | 2008-01-01T00:08:00 | true | [Br:1][C:2]1[CH:3]=[C:4]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH:19]4[CH2:21][O:20]4)=[CH:13][CH:12]=3)[NH:8][C:5]2=[N:6][CH:7]=1.[NH:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1>>[Br:1][C:2]1[CH:3]=[C:4]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH:19]([OH:20])[CH2:21][N:22]4[CH2:27][CH2:26][O:25][CH2:24][CH2:23]4)=[CH:13][CH:12]=3)[NH:8][C:5]2=[N:6][CH:7]=1 | Brc1cnc2[nH]c(-c3ccc(OCC4CO4)cc3)nc2c1 | C1COCCN1 | null | null | null | null | null | null | null | 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 6-bromo-2-[4-(oxiran-2-ylmethoxy)phenyl]-3H-imidazo[4,5-b]pyridine and morpholine. | OC(COc1ccc(-c2nc3cc(Br)cnc3[nH]2)cc1)CN1CCOCC1 | null | null | null |
1,013,674 | ord_dataset-f024e9664ab64906a71a2ff6004cb3d0 | null | 2010-01-01T00:12:00 | true | [CH3:1][NH:2][C:3]1[C:8]([CH:9]=[O:10])=[CH:7][N:6]=[C:5]2[NH:11][CH:12]=[CH:13][C:4]=12.C([O-])([O-])=O.[Na+].[Na+].[CH2:20](Br)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>CN(C=O)C>[CH2:20]([N:6]1[CH:7]=[C:8]([CH:9]=[O:10])[C:3]([NH:2][CH3:1])=[C:4]2[CH:13]=[CH:12][N:11]=[C:5]12)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1 | BrCc1ccccc1 | CNc1c(C=O)cnc2[nH]ccc12 | null | O=C([O-])[O-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | 25 | 12 | To solution of 4-methylamino-1H-pyrrolo[2,3-b]pyridine-5-carbaldehyde (0.5 g, 2.86 mmol) in DMF is added Na2CO3 (900 mg, 8.6 mmol) and benzyl bromide (0.5 ml, 4.3 mmol). The reaction is stirred at room temperature for 12 hours. The reaction mixture is partitioned in 100 ml water and 100 ml ethyl acetate, extracted with ethyl acetate three times. The organic phase is combined and washed with brine, dried over Na2SO4. The crude product is purified by silica gel flash chromatography, eluted with 5% methanol in ethyl acetate to give the title compound as yellow solid. 1H NMR 400 MHz (DMSO-d6) δ 9.70 (s, 1H), 9.20 (q, 1H, J=5.2 Hz), 8.59 (s, 1H), 7.46 (m, 2H), 7.35 (m, 3H), 7.28 (d, 1H, J=2.8 Hz), 7.22 (d, 1H, J=2.4 Hz), 5.65 (s, 2H), 3.31 (d, 2H, J=2.4 Hz). MS m/z 266.2 (M+1). | CNc1c(C=O)cn(Cc2ccccc2)c2nccc1-2 | null | null | null |
538,093 | ord_dataset-1884c7bf3d544afdb8d17b5d41b90a27 | null | 2002-01-01T00:03:00 | true | O1CCCCC1[O:7][C@@H:8]1[CH2:12][C@H:11]([O:13]C2CCCCO2)[C@H:10]([CH2:20]/[CH:21]=[CH:22]\[CH2:23][CH2:24][C:25](=[O:31])[CH2:26][O:27][C:28](=[O:30])[CH3:29])[C@H:9]1/[CH:32]=[CH:33]/[C@@H:34]([O:40]C1CCCCO1)[CH2:35][CH2:36][CH2:37][CH2:38][CH3:39]>CO>[OH:7][C@@H:8]1[CH2:12][C@H:11]([OH:13])[C@H:10]([CH2:20]/[CH:21]=[CH:22]\[CH2:23][CH2:24][C:25](=[O:31])[CH2:26][O:27][C:28](=[O:30])[CH3:29])[C@H:9]1/[CH:32]=[CH:33]/[C@@H:34]([OH:40])[CH2:35][CH2:36][CH2:37][CH2:38][CH3:39] | CCCCC[C@@H](/C=C/[C@@H]1[C@@H](C/C=C\CCC(=O)COC(C)=O)[C@@H](OC2CCCCO2)C[C@H]1OC1CCCCO1)OC1CCCCO1 | null | 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 | 25 | null | A solution of the acetate of Example 25 (36 mg, 0.055 mmol) and PPTs (2 mg) in MeOH (1.0 mL) was stirred at 45° C. for 4 h. The reaction was cooled to room temperature and the solvent was removed in vacuo. The residue was diluted with EtOAc and washed with 1N HCl, saturated aqueous NaHCO3 and brine. The organic portion was dried (MgSO4), filtered and concentrated in vacuo. FCC (silica gel, 50%-100% EtOAc/hex) afforded 18 mg of the named compound. | CCCCC[C@H](O)/C=C/[C@@H]1[C@@H](C/C=C\CCC(=O)COC(C)=O)[C@@H](O)C[C@H]1O | null | 82.5 | null |
559,014 | ord_dataset-f483e698250b4da0a84f425c7bfa965a | null | 2002-01-01T00:08:00 | true | [C:1]([C:9]1[CH:10]=[C:11]([O:16][CH2:17][C@@H:18]2[CH2:21][CH2:20][N:19]2C(OC(C)(C)C)=O)[CH:12]=[N:13][C:14]=1[Cl:15])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[C:1]([C:9]1[CH:10]=[C:11]([O:16][CH2:17][C@@H:18]2[CH2:21][CH2:20][NH:19]2)[CH:12]=[N:13][C:14]=1[Cl:15])(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1 | CC(C)(C)OC(=O)N1CC[C@H]1COc1cnc(Cl)c(C(=O)c2ccccc2)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O=C(O)C(F)(F)F | ClCCl | null | null | null | null | null | null | null | null | null | 0 | 0.75 | 5-benzoyl-6-chloro-3-(1-BOC-2-(S)-azetidinylmethoxy)pyridine from step 107a is dissolved in CH2Cl2 (10 mL). The mixture is cooled to 0° C., TFA (10 mL) is added and the reaction is stirred for 45 minutes as it warms to room temperature. The mixture is concentrated in vacuo and taken up in a minimum amount of H2O. The aqueous mixture is basified with 15% NaOH and extracted with CH2Cl2 (200 mL), which is dried (MgSO4) and concentrated. The residue is chromatographed (silica gel) to afford the free amine. The isolated free amine is taken up in a minimum amount of Et2O, cooled to 0° C., and treated with HCl in EtOH to afford the hydrochloride salt. | O=C(c1ccccc1)c1cc(OC[C@@H]2CCN2)cnc1Cl | null | null | null |
175,229 | ord_dataset-4937da99a6a247eb90fa70f0d2eac3db | null | 1988-01-01T00:07:00 | true | C([NH:3][C@H:4]([C:9]([NH:11][C@H:12]([C:20]([OH:22])=[O:21])[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:10])[CH2:5][C:6](=[O:8])[OH:7])=O.Cl.O.[CH3:25]O>>[CH3:25][O:22][C:20](=[O:21])[C@H:12]([CH2:13][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)[NH:11][C:9](=[O:10])[C@H:4]([CH2:5][C:6](=[O:8])[OH:7])[NH2:3] | O=CN[C@@H](CC(=O)O)C(=O)N[C@@H](Cc1ccccc1)C(=O)O | CO | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | null | null | null | null | null | null | null | null | null | null | null | null | deformylating formyl-α-L-aspartyl-L-phenylalanine in the presence of hydrogen chloride, methanol and water. Then, adding methanol and hydrogen chloride directly to the resulting solution to obtain the chloride salt of α-L-aspartyl-L-phenylalanine methyl ester. | COC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](N)CC(=O)O | null | null | null |
