original_index int64 2 1.77M | extracted_from_file stringclasses 489 values | date_of_experiment timestamp[ns]date | grant_date timestamp[ns]date 1976-01-01 00:01:00 2016-01-01 00:09:00 | is_mapped bool 1 class | rxn_str stringlengths 87 6.12k | reactant_000 stringlengths 1 902 | reactant_001 stringlengths 1 902 ⌀ | reactant_002 null | agent_000 stringlengths 1 540 ⌀ | agent_001 stringlengths 1 852 ⌀ | agent_002 stringlengths 1 247 ⌀ | agent_003 null | agent_004 null | agent_005 null | agent_006 null | agent_007 null | agent_008 null | agent_009 null | agent_010 null | agent_011 null | agent_012 null | agent_013 null | agent_014 null | agent_015 null | agent_016 null | solvent_000 stringclasses 446 values | solvent_001 stringclasses 405 values | solvent_002 null | solvent_003 null | solvent_004 null | solvent_005 null | solvent_006 null | solvent_007 null | solvent_008 null | solvent_009 null | solvent_010 null | temperature float64 -230 30.1k ⌀ | rxn_time float64 0 2.16k ⌀ | procedure_details stringlengths 8 24.5k | product_000 stringlengths 1 484 | product_001 null | yield_000 float64 0 90,205,156,600B ⌀ | yield_001 float64 0 100M ⌀ |
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823,929 | ord_dataset-0ca5627a13c049a99463095023b09fe5 | null | 2008-01-01T00:06:00 | true | [Br:1][C:2]1[CH:3]=[C:4]([O:8][CH3:9])[CH:5]=[CH:6][CH:7]=1.[Cl:10][S:11](O)(=[O:13])=[O:12]>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([S:11]([Cl:10])(=[O:13])=[O:12])=[C:4]([O:8][CH3:9])[CH:3]=1 | COc1cccc(Br)c1 | O=S(=O)(O)Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | 0 | 1 | To chlorosulfonic acid (20 ml) at 0° C. was added dropwise 3-bromoanisole (18.7 g, 0.1 mol) at such a rate that the internal temperature remained below 5° C. The mixture was stirred at 0° C. for 1 hour and added dropwise to crushed ice. The mixture was extracted with ethyl acetate and the combined organic layers were washed with water and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by chromatography on silica gel (1:25 ethyl acetate:pentane) to afford the title compound; 4-bromo-2-(methyloxy)benzenesulfonyl chloride (D30) 1H-NMR (CDCl3) δ 7.81 (1H, d, J 8 Hz), 7.28 (1H, d, J 2 Hz), 7.26 (1H, dd, J 8, 2 Hz), 4.07 (3H, s) and an isomer; 2-bromo-4-(methyloxy)benzenesulfonyl chloride 1H-NMR (CDCl3) δ 8.12 (1H, d), 7.33 (1H, d), 6.97 (1H, dd), 3.92 (3H, s). | COc1cc(Br)ccc1S(=O)(=O)Cl | null | null | null |
1,725,948 | ord_dataset-36057d699ac5449e9c37eb99abf78b03 | null | 2016-01-01T00:05:00 | true | Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([Cl:12])[N:10]=2)[N:5]=[CH:4][C:3]=1[C:13](=[O:15])[CH3:14].