767,601 | ord_dataset-7a8649d55889427e85b208ae89475895 | null | 2007-01-01T00:04:00 | true | [CH3:1][N:2]([CH3:52])[CH2:3][C:4]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13]2[C:21]3[C:16](=[CH:17][CH:18]=[C:19]([C:22]4[N:26]=[CH:25][N:24](C(C5C=CC=CC=5)(C5C=CC=CC=5)C5C=CC=CC=5)[N:23]=4)[CH:20]=3)[N:15](C3CCCCO3)[N:14]=2)[CH:8]=1)=[O:5]>Cl.O1CCOCC1>[NH:24]1[CH:25]=[N:26][C:22]([C:19]2[CH:20]=[C:21]3[C:16](=[CH:17][CH:18]=2)[NH:15][N:14]=[C:13]3[C:9]2[CH:8]=[C:7]([NH:6][C:4](=[O:5])[CH2:3][N:2]([CH3:1])[CH3:52])[CH:12]=[CH:11][CH:10]=2)=[N:23]1 | CN(C)CC(=O)Nc1cccc(-c2nn(C3CCCCO3)c3ccc(-c4ncn(C(c5ccccc5)(c5ccccc5)c5ccccc5)n4)cc23)c1 | 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 | 3 | 2-(Dimethylamino)-N-(3-{1-perhydro-2H-pyran-2-yl-5-[1-(triphenylmethyl)(1,2,4-triazol-3-yl)](1H-indazol-3-yl)}phenyl)acetamide was dissolved in 4 mL of 4.0 N HCl in 1,4-dioxane and the reaction was stirred at room temperature for 3 hours. After neutralization with aqueous NaHCO3, the reaction mixture was evaporated to dryness and purified by preparatory HPLC. (0.023 g, 13% yield over 2 steps): 1H NMR (CD3OD) δ 8.7 (d, 1H), 8.32 (br s, 1H), 8.17 (t, 1H), 8.05 (dd, 1H), 7.7 (t, 2H), 7.6 (dd, 1H), 7.4 (t, 1H), 3.18 (s, 2H), 2.38 (s, 6H); ES-MS (m/z) 362 [M+H]+. | CN(C)CC(=O)Nc1cccc(-c2n[nH]c3ccc(-c4nc[nH]n4)cc23)c1 | null | 13 | null |
1,285,664 | ord_dataset-d5c54236ecd94d61aaa071461bcfc426 | null | 2013-01-01T00:04:00 | true | [C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([CH2:13][OH:14])[CH:10]2[O:15][CH2:16][C:17]([O:20][CH3:21])([O:18][CH3:19])[CH:9]12)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([CH:13]=[O:14])[CH:10]2[O:15][CH2:16][C:17]([O:20][CH3:21])([O:18][CH3:19])[CH:9]12)=[O:7])([CH3:4])([CH3:3])[CH3:2] | COC1(OC)COC2C(CO)CN(C(=O)OC(C)(C)C)C21 | null | null | CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21 | 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 | 0.67 | To a solution of the alcohol 1g (370 mg, 1.22 mmol) dissolved in dry DCM (10 mL) was added Dess Martin periodinane (673 mg, 1.59 mmol). The reaction was stirred for 40 minutes and then quenched by addition of 10 mL of 10% Na2S2O3: NaHCO3(sat) 1:1. The solution was diluted with DCM (50 mL) and extracted with a 1:1 mixture of 10% Na2S2O3: NaHCO3(sat) (50 mL). The organic phase was dried with Na2SO4, filtered and evaporated. The crude product was purified by flash chromatography (heptane: ethyl acetate (2:1) which gave the title compound (290 mg, 79%). | COC1(OC)COC2C(C=O)CN(C(=O)OC(C)(C)C)C21 | null | 78.9 | null |
1,063,735 | ord_dataset-ffbef48837674f39816de887b5dc8bae | null | 2011-01-01T00:06:00 | true | [Cl:1][C:2]1[CH:10]=[CH:9][C:8]([Cl:11])=[CH:7][C:3]=1[C:4]([OH:6])=O.[CH:12]1([CH2:15][CH2:16][NH:17][C:18]([C:20]2[N:21]=[N:22][C:23]([N:26]3[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]3)=[CH:24][CH:25]=2)=[O:19])[CH2:14][CH2:13]1>>[CH:12]1([CH2:15][CH2:16][NH:17][C:18]([C:20]2[N:21]=[N:22][C:23]([N:26]3[CH2:31][CH2:30][N:29]([C:4](=[O:6])[C:3]4[CH:7]=[C:8]([Cl:11])[CH:9]=[CH:10][C:2]=4[Cl:1])[CH2:28][CH2:27]3)=[CH:24][CH:25]=2)=[O:19])[CH2:14][CH2:13]1 | O=C(NCCC1CC1)c1ccc(N2CCNCC2)nn1 | O=C(O)c1cc(Cl)ccc1Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Following the procedure of Example 9, making variations only as required to use 2,5-dichlorobenzoic acid in place of 2,5-dichlorobenzoic acid to react with 6-piperazin-1-yl-pyridazine-3-carboxylic acid (2-cyclopropylethyl)amide, the title compound was obtained as a white solid (56% yield). 1H NMR (300 MHz, CDCl3) δ 8.05, 7.96, 7.38-7.30, 6.97, 4.12-3.23, 1.50, 0.80-0.67, 0.51-0.38, 0.16-0.06. MS (ES+) m/z 448.2 (M+1). | O=C(NCCC1CC1)c1ccc(N2CCN(C(=O)c3cc(Cl)ccc3Cl)CC2)nn1 | null | null | null |
1,749,467 | ord_dataset-60a3e71da3174666a50a61dcfa611a9f | null | 2016-01-01T00:07:00 | true | [S:1]([N:11]1[CH:15]=[CH:14][C:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[CH:12]1)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2].[CH:23](=[N:25]/[S@:26]([C:28]([CH3:31])([CH3:30])[CH3:29])=[O:27])\[CH3:24]>C1COCC1>[CH3:29][C:28]([CH3:31])([S@@:26]([NH:25][C@@H:23]([C:12]1[N:11]([S:1]([C:4]2[CH:5]=[CH:6][C:7]([CH3:8])=[CH:9][CH:10]=2)(=[O:2])=[O:3])[CH:15]=[CH:14][C:13]=1[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH3:24])=[O:27])[CH3:30] | C/C=N/[S@@](=O)C(C)(C)C | Cc1ccc(S(=O)(=O)n2ccc(C(=O)OC(C)(C)C)c2)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | null | 0.75 | To a solution of tert-butyl 1-tosyl-1H-pyrrole-3-carboxylate (,287a 1.67 g, 5.20 mmol) in 40 mL of THF at −78° C. was added LDA(Aldrich) (1.7 M solution in heptane/THF/ethylbenzene, 3.67 mL, 6.24 mmol) slowly dropwise. After 45 min, a solution of (S,E)-N-ethylidene-2-methylpropane-2-sulfinamide (Prepared according to PCT Int. Appl., WO2005103020; 0.765 g, 5.20 mmol) in THF was added slowly dropwise via syringe over several min. After 15 min, the acetone/dry ice bath was removed and the reaction was quenched by dropwise addition of saturated aq. NH4Cl and Et2O. The organic layer was washed with saturated aq. NH4Cl once, saturated aq. NaCl once and the organics were dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The material was treated with DCM and purified by silica gel chromatography (80 g ISCO redisep gold column) using 0-50% EtOAc/hexanes. The product-containing fractions were concentrated to afford tert-butyl 2-((R)-1-((S)-1,1-dimethylethylsulfinamido)ethyl)-1-tosyl-1H-pyrrole-3-carboxylate (287b; 1.05 g, 2.24 mmol, 43% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 7.73 (2H, d, J=8.2 Hz), 7.28-7.34 (3H, m), 6.58 (1H, d, J=3.3 Hz), 5.95 (1H, d, J=9.2 Hz), 5.14 (1H, br. s.), 2.43 (3H, s), 1.50-1.54 (12H, m), 0.96 (9H, s). m/z (ESI, +ve) 469.1 (MA-1)11. | Cc1ccc(S(=O)(=O)n2ccc(C(=O)OC(C)(C)C)c2[C@@H](C)N[S@@](=O)C(C)(C)C)cc1 | null | 43.1 | null |
1,070,270 | ord_dataset-5df93261afc143c3ae919a57ff4fc1d4 | null | 2011-01-01T00:07:00 | true | [CH2:1]([O:8][C:9]1[CH:18]=[CH:17][CH:16]=[C:15]2[C:10]=1[CH:11]=[C:12]([C:19]([O:21]CC)=[O:20])[CH:13]=[N:14]2)C1C=CC=CC=1.[Li+].[OH-]>C1COCC1.O>[CH3:1][O:8][C:9]1[CH:18]=[CH:17][CH:16]=[C:15]2[C:10]=1[CH:11]=[C:12]([C:19]([OH:21])=[O:20])[CH:13]=[N:14]2 | CCOC(=O)c1cnc2cccc(OCc3ccccc3)c2c1 | null | null | [Li+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | O | null | null | null | null | null | null | null | null | null | null | null | A solution of ethyl 5-methoxyquinoline-3-carboxylate (2.31 g, 10 mmol) prepared in stage B of example 2 and LiOH (0.4 g, 20 mmol) in THF (20 mL) and water (0.5 mL) was refluxed for 2 hours. After cooling, the solvents were evaporated under vacuum. The solid residue was used in the next step without further purification. | COc1cccc2ncc(C(=O)O)cc12 | null | null | null |
880,191 | ord_dataset-3592bd645cd143ee8274cd0d834ae581 | null | 2009-01-01T00:05:00 | true | [CH3:1][C:2]1([OH:8])[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.Br[CH2:10][CH2:11][Cl:12]>>[Cl:12][CH2:11][CH2:10][N:5]1[CH2:6][CH2:7][C:2]([CH3:1])([OH:8])[CH2:3][CH2:4]1 | ClCCBr | CC1(O)CCNCC1 | null | null | null | null | null | null | null | 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-methylpiperidin-4-ol (made via literature methods) and 1-bromo-2-chloroethane are reacted using the procedure for Example OO to afford 1-(2-chloroethyl)-4-methylpiperidin-4-ol. | CC1(O)CCN(CCCl)CC1 | null | null | null |
1,676,691 | ord_dataset-9cc455db05a444779921f786a45b21a6 | null | 2015-01-01T00:12:00 | true | [NH2:1][C:2]1([C:6]2[CH:11]=[CH:10][C:9]([C:12]3[C:13]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)=[CH:14][C:15]4[N:20]([CH2:21][CH2:22][C:23]#N)[C:19](=[O:25])[CH2:18][O:17][C:16]=4[N:26]=3)=[CH:8][CH:7]=2)[CH2:5][CH2:4][CH2:3]1.[C:33](OC(=O)NC1(C2C=CC(C3C(C4C=CC=CC=4)=CC4N(CCC)C(=O)COC=4N=3)=CC=2)CCC1)(C)(C)C>>[NH2:1][C:2]1([C:6]2[CH:7]=[CH:8][C:9]([C:12]3[C:13]([C:27]4[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=4)=[CH:14][C:15]4[N:20]([CH2:21][CH:22]([CH3:33])[CH3:23])[C:19](=[O:25])[CH2:18][O:17][C:16]=4[N:26]=3)=[CH:10][CH:11]=2)[CH2:5][CH2:4][CH2:3]1 | CCCN1C(=O)COc2nc(-c3ccc(C4(NC(=O)OC(C)(C)C)CCC4)cc3)c(-c3ccccc3)cc21 | N#CCCN1C(=O)COc2nc(-c3ccc(C4(N)CCC4)cc3)c(-c3ccccc3)cc21 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Following the procedure for 3-(6-(4-(1-aminocyclobutyl)phenyl)-2-oxo-7-phenyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-1-yl)propanenitrile, tert-butyl(1-(4-(2-oxo-7-phenyl-1-propyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)phenyl)cyclobutyl)carbamate (50 mg, 0.078 mmol) was reacted to afford the title compound (34.5 mg). 1H NMR (500 MHz, CH3OD) 7.57 (1H, s), 7.38-7.42 (4H, m), 7.30-32 (3H, m), 7.21-7.2 (2H, m), 4.97 (2H, s), 3.92 (2H, d), 2.73-2.79 (2H, m), 2.54-2.60 (2H, m), 2.22-2.25 (1H, m), 2.13-2.16 (1H, m), 1.95-1.99 (1H, m), 1.0 (6H, d). LCMS (method D) RT: 0.93, M+H+=428.2. | CC(C)CN1C(=O)COc2nc(-c3ccc(C4(N)CCC4)cc3)c(-c3ccccc3)cc21 | null | null | null |
1,225,380 | ord_dataset-cde802cdb7434a5f82a22981ccaefc4e | null | 2012-01-01T00:11:00 | true | C(=O)([O-])[O-].[K+].[K+].[NH2:7][CH:8]1[CH2:13][C:12]([CH3:15])([CH3:14])[N:11]([CH3:16])[C:10]([CH3:18])([CH3:17])[CH2:9]1.[C:19]([C:21]1[N:26]=[CH:25][C:24]([C:27]2[C:39]3[C:38]4[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=4)[N:32]([C:40]4[CH:52]=[CH:51][C:43]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])=[C:42](F)[CH:41]=4)[C:31]=3[CH:30]=[CH:29][CH:28]=2)=[CH:23][CH:22]=1)#[N:20]>CS(C)=O.O>[C:19]([C:21]1[N:26]=[CH:25][C:24]([C:27]2[C:39]3[C:38]4[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=4)[N:32]([C:40]4[CH:41]=[CH:42][C:43]([C:44]([O:46][C:47]([CH3:48])([CH3:49])[CH3:50])=[O:45])=[C:51]([NH:7][CH:8]5[CH2:9][C:10]([CH3:18])([CH3:17])[N:11]([CH3:16])[C:12]([CH3:14])([CH3:15])[CH2:13]5)[CH:52]=4)[C:31]=3[CH:30]=[CH:29][CH:28]=2)=[CH:23][CH:22]=1)#[N:20] | CN1C(C)(C)CC(N)CC1(C)C | CC(C)(C)OC(=O)c1ccc(-n2c3ccccc3c3c(-c4ccc(C#N)nc4)cccc32)cc1F | null | O=C([O-])[O-] | [K+] | 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 | 90 | null | 0.95 g of potassium carbonate and 7.8 ml of 4-amino-1,2,2,6,6-pentamethylpiperidine are successively added to a solution of 1.06 g of 2-methylpropan-2-yl 4-[4-(6-cyanopyridin-3-yl)-9H-carbazol-9-yl]-2-fluorobenzoate, obtained in stage 1 of Example 49, in 8 ml of dimethyl sulphoxide. The reaction mixture is heated at 90° C. for 2 hours and 15 minutes in a microwave, and then diluted with distilled water. The aqueous phase is extracted twice with ethyl acetate and the combined organic phases are washed with water and a saturated solution of sodium chloride and dried over magnesium sulphate. The residue is purified by silica gel chromatography, elution being carried out with a mixture of dichloromethane and methanol (97/3 by volume), so as to give 0.8 g of 2-methylpropan-2-yl 4-[4-(6-cyanopyridin-3-yl)-9H-carbazol-9-yl]-2-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]benzoate in the form of a yellow oil, the characteristics of which are the following: | CN1C(C)(C)CC(Nc2cc(-n3c4ccccc4c4c(-c5ccc(C#N)nc5)cccc43)ccc2C(=O)OC(C)(C)C)CC1(C)C | null | null | null |
1,655,460 | ord_dataset-42cd9bc5aae3485f9a58f1527bd3abf0 | null | 2015-01-01T00:11:00 | true | [C:1]12([C:11]3[CH:16]=[CH:15][C:14]([CH2:17][OH:18])=[CH:13][C:12]=3[O:19][CH:20]([CH3:22])[CH3:21])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2>O1CCOCC1.O=[Mn]=O>[C:1]12([C:11]3[CH:16]=[CH:15][C:14]([CH:17]=[O:18])=[CH:13][C:12]=3[O:19][CH:20]([CH3:22])[CH3:21])[CH2:8][CH:7]3[CH2:9][CH:3]([CH2:4][CH:5]([CH2:6]3)[CH2:10]1)[CH2:2]2 | CC(C)Oc1cc(CO)ccc1C12CC3CC(CC(C3)C1)C2 | null | null | O=[Mn]=O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1COCCO1 | null | null | null | null | null | null | null | null | null | null | null | 6 | A mixture of the product of Step B (0.7 g) and MnO2 (1.5 g) in dioxane (20 ml) was stirred for 6 h at reflux. The mixture was filtered through Celite pad and the filtrate was evaporated to dryness to give the title compound (0.51 g, 73.4%) as creamy solid. 1H-NMR (CDCl3) 1.4 (d, 6H, J=6 Hz); 1.76 (s, 6H); 2.07 (s, 3H); 2.11 (s, 6H); 4.7-4.78 (m, 1H); 7.32-7.42 (m, 3H); 9.91 (s, 1H). | CC(C)Oc1cc(C=O)ccc1C12CC3CC(CC(C3)C1)C2 | null | 73.3 | null |