[CH3:16][N:17]1[CH2:22][CH2:21][CH:20]([CH2:23][NH2:24])[CH2:19][CH2:18]1>>[Cl:12][C:9]1[N:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]=[CH:4][C:3]([C:13](=[O:15])[CH3:14])=[C:2]2[NH:24][CH2:23][CH:20]1[CH2:21][CH2:22][N:17]([CH3:16])[CH2:18][CH2:19]1 | CN1CCC(CN)CC1 | CC(=O)c1cnc2ccc(Cl)nc2c1Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Following general procedure I, 1-(4,6-dichloro-1,5-naphthyridin-3-yl)ethanone (250 mg, 1.0 mmol) was reacted with (1-methylpiperidin-4-yl)methanamine (160 mg, 1.3 mmol) to afford the desired product (170 mg, 49%) as a light yellow-brown solid: 1H NMR (500 MHz, CDCl3) δ 11.06 (br s, 1H), 8.95 (s, 1H), 8.10 (d, J=8.8 Hz, 1H), 7.53 (d, J=8.7 Hz, 1H), 4.13 (t, J=6.4 Hz, 2H), 2.99-2.92 (m, 2H), 2.69 (s, 3H), 2.32 (s, 3H), 2.07-1.98 (m, 2H), 1.97-1.89 (m, 2H), 1.85-1.75 (m, 1H), 1.57-1.47 (m, 2H); ESI MS m/z 333 [M+H]+ | CC(=O)c1cnc2ccc(Cl)nc2c1NCC1CCN(C)CC1 | null | 51.1 | null |
626,937 | ord_dataset-e44331dc51de453ca14b7032593c1958 | null | 2004-01-01T00:02:00 | true | [CH2:1]([O:8][C:9]1[CH:16]=[CH:15][C:12]([CH:13]=O)=[C:11]([NH:17][CH2:18][C@@H:19]([OH:21])[CH3:20])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N:22]([O-])=O.[Na+]>C(O)(=O)C.O.[Zn]>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:12]([CH:13]=[N:22][N:17]2[CH2:18][C@@H:19]([OH:21])[CH3:20])=[CH:15][CH:16]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1 | C[C@H](O)CNc1cc(OCc2ccccc2)ccc1C=O | O=N[O-] | null | [Na+] | [Zn] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(=O)O | O | null | null | null | null | null | null | null | null | null | 25 | 0.83 | To a mixture of the product from Step C (16.0 g, 56.1 mmol) in acetic acid/water (150 mL/30 mL) at 0° C. was added sodium nitrite (7.75 g, 112 mmol) in portions over 40 min. The mixture was stirred for 50 min, cooled (ice bath), and zinc (14.7 g, 224 mmol) was added in portions. After 1 h the suspension was warmed to room temperature and more zinc was added (14.7 g, 224 mmol). The mixture was stirred for 1 h, concentrated, and extracted with EtOAc (2×300 mL). The extracts were filtered through a filter-aide, and the filtrate was washed with saturated aqueous disodium hydrogen phosphate (to pH 8) and brine, dried, and purifed by chromatrography (silica, 25% EtOAc/hexane) to afford an oil (7.01 g, 44%). | C[C@H](O)Cn1ncc2ccc(OCc3ccccc3)cc21 | null | 44.3 | null |
206,257 | ord_dataset-dd1de64954674e17b4b690cac09dc67b | null | 1990-01-01T00:04:00 | true | [Cl:1]N1C(=O)CCC1=O.[CH3:9][N:10]1[C:14]2=[CH:15][N:16]3[C:30]4[C:25](=[CH:26][CH:27]=[C:28]([Cl:31])[CH:29]=4)[CH:24]=[C:17]3[C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[N:13]2[CH:12]=[N:11]1.O>CN(C)C=O>[Cl:1][C:26]1[CH:27]=[C:28]([Cl:31])[CH:29]=[C:30]2[C:25]=1[CH:24]=[C:17]1[C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[N:13]3[CH:12]=[N:11][N:10]([CH3:9])[C:14]3=[CH:15][N:16]12 | CN1N=CN2C1=Cn1c(cc3ccc(Cl)cc31)-c1ccccc12 | O=C1CCC(=O)N1Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | O | null | null | null | null | null | null | null | null | null | 25 | 3 | A solution of 1.91 g N-chlorosuccinimide in 45 ml dimethylformamide was added dropwise to a solution of 3.33 g 