587,551 | ord_dataset-7a74d48eeefd45aba53e7258f3ae067a | null | 2003-01-01T00:04:00 | true | [Br:1][C:2]1[C:7](=[O:8])[NH:6][C:5]2[N:9]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[N:10]=[CH:11][C:4]=2[CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl.Cl[CH2:26][C:27]1[N:28]([CH3:32])[N:29]=[CH:30][N:31]=1>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[CH:11]=[N:10][N:9]([C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:5]2=[N:6][C:7]=1[O:8][CH2:26][C:27]1[N:28]([CH3:32])[N:29]=[CH:30][N:31]=1 | O=c1[nH]c2c(cnn2-c2ccccc2)cc1Br | Cn1ncnc1CCl | null | Cl | O=C([O-])[O-] | [Cs+] | 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 | null | To a solution of 5-bromo-1,7-dihydro-1-phenylpyrazolo[3,4-b]pyridin-6-one (0.29 g, 1.0 mmol) in DMF (4 ml) under nitrogen was added cesium carbonate (0.98 g, 3.0 mmol) followed by 3-chloromethyl-2-methyl-2H-[1,2,4]triazole hydrochloride (0.25 g, 1.5 mmol). The resulting suspension was heated at 60° C. for 17 h. The mixture was partitioned between ammonium chloride solution (saturated aqueous) and ethyl acetate. The layers were separated and the aqueous phase extracted a second time with ethyl acetate. The combined organic extracts were washed with brine, dried (MgSO4) and concentrated in vacuo to give 5-bromo-6-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)-1-phenyl-1H-pyrazolo[3,4-b]pyridine (0.40 g) of adequate purity. δH (400 MHz; CDCl3) 4.04 (3H, s), 5.70 (2H, s), 7.33-7.37 (1H, m), 7.52-7.56 (2H, m), 7.90 (1H, s), 8.06 (1H, s), 8.16-8.19 (2H, m), 8.27 (1H, s); m/z (ES+) 387 (M+H+), 385 (M+H+). | Cn1ncnc1COc1nc2c(cnn2-c2ccccc2)cc1Br | null | 103.8 | null |
531,494 | ord_dataset-7774db17e619477ea20ee621abe71257 | null | 2002-01-01T00:01:00 | true | [CH2:1]([NH:4][C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([N+:15]([O-:17])=[O:16])[CH:13]=2)[N:8]=[C:7](Cl)[N:6]=1)[CH:2]=[CH2:3].[C:19]([NH2:23])([CH3:22])([CH3:21])[CH3:20]>O>[CH2:1]([NH:4][C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([N+:15]([O-:17])=[O:16])[CH:13]=2)[N:8]=[C:7]([NH:23][C:19]([CH3:22])([CH3:21])[CH3:20])[N:6]=1)[CH:2]=[CH2:3] | CC(C)(C)N | C=CCNc1nc(Cl)nc2ccc([N+](=O)[O-])cc12 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | null | null | null | null | null | null | null | null | null | null | null | null | At 80° C. were stirred 225 mg (0.85 mmol) of 4-allylamino-2-chloro-6-nitroquinazoline and 696 mg (9.52 mmol) of t-butylamine overnight. Water was added to the reaction mixture, followed by extraction with ethyl acetate, washing with brine and drying over anhydrous sodium sulfate. After the solvent was distilled off, the residue was purified by a silica gel column to give 240 mg (yield: 93.7%) of the title compound. | C=CCNc1nc(NC(C)(C)C)nc2ccc([N+](=O)[O-])cc12 | null | 93.7 | null |
1,457,620 | ord_dataset-a86112d52cd54525a5e36d41f18aced2 | null | 2014-01-01T00:07:00 | true | [C:1]1([C:7]2[CH:8]=[C:9]([OH:33])[C:10]([NH:13]C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)=[N:11][CH:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([O-])([O-])=O.[Cs+].[Cs+].[CH3:40][O:41][C:42]1[CH:43]=[C:44]([CH:47]=[CH:48][CH:49]=1)[CH2:45]Br>C1COCC1.ClCCl>[CH3:40][O:41][C:42]1[CH:43]=[C:44]([CH:47]=[CH:48][CH:49]=1)[CH2:45][O:33][C:9]1[C:10]([NH2:13])=[N:11][CH:12]=[C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH:8]=1 | Oc1cc(-c2ccccc2)cnc1NC(c1ccccc1)(c1ccccc1)c1ccccc1 | COc1cccc(CBr)c1 | null | O=C([O-])[O-] | [Cs+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | ClCCl | null | null | null | null | null | null | null | null | null | 25 | 0.33 | To a solution of 5-phenyl-2-(trityl-amino)-pyridin-3-ol (100 mg, 0.24 mmol) in THF (3 mL) was added Cs2CO3 (79 mg, 0.24 mmol). The mixture was stirred at room temperature for 20 minutes, and then 3-methoxybenzylbromide (0.037 mL, 0.26 mmol) was added. The reaction was stirred at room temperature overnight, diluted with dichloromethane (5 mL), and filtered to remove the salts. The solvents were evaporated, and the residue was dissolved in 10% trifluoroacetic acid in dichloromethane (2 mL). The reaction was stirred for 2 hr, and evaporated. The residue was dissolved in dichloromethane, washed by sat. NaHCO3, and dried over Na2SO4. After filtration and concentration, the crude product was purified on a silica gel column eluting with methanol-dichloromethane (from 3% to 15% gradient) to provide 3-(3-methoxy-benzyloxy)-5-phenyl-pyridin-2-ylamine as a white solid (43.5 mg, 60% yield). | COc1cccc(COc2cc(-c3ccccc3)cnc2N)c1 | null | 59.2 | null |
1,449,877 | ord_dataset-a86112d52cd54525a5e36d41f18aced2 | null | 2014-01-01T00:07:00 | true | [F:1][CH:2]([F:39])[C:3]1[N:7]([C:8]2[N:13]=[C:12]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[N:11]=[C:10]([C:20]3[CH2:21][CH2:22][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:24][CH:25]=3)[N:9]=2)[C:6]2[CH:33]=[CH:34][CH:35]=[C:36]([O:37][CH3:38])[C:5]=2[N:4]=1>CO.C1COCC1.[Pd]>[F:39][CH:2]([F:1])[C:3]1[N:7]([C:8]2[N:13]=[C:12]([N:14]3[CH2:15][CH2:16][O:17][CH2:18][CH2:19]3)[N:11]=[C:10]([CH:20]3[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:31])([CH3:32])[CH3:30])=[O:27])[CH2:22][CH2:21]3)[N:9]=2)[C:6]2[CH:33]=[CH:34][CH:35]=[C:36]([O:37][CH3:38])[C:5]=2[N:4]=1 | COc1cccc2c1nc(C(F)F)n2-c1nc(C2=CCN(C(=O)OC(C)(C)C)CC2)nc(N2CCOCC2)n1 | null | null | [Pd] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | null | A solution of tert-butyl 4-[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-3,6-dihydro-1(2H)-pyridinecarboxylate (1.79 g, 3.29 mmol) in a mixture of MeOH (80 mL) and THF (80 mL) was hydrogenated over 10% Pd on carbon (100 mg). After removal of the hydrogen, the mixture was refluxed in air for additional 2 hrs. The catalyst Pd/C was removed by filtration through celite, and the solvents were removed under vacuum. Recrystallization of the residue from methanol gave tert-butyl 4-[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-1-piperidine-carboxylate: mp (MeOH) 177-179° C.; 1H NMR (CDCl3) δ 8.01 (dd, J=8.4, 0.7 Hz, 1H), 7.58 (t, JHF=53.6 Hz, 1H), 7.38 (t, J=8.2 Hz, 1H), 6.84 (d, J=7.8 Hz, 1H), 4.22 (m, 2H), 4.05 (s, 3H), 3.99 (m, 2H), 3.94 (m, 2H), 3.81 (m, 4H), 2.94-2.78 (m, 3H), 2.05 (dd, J=13.0, 1.9 Hz, 2H), 1.81 (qd, J=12.7, 4.4 Hz, 2H), 1.49 (s, 9H); Anal. Calcd. for C26H33F2N7O4: C, 57.2; H, 6.1; N, 18.0. Found: C, 57.4; H, 6.15; N, 18.1%. | COc1cccc2c1nc(C(F)F)n2-c1nc(C2CCN(C(=O)OC(C)(C)C)CC2)nc(N2CCOCC2)n1 | null | null | null |