1-methyl-12-chloro-4H-indolo[1,2-d][1,2,4]triazolo[4,3-a][1,4]benzodiazepine in 100 ml dimethylformamide. The reaction mixture was stirred for three hours at room temperature. Upon addition of water and stirring overnight, a solid precipitated. This was collected, triturated with hexane and dried to yield 1.72 g. Recrystallization from methanol/water yielded 1.17 g solid, m.p. 266°-270° C. | CN1N=CN2C1=Cn1c(cc3c(Cl)cc(Cl)cc31)-c1ccccc12 | null | 31.7 | null |
1,633,419 | ord_dataset-f0794d5ded7a4d3fab45cc3d7a89ee3d | null | 2015-01-01T00:09:00 | true | [CH:1]1[C:13]2[N:12]([C:14]3[CH:15]=[C:16]([C:33]4[O:34][C:35]([C:38]5[CH:43]=[CH:42][CH:41]=[C:40]([O:44]C)[CH:39]=5)=[N:36][N:37]=4)[CH:17]=[C:18]([N:20]4[C:32]5[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=5[C:26]5[C:21]4=[CH:22][CH:23]=[CH:24][CH:25]=5)[CH:19]=3)[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.B(Br)(Br)Br.C(=O)=O.CC(C)=O>ClCCl>[CH:22]1[C:21]2[N:20]([C:18]3[CH:17]=[C:16]([C:33]4[O:34][C:35]([C:38]5[CH:39]=[C:40]([OH:44])[CH:41]=[CH:42][CH:43]=5)=[N:36][N:37]=4)[CH:15]=[C:14]([N:12]4[C:13]5[CH:1]=[CH:2][CH:3]=[CH:4][C:5]=5[C:6]5[C:11]4=[CH:10][CH:9]=[CH:8][CH:7]=5)[CH:19]=3)[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[C:26]=2[CH:25]=[CH:24][CH:23]=1 | COc1cccc(-c2nnc(-c3cc(-n4c5ccccc5c5ccccc54)cc(-n4c5ccccc5c5ccccc54)c3)o2)c1 | null | null | BrB(Br)Br | O=C=O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | CC(C)=O | null | null | null | null | null | null | null | null | null | 0 | 5.5 | To a solution of 2-(3,5-dicarbazol-9-ylphenyl)-5-(3-methoxyphenyl)-1,3,4-oxadiazole (0.95 g, 1.63 mmol) in dichloromethane (20.0 ml) was dropwise added BBr3 (7.0 ml, 1M in dichloromethane) at −78° C. (dry-ice/acetone) under nitrogen. After addition of BBr3 solution, the reaction was taken to room temperature and kept at room temperature for 5.5 h. The reaction mixture was poured into ice-water (70.0 ml). Dichloromethane was evaporated under reduced pressure. The white solid was collected by filtration. After drying under vacuum, product as white solid was obtained in 0.92 g (98.9%) yield. 1H NMR (400 MHz, DMSO-d6, δ): 10.01 (s, br, 1H, OH), 8.46 (d, J=1.6 Hz, 2H), 8.28 (d, J=8.0 Hz, 4H), 8.17 (t, J=1.6 Hz, 111), 7.66 (d, J=8.0 Hz, 4H), 7.59 (d, J=8.0 Hz, 1H), 7.50 (m, 5H), 7.34 (m, 5H), 7.00 (dd, J1=8.4 Hz, J2=2.4 Hz, 1H). MS-EI (m/z): [M]+ calcd for C38H24N4O2, 568.2. found 568.2. | Oc1cccc(-c2nnc(-c3cc(-n4c5ccccc5c5ccccc54)cc(-n4c5ccccc5c5ccccc54)c3)o2)c1 | null | null | null |
781,771 | ord_dataset-8034115bd2ec4d3e95bd3ff7cfde0bde | null | 2007-01-01T00:07:00 | true | C(OC([N:8]1[CH2:26][CH2:25][N:11]2[C:12](=[O:24])[C:13]3[C:18]([C@@H:10]2[CH2:9]1)=[CH:17][CH:16]=[CH:15][C:14]=3[O:19][C:20]([F:23])([F:22])[F:21])=O)(C)(C)C.[ClH:27]>CCOCC.O>[ClH:27].[F:23][C:20]([F:21])([F:22])[O:19][C:14]1[CH:15]=[CH:16][CH:17]=[C:18]2[C:13]=1[C:12](=[O:24])[N:11]1[CH2:25][CH2:26][NH:8][CH2:9][C@H:10]12 | CC(C)(C)OC(=O)N1CCN2C(=O)c3c(OC(F)(F)F)cccc3[C@@H]2C1 | null | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOCC | O | null | null | null | null | null | null | null | null | null | null | 1 | To a stirring solution of N-(t-butoxycarbonyl)-(R)-1,3,4,10b-tetrahydro-7-trifluoromethoxy-pyrazino[2,1-a]isoindol-6(2H)-one (181 mg, 0.5 mmol) in dry ether (5 mL) was added hydrochloric acid (1 mL). The reaction was stirred for 1 h and then conc. in vacuo to a white solid. The solid was dissolved in water and lyophilized to 147 mg of a white solid. MS (ESI) 309 (M−Cl). | O=C1c2c(OC(F)(F)F)cccc2[C@@H]2CNCCN12 | null | null | null |
888,411 | ord_dataset-d728a2f811c0424cbcdb5a84d02b93ae | null | 2009-01-01T00:06:00 | true | [CH2:1]([O:4][C@@H:5]1[CH2:10][O:9]C(C)(C)[O:7][C@H:6]1[CH:13]=[CH2:14])C=C.Cl.C([O-])(O)=O.[Na+]>CO.CCOC(C)=O>[OH:9][CH2:10][C@H:5]1[C@H:6]([OH:7])[CH:13]=[CH:14][CH2:1][O:4]1 | C=CCO[C@@H]1COC(C)(C)O[C@H]1C=C | null | null | Cl | O=C([O-])O | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOC(C)=O | CO | null | null | null | null | null | null | null | null | null | 25 | 0.5 | To a solution of trans-5-allyloxy-2,2-dimethyl-4-vinyl-[1,3]dioxane (48 mg, 0.28 mmol) in MeOH (5 mL) was added a solution of methanolic HCl (0.5 mL, prepared from 0.5 mL conc. HCl in 30 mL of MeOH). The mixture was stirred for 30 min at ambient temperature. Aqueous saturated NaHCO3 (5 mL) was added and the mixture was diluted with EtOAc (50 mL). The organic layer was washed with saturated NaHCO3 (30 mL). The aqueous layer was washed with EtOAc (30 mL×2). The combined organic layers were washed with brine, dried over Na2SO4, concentrated in vacuo, and the residue was purified by flash chromatography with 100% EtOAc. | OC[C@@H]1OCC=C[C@H]1O | null | null | null |
1,051,869 | ord_dataset-373415d3e0e54004837cf4831e67666f | null | 2011-01-01T00:05:00 | true | [CH2:1]([C:7]1[CH:8]=[C:9]([C:13]2[N:17]([CH3:18])[C:16]([C:19]([N:21]3[CH2:26][CH2:25][CH:24]([N:27]4[CH2:31][CH2:30][CH2:29][CH2:28]4)[CH2:23][CH2:22]3)=[O:20])=[C:15]([C:32]#[C:33][Si](C)(C)C)[N:14]=2)[CH:10]=[CH:11][CH:12]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].C(=O)([O-])[O-].[K+].[K+].Cl>CCO.C1COCC1>[C:32]([C:15]1[N:14]=[C:13]([C:9]2[CH:10]=[CH:11][CH:12]=[C:7]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH3:6])[CH:8]=2)[N:17]([CH3:18])[C:16]=1[C:19]([N:21]1[CH2:26][CH2:25][CH:24]([N:27]2[CH2:28][CH2:29][CH2:30][CH2:31]2)[CH2:23][CH2:22]1)=[O:20])#[CH:33] | CCCCCCc1cccc(-c2nc(C#C[Si](C)(C)C)c(C(=O)N3CCC(N4CCCC4)CC3)n2C)c1 | null | null | Cl | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | CCO | null | null | null | null | null | null | null | null | null | 25 | 18 | To a solution of 0.52 g (1.00 mmol) of [2-(3-hexyl-phenyl)-3-methyl-5-trimethylsilanylethynyl-3H-imidazol-4-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone (example 12) in 10 ml EtOH:THF 5:1 was added 0.277 