519,404 | ord_dataset-262b40ea420c471da9b9244fe9b8f645 | null | 2001-01-01T00:10:00 | true | [O:1]([C:8]1[CH:9]=[C:10]([NH:14][NH2:15])[CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(OCC)(=O)C.Cl[C:23]([O:25][CH:26]([CH2:28][CH3:29])[CH3:27])=[O:24]>N1C=CC=CC=1>[O:1]([C:8]1[CH:9]=[C:10]([NH:14][NH:15][C:23]([O:25][CH:26]([CH3:27])[CH2:28][CH3:29])=[O:24])[CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1 | NNc1cccc(Oc2ccccc2)c1 | CCC(C)OC(=O)Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOC(C)=O | c1ccncc1 | null | null | null | null | null | null | null | null | null | 25 | 1 | To 3.0 g of 3-phenoxyphenyl hydrazine, 100 ml of ethyl acetate and 2.5 ml of pyridine were added and the resultant solution was then stirred at room temperature for 30 minutes. Then, 2.5 ml of sec-butyl chloro-formate was added dropwise to the solution and stirred for 1 hour at room temperature. The solution was then washed twice, each time with 100 ml of water. After each wash, the aqueous fraction was removed from the organic (ethyl acetate) fraction. The resulting ethyl acetate fraction was then dried over anhydrous sodium sulfate, evaporated under reduced pressure, and then purified by column chromatography on silica gel, to produce 1.5 g of 1-methylpropyl 2-(3-phenoxyphenyl)hydrazine carboxylate as an oil. | CCC(C)OC(=O)NNc1cccc(Oc2ccccc2)c1 | null | null | null |
1,763,221 | ord_dataset-0b32b90cc77b4a3db47ad263e0bbc1a8 | null | 2016-01-01T00:09:00 | true | [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:25]#[N:26])=[C:6]([C:8]2[C:13]([O:14][CH3:15])=[CH:12][N:11]([CH:16]([CH2:20][CH:21]3[CH2:23][CH2:22]3)[C:17](O)=[O:18])[C:10](=[O:24])[CH:9]=2)[CH:7]=1.[NH2:27][C:28]1[CH:40]=[CH:39][C:31]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])=[CH:30][CH:29]=1>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:25]#[N:26])=[C:6]([C:8]2[C:13]([O:14][CH3:15])=[CH:12][N:11]([CH:16]([CH2:20][CH:21]3[CH2:22][CH2:23]3)[C:17]([NH:27][C:28]3[CH:40]=[CH:39][C:31]([C:32]([O:34][C:35]([CH3:36])([CH3:37])[CH3:38])=[O:33])=[CH:30][CH:29]=3)=[O:18])[C:10](=[O:24])[CH:9]=2)[CH:7]=1 | CC(C)(C)OC(=O)c1ccc(N)cc1 | COc1cn(C(CC2CC2)C(=O)O)c(=O)cc1-c1cc(Cl)ccc1C#N | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | 420 mg (purity 92%, 1.04 mmol) of 2-[4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]-3-cyclopropylpropanoic acid (racemate) and 1.2 eq. of tert-butyl 4-aminobenzoate were reacted according to General Method 5A. Yield: 348 mg (61% of theory) | COc1cn(C(CC2CC2)C(=O)Nc2ccc(C(=O)OC(C)(C)C)cc2)c(=O)cc1-c1cc(Cl)ccc1C#N | null | null | null |
596,881 | ord_dataset-843ef38b45484f72826f5f39d8a29c4d | null | 2003-01-01T00:06:00 | true | [NH2:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][CH2:9][CH2:10][CH2:11][O:12][C:13]2[CH:14]=[CH:15][C:16]3[CH2:22][C@@H:21]([CH2:23][C:24]([O:26]CC)=[O:25])[C:20]4[CH:29]=[CH:30][CH:31]=[CH:32][C:19]=4[CH2:18][C:17]=3[CH:33]=2)[CH:3]=1.O[Li].O.C1COCC1>O>[NH2:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][CH2:9][CH2:10][CH2:11][O:12][C:13]2[CH:14]=[CH:15][C:16]3[CH2:22][C@@H:21]([CH2:23][C:24]([OH:26])=[O:25])[C:20]4[CH:29]=[CH:30][CH:31]=[CH:32][C:19]=4[CH2:18][C:17]=3[CH:33]=2)[CH:3]=1 | CCOC(=O)C[C@@H]1Cc2ccc(OCCCNc3cc(N)ccn3)cc2Cc2ccccc21 | null | null | [Li]O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | C1CCOC1 | null | null | null | null | null | null | null | null | null | 25 | 48 | A mixture of ethyl (S)-10,11-dihydro-3-[3-(4-aminopyridin-2-ylamino)-1-propyloxy]-5H-dibenzo[a,d]cycloheptene-10-acetate (2.4 g, 5 mmole), LiOH.H2O (0.3 g, 7 mmole), THF (30 mL), and H2O (10 mL) was stirred at RT for 48 hr, then was concentrated. The residue was diluted with H2O and extracted with Et2O. The Et2O layers were discarded. The aqueous layer was stirred with gentle warming under vacuum to remove residual organic solvents, then was filtered. The resulting aqueous solution was stirred at RT while the pH was slowly and carefully adjusted to 5.5-6.0 with 1.0 N HCl The mixture was stirred for 0.5 hr, then the solid was collected by suction filtration and washed with plenty of H2O. Drying in high vacuum at 60° C. gave the title compound (1.0 g, 42%) as a glassy solid: MS (ES) m/e 417.7 (M+H)+. Anal. Calcd for C25H27N3O3 1.4 HCl (468.554): C, 64.08; H, 6.11; N, 8.97. Found: C, 64.16; H, 6.20; N, 8.71. | Nc1ccnc(NCCCOc2ccc3c(c2)Cc2ccccc2[C@H](CC(=O)O)C3)c1 | null | 47.9 | null |
1,010,093 | ord_dataset-7448b89163bf426c9d9777809ce24cec | null | 2010-01-01T00:11:00 | true | C(OC(=O)[NH:7][CH2:8][C:9](=[O:44])[NH:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([N:18]2[C:22]([NH:23][C:24]([NH:26][C:27]3[CH:32]=[CH:31][C:30]([O:33][C:34]4[CH:39]=[CH:38][N:37]=[CH:36][CH:35]=4)=[CH:29][CH:28]=3)=[O:25])=[CH:21][C:20]([C:40]([CH3:43])([CH3:42])[CH3:41])=[N:19]2)=[CH:14][CH:13]=1)(C)(C)C.C(O)(C(F)(F)F)=O>C1COCC1>[NH2:7][CH2:8][C:9]([NH:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([N:18]2[C:22]([NH:23][C:24]([NH:26][C:27]3[CH:32]=[CH:31][C:30]([O:33][C:34]4[CH:35]=[CH:36][N:37]=[CH:38][CH:39]=4)=[CH:29][CH:28]=3)=[O:25])=[CH:21][C:20]([C:40]([CH3:43])([CH3:42])[CH3:41])=[N:19]2)=[CH:14][CH:13]=1)=[O:44] | CC(C)(C)OC(=O)NCC(=O)NCc1ccc(-n2nc(C(C)(C)C)cc2NC(=O)Nc2ccc(Oc3ccncc3)cc2)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | O=C(O)C(F)(F)F | null | null | null | null | null | null | null | null | null | 25 | 18 | To a solution of {[4-(3-tert-butyl-5-{3-[4-(pyridin-4-yloxy)-phenyl]-ureido}-pyrazol-1-yl)-benzylcarbamoyl]-methyl}-carbamic acid tert-butyl ester (60 mg, 0.10 mmol) in THF (5 mL) was added TFA (3 mL), and the resulting mixture was stirred at room temperature for 18 h. The reaction mixture was partitioned between EtOAc (20 mL) and saturated NaHCO3 aqueous solution (20 mL), and the organic layer was removed and washed with brine, dried over Na2SO4, and concentrated at reduced pressure. The residue was purified by preparative TLC (90:10 CH2Cl2/MeOH) to give 10 mg (20%) of the desired product. 1H-NMR (DMSO-d6) δ 8.72 (s, 1H), 8.32 (d, J=5.7 Hz, 2H), 8.02 (s, 1H), 7.53 to 7.30 (m, 6H), 6.96 (d, J=6.6 Hz, 2H), 6.73 (d, J=6.3 Hz, 2H), 6.32 (s, 1H), 4.36 (s, 2H), 3.70 (S, 2H), 1.18 (s, 9H); MS LC-MS [M+H]+=513, RT=2.01 min. | CC(C)(C)c1cc(NC(=O)Nc2ccc(Oc3ccncc3)cc2)n(-c2ccc(CNC(=O)CN)cc2)n1 | null | 19.5 | null |