g (2.0 mmol) of solid potassium carbonate and the reaction mixture was stirred at RT for 18 hours. It was then poured into crashed ice, acidified with HCl (25% in water) and extracted twice with CH2Cl2; the organic phases were washed with water, dried over magnesium sulfate, filtered and evaporated. The residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 9:1) to give 0.27 g (60%) of the title compound as light brown solid. MS: 447.4 (MH+). | C#Cc1nc(-c2cccc(CCCCCC)c2)n(C)c1C(=O)N1CCC(N2CCCC2)CC1 | null | 60.5 | null |
488,541 | ord_dataset-37b0416f244344a08cf357e851eedf2a | null | 2001-01-01T00:01:00 | true | C([O:4][C:5]1[CH:6]=[CH:7][C:8]([O:11][CH3:12])=[N:9][CH:10]=1)(=O)C.[OH-].[Na+]>CO>[OH:4][C:5]1[CH:6]=[CH:7][C:8]([O:11][CH3:12])=[N:9][CH:10]=1 | COc1ccc(OC(C)=O)cn1 | 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 | 25 | 0.5 | To a solution of the 5acetoxy-2-methoxypyridine (600 mg, 3.59 mmol) in MeOH (10 mL) was added 1M aq. NaOH (10 mL, 10 mmol). After stirring at r.t. for 30 min, volatile solvent was removed in vacuo, acidified with HOAc and extracted with CHCl3(3×). The combind CHCl3 extracts were washed with H2O, dried (anhydrous MgSO4) and evaporated to give the title compound as a brown oil (240 mg, solidified on standing). | COc1ccc(O)cn1 | null | 53.4 | null |
749,232 | ord_dataset-844a22e1fcab44a5b59c5e2922b2855a | null | 2007-01-01T00:01:00 | true | [NH2:1][C:2]1[C:7]([C:8]([C:10]2[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:11]=2[O:17][CH3:18])=[O:9])=[CH:6][N:5]=[C:4](S(C)=O)[N:3]=1.[O:22]1[CH2:27][CH2:26][CH:25]([NH2:28])[CH2:24][CH2:23]1.O>CN1CCCC1=O>[NH2:1][C:2]1[C:7]([C:8]([C:10]2[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:11]=2[O:17][CH3:18])=[O:9])=[CH:6][N:5]=[C:4]([NH:28][CH:25]2[CH2:26][CH2:27][O:22][CH2:23][CH2:24]2)[N:3]=1 | NC1CCOCC1 | COc1ccc(F)cc1C(=O)c1cnc(S(C)=O)nc1N | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN1CCCC1=O | O | null | null | null | null | null | null | null | null | null | null | null | A solution of (4-amino-2-methanesulfinyl-pyrimidin-5-yl)-(5-fluoro-2-methoxy-phenyl)-methanone (235 mg, 0.73 mmol, Example 157) and tetrahydro-pyran-4-ylamine (Combi-Blocks) (260 mg, 2.3 mmol) in N-methylpyrrolidinone (15 ml) was heated for 30 minutes at 100° C. The solution was cooled, poured into water and extracted into ethyl acetate (2×). The combined organic extracts were washed with 5% sodium bicarbonate and saturated sodium chloride. The solution was dried (Na2SO4) and solvent was removed under vacuum to give a crude solid. Purification was by silica gel chromatography to give [4-amino-2-(tetrahydro-pyran-4-ylamino)-pyrimidin-5-yl]-(5-fluoro-2-methoxy-phenyl)-methanone as a white solid. HRMS, observed: 346.1445; Calcd for M+: 346.1441. | COc1ccc(F)cc1C(=O)c1cnc(NC2CCOCC2)nc1N | null | null | null |
1,246,768 | ord_dataset-c544c0c663f54dbea4ddb52ddde7934e | null | 2013-01-01T00:01:00 | true | [Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[C:4]([F:11])[CH:3]=1.[CH:12]1([C:15]2[CH:16]=[CH:17][C:18]([N:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)=[N:19][CH:20]=2)[CH2:14][CH2:13]1>>[Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([N:24]2[CH2:25][CH2:26][N:21]([C:18]3[CH:17]=[CH:16][C:15]([CH:12]4[CH2:14][CH2:13]4)=[CH:20][N:19]=3)[CH2:22][CH2:23]2)=[O:8])=[C:4]([F:11])[CH:3]=1 | c1cc(N2CCNCC2)ncc1C1CC1 | O=C(O)c1ccc(Br)cc1F | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | By reaction and treatment in the same manner as in Preparation Example 90 and using 4-bromo-2-fluorobenzoic acid (1.2 g) and 1-(5-cyclopropylpyridin-2-yl)piperazine (1.02 g) described in Preparation Example 187, the title compound (1.73 g) was obtained. | O=C(c1ccc(Br)cc1F)N1CCN(c2ccc(C3CC3)cn2)CC1 | null | 85.3 | null |
1,515,658 | ord_dataset-8c74302143c04eb9983e4b3a7ead2d72 | null | 2014-01-01T00:12:00 | true | [OH:1][CH2:2][C@@H:3]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH2:4][CH:5]([CH3:7])[CH3:6].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[CH3:6][CH:5]([CH3:7])[CH2:4][C@H:3]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH:2]=[O:1] | CC(C)C[C@@H](CO)NC(=O)OC(C)(C)C | 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 | 25 | 16 | To a solution of (S)-tert-butyl (1-hydroxy-4-methylpentan-2-yl)carbamate (2 g, 9.20 mmol) in DCM (30 mL) was added Dess-Martin Periodinane (5.86 g, 13.81 mmol) at 0° C. The reaction mixture was allowed to stir at RT for 16 h. The reaction mixture was quenched with NaHCO3, diluted with water and extracted in ethyl acetate. Organic layer was dried over Na2SO4 and concentrated which afforded (S)-tert-butyl (4-methyl-1-oxopentan-2-yl)carbamate as colorless oil (1.4 g, 6.50 mmol, 71% crude yield). The material was carried on without further purification. 1H NMR (300 MHz, DMSO-d6): δ 0.8-0.96 (m, 6H), 1.31-1.49 (m, 11H), 1.57-1.66 (m, 1H), 3.81-3.89 (m, 1H). 7.27 (d, 1H), 9.43 (s, 1H). | CC(C)C[C@@H](C=O)NC(=O)OC(C)(C)C | null | null | null |
799,113 | ord_dataset-56a22bc0c3b14f87b9aa3f2fc6488ee7 | null | 2007-01-01T00:12:00 | true | [NH2:1][C:2]1[CH:10]=[C:9]([C:11]2[C:16]([C:17]([F:20])([F:19])[F:18])=[CH:15][CH:14]=[CH:13][N:12]=2)[CH:8]=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].N1C=CC=CC=1.[C:27](Cl)(=[O:29])[CH3:28]>C1COCC1>[C:27]([NH:1][C:2]1[CH:10]=[C:9]([C:11]2[C:16]([C:17]([F:20])([F:18])[F:19])=[CH:15][CH:14]=[CH:13][N:12]=2)[CH:8]=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5])(=[O:29])[CH3:28] | NC(=O)c1ccc(-c2ncccc2C(F)(F)F)cc1N | CC(=O)Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | c1ccncc1 | C1CCOC1 | null | null | null | null | null | null | null | null | null | 25 | 0.17 | To a solution of 2-amino-4-(3-trifluoromethyl-pyridin-2-yl)-benzamide (0.5 mmol) and pyridine (0.55 mmol) in THF (5 ml) add acetyl chloride (0.55 mmol). Stir the mixture 10 minutes at room temperature. Concentrate under vacuum, extract with EtOAc, wash with brine, dry over Na2SO4, and concentrate under vacuum. Triturate with ether to give 2-acetylamino-4-(3-trifluoromethyl-pyridin-2-yl)-benzamide. | CC(=O)Nc1cc(-c2ncccc2C(F)(F)F)ccc1C(N)=O | null | null | null |