1,588,816 | ord_dataset-380e279f82154dba9e08ab51b3bdd08a | null | 2015-01-01T00:05:00 | true | [CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([NH2:8])[CH2:4][CH2:3]1.C(N(CC)CC)C.[Br:16][C:17]1[S:18][C:19]([C:23](O)=[O:24])=[C:20]([CH3:22])[N:21]=1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>O1CCCC1>[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([NH:8][C:23]([C:19]2[S:18][C:17]([Br:16])=[N:21][C:20]=2[CH3:22])=[O:24])[CH2:4][CH2:3]1 | Cc1nc(Br)sc1C(=O)O | CN1CCC(N)CC1 | null | CCN=C=NCCCN(C)C | Cl | On1nnc2ccccc21 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | CCN(CC)CC | null | null | null | null | null | null | null | null | null | 25 | 22 | To a stirred mixture of 1-methyl-4-aminopiperidine (125 μL, 114 mg, 1 mmol) and triethylamine (570 μL, 414 mg, 4.1 mmol) in anhydrous tetrahydrofuran (1.0 mL), 2-bromo-4-methyl-thiazole-5-carboxylic acid (266 mg, 1.2 mmol), (3-dimethylaminopropyl)-ethyl-carbodiimide hydrochloride (232 mg, 1.2 mmol) and 1-hydroxy-benzotriazole (164 mg, 1.2 mmol) were sequentially and the mixture was stirred at room temperature for 22 h. After dilution with dichloromethane (20 mL), the mixture was washed with water (3×10 mL), dried over MgSO4 and concentrated. In this manner the title compound (277 mg, 0.87 mmol, 87%) was obtained as a yellow solid. | Cc1nc(Br)sc1C(=O)NC1CCN(C)CC1 | null | 87 | null |
1,008,191 | ord_dataset-7448b89163bf426c9d9777809ce24cec | null | 2010-01-01T00:11:00 | true | FC(F)(F)COP([CH2:13][C:14]([O:16][CH3:17])=[O:15])(OCC(F)(F)F)=O.C1OCCOCCOCCOCCOCCOC1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].[Cl:48][C:49]1[CH:50]=[C:51]([C:59]2[N:63]=[C:62]([C:64]3[CH:71]=[CH:70][C:67]([CH:68]=O)=[CH:66][CH:65]=3)[O:61][N:60]=2)[CH:52]=[CH:53][C:54]=1[O:55][CH:56]([CH3:58])[CH3:57]>C1COCC1>[Cl:48][C:49]1[CH:50]=[C:51]([C:59]2[N:63]=[C:62]([C:64]3[CH:65]=[CH:66][C:67](/[CH:68]=[CH:13]\[C:14]([O:16][CH3:17])=[O:15])=[CH:70][CH:71]=3)[O:61][N:60]=2)[CH:52]=[CH:53][C:54]=1[O:55][CH:56]([CH3:57])[CH3:58] | COC(=O)CP(=O)(OCC(F)(F)F)OCC(F)(F)F | CC(C)Oc1ccc(-c2noc(-c3ccc(C=O)cc3)n2)cc1Cl | null | C1COCCOCCOCCOCCOCCO1 | C[Si](C)(C)[N-][Si](C)(C)C | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | -78 | null | A two-neck round bottom flask was charged with methyl 2-(bis(2,2,2-trifluoroethoxy)phosphoryl)acetate (0.235 ml, 1.109 mmol), 18-crown-6 (1465 mg, 5.54 mmol) and THF (15 ml). The mixture was then cooled to −78° C. under an atmosphere of nitrogen. Potassium bis(trimethylsilyl)amide (221 mg, 1.109 mmol) was added and the mixture stirred for a few minutes. 4-(3-(3-chloro-4-isopropoxyphenyl)-1,2,4-oxadiazol-5-yl)benzaldehyde (380 mg, 1.109 mmol) was added and the mixture stirred at −78° C. for 90 minutes and then left to warm to room temperature overnight. Reaction was quenched by the addition of saturated NH4Cl (aqueous). The mixture was separated and the aqueous layer was extracted with ether (3×10 mL). The combined organics were dried over MgSO4 and concentrated to give an off-white solid. The solid was triturated with MeOH and collected by vacuum filtration and washed with MeOH (3×10 mL). Collected solid was dried overnight in a vacuum oven to give (Z)-methyl 3-(4-(3-(3-chloro-4-isopropoxyphenyl)-1,2,4-oxadiazol-5-yl)phenyl)acrylate (325 mg, 73.5%). | COC(=O)/C=C\c1ccc(-c2nc(-c3ccc(OC(C)C)c(Cl)c3)no2)cc1 | null | 73.5 | null |
1,055,994 | ord_dataset-373415d3e0e54004837cf4831e67666f | null | 2011-01-01T00:05:00 | true | CCCC[N+](CCCC)(CCCC)CCCC.[F-].[Si]([O:26][C:27]([CH3:60])([CH3:59])[CH2:28][C:29]1[CH:30]=[CH:31][C:32]2[C:45]3[N:44]=[C:43]([C:46]4[C:51]([Br:52])=[CH:50][CH:49]=[CH:48][C:47]=4[Br:53])[NH:42][C:41]=3[C:40]3[C:35](=[CH:36][C:37]([O:54][CH2:55][CH:56]4[CH2:58][CH2:57]4)=[CH:38][CH:39]=3)[C:33]=2[CH:34]=1)(C(C)(C)C)(C)C>O>[CH:56]1([CH2:55][O:54][C:37]2[CH:36]=[C:35]3[C:40](=[CH:39][CH:38]=2)[C:41]2[NH:42][C:43]([C:46]4[C:47]([Br:53])=[CH:48][CH:49]=[CH:50][C:51]=4[Br:52])=[N:44][C:45]=2[C:32]2[CH:31]=[CH:30][C:29]([CH2:28][C:27]([CH3:60])([OH:26])[CH3:59])=[CH:34][C:33]3=2)[CH2:57][CH2:58]1 | CC(C)(Cc1ccc2c(c1)c1cc(OCC3CC3)ccc1c1[nH]c(-c3c(Br)cccc3Br)nc21)O[Si](C)(C)C(C)(C)C | null | null | CCCC[N+](CCCC)(CCCC)CCCC | [F-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | null | null | null | null | null | null | null | null | null | null | null | null | TBAF (1 M in THF, 10 mL) was added to a flask containing 6-(2-{[tert-butyl(dimethyl)silyl]oxy}-2-methylpropyl)-9-(cyclopropylmethoxy)-2-(2,6-dibromophenyl)-1H-phenanthro[9,10-d]imidazole (0.223 g, 0.31 mmol) from Step 7 above, at room temperature. The resulting solution was heated at reflux for 36 h, after which water was added to the reaction mixture. The aqueous layer was extracted with ethyl acetate, the organic layer dried over MgSO4, filtered and concentrated. The crude product was used directly in the next reaction (Step 9 below). | CC(C)(O)Cc1ccc2c(c1)c1cc(OCC3CC3)ccc1c1[nH]c(-c3c(Br)cccc3Br)nc21 | null | null | null |
1,759,689 | ord_dataset-97eb2ab57fec4160922caae33b54d956 | null | 2016-01-01T00:08:00 | true | [C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:15]3[CH:16]=[N:17][N:18]([CH:20]4[CH2:22][CH2:21]4)[CH:19]=3)=[C:11](N)[CH:12]=2)[N:7]([C:23]([O:25][CH:26]([CH3:28])[CH3:27])=[O:24])[CH2:6][C@@H:5]1[CH3:29])(=[O:3])[CH3:2].C(N1C2C(=CC(C3C=CC(S(C)(=O)=O)=CC=3)=C([Br:43])C=2)N(C(OC(C)C)=O)C[C@@H]1C)(=O)C>>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:15]3[CH:16]=[N:17][N:18]([CH:20]4[CH2:22][CH2:21]4)[CH:19]=3)=[C:11]([Br:43])[CH:12]=2)[N:7]([C:23]([O:25][CH:26]([CH3:28])[CH3:27])=[O:24])[CH2:6][C@@H:5]1[CH3:29])(=[O:3])[CH3:2] | CC(=O)N1c2cc(N)c(-c3cnn(C4CC4)c3)cc2N(C(=O)OC(C)C)C[C@@H]1C | CC(=O)N1c2cc(Br)c(-c3ccc(S(C)(=O)=O)cc3)cc2N(C(=O)OC(C)C)C[C@@H]1C | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Isopropyl (S)-4-acetyl-6-bromo-7-(1-cyclopropyl-1H-pyrazol-4-yl)-3-methyl-3,4-dihydroquinoxaline-1(2H)-carboxylate was synthesized from isopropyl (S)-4-acetyl-6-amino-7-(1-cyclopropyl-1H-pyrazol-4-yl)-3-methyl-3,4-dihydroquinoxaline-1(2H)-carboxylate according to the procedure described above for isopropyl (S)-4-acetyl-6-bromo-3-methyl-7-(4-(methylsulfonyl)phenyl)-3,4-dihydroquinoxaline-1(2H)-carboxylate (Example 238). MS (ESI, pos. ion) m/z 461, 463 [M+H]+. | CC(=O)N1c2cc(Br)c(-c3cnn(C4CC4)c3)cc2N(C(=O)OC(C)C)C[C@@H]1C | null | null | null |
1,172,210 | ord_dataset-d24cc23b3db94284bb83a2ccdd9eb880 | null | 2012-01-01T00:05:00 | true | [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:19](=[O:20])[N:18]([CH3:21])[C:11]3[N:12]=[C:13](SC)[N:14]=[CH:15][C:10]=3[CH:9]=2)=[CH:4][C:3]=1[NH:22][C:23]([NH:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:35])([F:34])[F:33])[CH:27]=1)=[O:24].[CH3:36][NH2:37].C1COCC1>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:19](=[O:20])[N:18]([CH3:21])[C:11]3[N:12]=[C:13]([NH:37][CH3:36])[N:14]=[CH:15][C:10]=3[CH:9]=2)=[CH:4][C:3]=1[NH:22][C:23]([NH:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:35])([F:34])[F:33])[CH:27]=1)=[O:24] | CN | CSc1ncc2cc(-c3ccc(F)c(NC(=O)Nc4cccc(C(F)(F)F)c4)c3)c(=O)n(C)c2n1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | null | null | Using a procedure analogous to Example A1, 1-(2-fluoro-5-(8-methyl-2-(methylthio)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-6-yl)phenyl)-3-(3-(trifluoromethyl)phenyl)urea (436 mg, 0.866 mmol) and 2.00N methylamine in THF (1.93 mL, 3.85 mmol) were combined to provide 1-(2-fluoro-5-(8-methyl-2-(methylamino)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-6-yl)phenyl)-3-(3-(trifluoromethyl)phenyl)urea (141 mg, 75% yield). 1H NMR (300 MHz, DMSO-d6): δ 2.89 (s, 3 H), 3.53-3.61 (m, 3 H), 7.24-7.31 (m, 3 H), 7.49-7.51 (m, 2 H), 7.65-7.75 (br. m, 1 H), 7.79 (m, 1 H), 8.03 (s, 1 H), 8.37-8.39 (m, 1 H), 8.65-8.73 (m, 2 H), 9.40 (s, 1H); MS (ESI) m/z: 487.0 (M+H+). | CNc1ncc2cc(-c3ccc(F)c(NC(=O)Nc4cccc(C(F)(F)F)c4)c3)c(=O)n(C)c2n1 | null | 75 | null |
1,410,745 | ord_dataset-7456bda2326f4bebaa874a5474d4cc0d | null | 2014-01-01T00:03:00 | true | Cl[C:2]1[C:3]2[CH2:10][C:9](=[O:11])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[C:12]([N:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1)([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13].CCN(C(C)C)C(C)C>CC(O)C>[C:12]([N:19]1[CH2:20][CH2:21][N:22]([C:6]2[N:7]=[CH:2][C:3]3[CH2:10][C:9](=[O:11])[NH:8][C:4]=3[N:5]=2)[CH2:23][CH2:24]1)([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13] | CC(C)(C)OC(=O)N1CCNCC1 | O=C1Cc2c(Cl)ncnc2N1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(C(C)C)C(C)C | CC(C)O | null | null | null | null | null | null | null | null | null | null | 14 | A solution of 4-chloro-5,7-dihydropyrrolo[2,3-d]pyrimidin-6-one (prepared according to the literature: Li Sun et al. Bioorg. and Med. Chem. Lett. 2002, 12, 2153-2157; 690 mg, 3.7 mmol), Boc-piperazine (630 mg, 3.7 mmol), and DIEA (0.96 mL, 5.5 mmol) in 20 mL IPA was heated to reflux and stirred 14 hours, after which the reaction mixture was concentrated. The crude was purified on silica gel (1:2 DCM:EtOAc to 1:4 DCM:EtOAc gradient) to give 4-Boc-piperazin-1-yl-5,7-dihydropyrrolo[2,3-d]pyrimidin-6-one, which was used in the next step. | CC(C)(C)OC(=O)N1CCN(c2ncc3c(n2)NC(=O)C3)CC1 | null | null | null |
939,828 | ord_dataset-90b0aa1f83334a02919b2be3a1c04542 | null | 2010-01-01T00:02:00 | true | [CH2:1]([N:7]([CH3:51])[C:8]([CH:10]1[CH:14]([C:15](=[O:32])[NH:16][C:17]2([C:22]([NH:24][S:25]([C:28]3([CH3:31])[CH2:30][CH2:29]3)(=[O:27])=[O:26])=[O:23])[CH2:19][CH:18]2C=C)[CH2:13][CH:12]([O:33][C:34](=[O:50])[NH:35][C:36]2[CH:41]=[C:40]([CH3:42])[CH:39]=[CH:38][C:37]=2[C:43]2[S:44][C:45](CC)=[CH:46][N:47]=2)[CH2:11]1)=[O:9])[CH2:2][CH2:3][CH2:4][CH:5]=[CH2:6].[CH:52]1(S(O)(=O)=O)C[CH2:53]1>>[CH3:51][N:7]1[C:8](=[O:9])[CH:10]2[CH:14]([CH2:13][CH:12]([O:33][C:34](=[O:50])[NH:35][C:36]3[CH:41]=[C:40]([CH3:42])[CH:39]=[CH:38][C:37]=3[C:43]3[S:44][CH:45]=[C:46]([CH2:52][CH3:53])[N:47]=3)[CH2:11]2)[C:15](=[O:32])[NH:16][C:17]2([C:22]([NH:24][S:25]([C:28]3([CH3:31])[CH2:30][CH2:29]3)(=[O:26])=[O:27])=[O:23])[CH:19]([CH2:18]2)[CH:6]=[CH:5][CH2:4][CH2:3][CH2:2][CH2:1]1 | O=S(=O)(O)C1CC1 | C=CCCCCN(C)C(=O)C1CC(OC(=O)Nc2cc(C)ccc2-c2ncc(CC)s2)CC1C(=O)NC1(C(=O)NS(=O)(=O)C2(C)CC2)CC1C=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 | null | The procedure described in Example 18-10 was followed, but using the compound prepared in Example 22 (112) (22 mg, 30 μmol) instead of the corresponding cyclopropanesulphonic acid derivative, which gave the title compound (2.1 mg, 10%). LC/MS (Method I): tr=2.41 min, >95%, m/z (ESI+)=712 (MH+). | CCc1csc(-c2ccc(C)cc2NC(=O)OC2CC3C(=O)NC4(C(=O)NS(=O)(=O)C5(C)CC5)CC4C=CCCCCN(C)C(=O)C3C2)n1 | null | 10 | null |
714,502 | ord_dataset-c8a367b56b4f406b878f51867b157d19 | null | 2006-01-01T00:06:00 | true | Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([NH2:9])=[O:8].[Cu](C#N)[C:12]#[N:13].N>CN(C=O)C>[C:12]([C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([NH2:9])=[O:8])#[N:13] | N#C[Cu]C#N | NC(=O)c1cncc(Br)c1 | null | N | 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 | 140 | 24 | 5-Bromonicotinamide (905 mg) and copper cyanide (630 mg) were suspended in DMF (15 ml) and the mixture was stirred at 140° C. for 24 hrs. Aqueous ammonia was added to the reaction mixture at room temperature and the solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography (eluent, methanol:ethyl acetate=1:10) for purification to give the title compound (110 mg) as a colorless powder. | N#Cc1cncc(C(N)=O)c1 | null | 16.6 | null |
172,564 | ord_dataset-7860c6f563014da8948ede63b7110bde | null | 1988-01-01T00:05:00 | true | [CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:20]([O:22]C)=[O:21])[C:12](=[C:17]([CH3:19])[CH:18]=1)[C:13]([O:15][CH3:16])=[O:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>[OH-].[Na+].COCCOC>[C:13]([C:12]1[C:17]([CH3:19])=[CH:18][C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[CH:10][C:11]=1[C:20]([OH:22])=[O:21])([O:15][CH3:16])=[O:14] | COC(=O)c1cc(OCc2ccccc2)cc(C)c1C(=O)OC | null | null | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | COCCOC | null | null | null | null | null | null | null | null | null | null | null | null | A solution of dimethyl 4-benzyloxy-6-methyl-phthalate (1.5 gm) in sodium hydroxide (2% solution, 12 ml) and 1,2-dimethoxyethane (12 ml) was stirred at room temperature for 4 hours. The solvent was removed under reduced pressure. The aqueous solution was washed with ethyl acetate (3×125 ml). The organic extract was dried over magnesium sulphate and evaporated to give a solid. This solid was recrystallized from ethyl acetate: pet. ether 30-60 to yield 2-carbomethoxy-3-methyl-5-benzyloxy-benzoic acid (750 mg), m.p. 132°-133° C., IR (KBr): 2500-3200, 1725, 1685, 1600 cm-1. Anal. calcd. for C17H16O5 : C, 67.99, H, 5.37. Found: C, 68.01, H, 5.42. | COC(=O)c1c(C)cc(OCc2ccccc2)cc1C(=O)O | null | 52.3 | null |
1,607,667 | ord_dataset-9cecb3a8d3b9494191b28dcefea66af2 | null | 2015-01-01T00:07:00 | true | [C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:13][CH2:12][C@H:11]([O:14][C:15]3[CH:16]=[C:17]([CH:21]=[CH:22][CH:23]=3)[C:18]([OH:20])=O)[CH2:10]2)=[CH:5][CH:4]=1)#[N:2].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[CH3:38][N:39]1[CH2:44][CH2:43][C:42]2[N:45]=[C:46]([NH2:48])[S:47][C:41]=2[CH2:40]1>CN(C=O)C>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:13][CH2:12][C@H:11]([O:14][C:15]3[CH:16]=[C:17]([CH:21]=[CH:22][CH:23]=3)[C:18]([NH:48][C:46]3[S:47][C:41]4[CH2:40][N:39]([CH3:38])[CH2:44][CH2:43][C:42]=4[N:45]=3)=[O:20])[CH2:10]2)=[CH:5][CH:4]=1)#[N:2] | N#Cc1ccc(N2CC[C@H](Oc3cccc(C(=O)O)c3)C2)cc1 | CN1CCc2nc(N)sc2C1 | null | On1nnc2ccccc21 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCCl | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | 1 | Dissolve 3-[(S)-1-(4-cyano-phenyl)-pyrrolidin-3-yloxy]-benzoic acid (80.2 mg, 0.26 mmol), EDC (99.2 mg, 0.52 mmol) and HOBT (79.6 mg, 0.52 mmol) into 2 mL of DMF. The mixture is stirred for 1 h. Add 5-methyl-4,5,6,7-tetrahydro-thiazolo[5,4-c]pyridin-2-ylamine (46.5 mg, 0.28 mmol) to the mixture and place in a 60° C. bath with an Ar stream blowing over it. Stir mixture for 14 h resulting in a concentrated residue. LC-MS analysis indicates the desired product. Dissolve into 5 mL of DMF and purify via the Gilson Prep HPLC system (5%-80% CH3CN/H2O) to give 59.4 mg of the title compound, MS, electrospray 560.58 (M+H), rt 6.01 min. | CN1CCc2nc(NC(=O)c3cccc(O[C@H]4CCN(c5ccc(C#N)cc5)C4)c3)sc2C1 | null | null | null |
1,188,857 | ord_dataset-9cd817a75dfc4fe7ad19d4232772d5ff | null | 2012-01-01T00:07:00 | true | [C:1]1([CH3:29])[CH:6]=[C:5]([CH3:7])[CH:4]=[C:3]([CH3:8])[C:2]=1[O:9][C:10]1[C:11]2[N:27]([CH3:28])[CH:26]=[CH:25][C:12]=2[N:13]=[C:14]([NH:16][C:17]2[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[CH:19][CH:18]=2)[N:15]=1.C1C(=O)N([Cl:37])C(=O)C1>C(Cl)Cl>[Cl:37][C:25]1[C:12]2[N:13]=[C:14]([NH:16][C:17]3[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[CH:19][CH:18]=3)[N:15]=[C:10]([O:9][C:2]3[C:1]([CH3:29])=[CH:6][C:5]([CH3:7])=[CH:4][C:3]=3[CH3:8])[C:11]=2[N:27]([CH3:28])[CH:26]=1 | Cc1cc(C)c(Oc2nc(Nc3ccc(C#N)cc3)nc3ccn(C)c23)c(C)c1 | O=C1CCC(=O)N1Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | null | null | To a solution of 4-(4-(mesityloxy)-5-methyl-5H-pyrrolo[3,2-d]pyrimidin-2-ylamino)benzonitrile (17.3 mg, 0.05 mmol) in CH2Cl2 (5 mL) was added NCS (6.03 mg, 0.05 mmol) and the resultant mixture was refluxed for 16 h. After completion of the reaction, the solvent was concentrated and purified by preparative TLC, eluting with hexanes:ethyl acetate (3:1), to give the product as an off-white solid (3.4 mg, 6%). | Cc1cc(C)c(Oc2nc(Nc3ccc(C#N)cc3)nc3c(Cl)cn(C)c23)c(C)c1 | null | 16.3 | null |
1,769,180 | ord_dataset-0b32b90cc77b4a3db47ad263e0bbc1a8 | null | 2016-01-01T00:09:00 | true | [NH2:1][C:2](=[O:25])[C:3]([NH:5][C:6]1[CH:11]=[C:10]([C:12]2[S:13][CH:14]=[CH:15][CH:16]=2)[CH:9]=[CH:8][C:7]=1[NH:17]C(=O)OC(C)(C)C)=[O:4].C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:17][C:7]1[CH:8]=[CH:9][C:10]([C:12]2[S:13][CH:14]=[CH:15][CH:16]=2)=[CH:11][C:6]=1[NH:5][C:3](=[O:4])[C:2]([NH2:1])=[O:25] | CC(C)(C)OC(=O)Nc1ccc(-c2cccs2)cc1NC(=O)C(N)=O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O=C(O)C(F)(F)F | ClCCl | null | null | null | null | null | null | null | null | null | 25 | 2 | To a solution of tert-butyl (2-(2-amino-2-oxoacetamido)-4-(thiophen-2-yl)phenyl)carbamate (0.1 g, 0.28 mmol) in DCM (3 mL) was added TFA (1 mL, 13 mmol) at 0° C. The reaction was warmed to room temperature and stirred for 2 h. The reaction was then concentrated under reduced pressure. The residue was basified with a saturated aqueous solution of Na2CO3. The obtained solid was filtered, washed with water and ether then dried to afford N1-(2-amino-5-(thiophen-2-yl)phenyl)oxalamide (40 mg, 55% yield). ESI+ MS: m/z 262 ([M+H]+), 1H NMR (500 MHz, d6-DMSO): δ 9.89 (s, 1H), 8.24 (s, 1H), 7.94 (s, 1H), 7.59 (d, J=2.0 Hz, 1H), 7.6 (d, J=5 Hz, 1H), 7.29-7.26 (m, 1H), 7.23 (d, J=4.0 Hz, 1H), 7.05 (t, J=4.0 Hz, 1H), 6.80 (d, J=9.0 Hz, 1H), 5.16 (s, 2H). | NC(=O)C(=O)Nc1cc(-c2cccs2)ccc1N | null | 54.7 | null |
491,942 | ord_dataset-3f9174c7efcb4f31becbd3516cde9572 | null | 2001-01-01T00:02:00 | true | [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][CH:12]([NH:15][C:16](=O)[CH2:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:11][CH2:10]2)=[CH:5][CH:4]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([N:9]2[CH2:10][CH2:11][CH:12]([NH:15][CH2:16][CH2:17][CH2:18][C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH2:13][CH2:14]2)=[CH:7][CH:8]=1 | COc1ccc(N2CCC(NC(=O)CCc3ccccc3)CC2)cc1 | null | null | [Al+3] | [H-] | [Li+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Following the general procedure of example 40b, N-[1-(4-methoxy-phenyl)-piperidin-4-yl]-3-phenyl-propionamide (1.87 g, 5.53 mmol) was reduced with LiAlH4 to give [1-(4-methoxy-phenyl)-piperidin-4-yl]-(3-phenyl-propyl)-amine (1.64 g, 91%, MS: m/e=325.4 (M+H+)) as a white solid. | COc1ccc(N2CCC(NCCCc3ccccc3)CC2)cc1 | null | 91.4 | null |
1,207,827 | ord_dataset-fb72428f30234761b4216139dc228d0c | null | 2012-01-01T00:09:00 | true | [Br:1][C:2]1[C:3]([O:10][CH3:11])=[N+:4]([O-])[C:5]([CH3:8])=[CH:6][CH:7]=1.[C:12]([O:15][C:16](=O)C)(=[O:14])C>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:12]([O:15][CH3:16])=[O:14])=[N:4][C:3]=1[O:10][CH3:11] | CC(=O)OC(C)=O | COc1c(Br)ccc(C)[n+]1[O-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | step c—A solution of 357b (0.47 g) and acetic anhydride (4.0 mL) was heated at 120° C. for 2 h, The reaction mixture was concentrated in vacuo and purified on a SiO2 column eluting with 5% EtOAc/hexane to afford methyl 5-bromo-6-methoxy-pyridin-2-yl-acetate (357c). | COC(=O)Cc1ccc(Br)c(OC)n1 | null | null | null |
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