3,371 | ord_dataset-15ce1bcfb62046d9bec87d32620888d5 | null | 1976-01-01T00:03:00 | true | [S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[N:6]1[CH2:11][CH2:10][NH:9][CH2:8][CH2:7]1.C(N(CC)CC)C.[O:19]1[C:27]2[C:22](=[CH:23][C:24]([C:28](Cl)=[O:29])=[CH:25][CH:26]=2)[CH2:21][CH2:20]1>O1CCCC1>[O:19]1[C:27]2[C:22](=[CH:23][C:24]([C:28]([N:9]3[CH2:8][CH2:7][N:6]([C:2]4[S:1][CH:5]=[CH:4][N:3]=4)[CH2:11][CH2:10]3)=[O:29])=[CH:25][CH:26]=2)[CH2:21][CH2:20]1 | c1csc(N2CCNCC2)n1 | O=C(Cl)c1ccc2c(c1)CCO2 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(CC)CC | C1CCOC1 | null | null | null | null | null | null | null | null | null | 60 | null | To a solution of 9 g of 1-(2-thiazolyl) piperazine and 5 g of anhydrous triethylamine in 200 ml of anhydrous tetrahydroduran, there were added dropwise, a solution of 9.1 g of 5-coumaranyl carboxylic acid chloride in 20 ml of tetrahydrofuran. After the completion of the addition, the reaction mixture was heated at 60° C for two hours, then, the so-formed precipitate was suction-filtered off. The filtrate was evaporated under reduced pressure and the crystalline residue was washed with water then recrystallized in 70 ml of ethanol. There were obtained 12 g of 1-(5-coumaranyl carbonyl)-4-(2-thiazolyl) piperazine, melting (K) at 150°-151° C. | O=C(c1ccc2c(c1)CCO2)N1CCN(c2nccs2)CC1 | null | 76.3 | null |
290,889 | ord_dataset-5fb693db3950403e9ce1a516570153bf | null | 1994-01-01T00:05:00 | true | [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][CH2:9][CH2:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12].[C:18](OC(C)(C)C)(=[O:26])[C:19](OC(C)(C)C)=[O:20].CC(C)([O-])C.[K+].Cl>C1COCC1.O>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:19](=[O:20])[C:18]([OH:26])=[C:10]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:9]1 | CC(C)(C)OC(=O)CCNc1ccccc1F | CC(C)(C)OC(=O)C(=O)OC(C)(C)C | null | CC(C)(C)[O-] | Cl | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | O | null | null | null | null | null | null | null | null | null | 25 | 84 | To a solution of the title compound of Example C (5.41 g, 22.6 mmol) in dry THF (100 ml) was added di-tert-butyl oxalate (4.57 g, 22.6 mmol), followed by potassium tert-butoxide (5.07 g, 45.2 mmol) and the resulting dark yellow solution was stirred for 84 h at room temperature. The reaction mixture was then acidified with 1N HCl to pH=3, followed by the addition of H2O (35 ml) and the mixture was then extracted with CH2Cl2. The combined organic layers were dried with MgSO4, filtered and dried to give a solid which was chromatographed on silica gel eluting with 1/1/98 MeOH/HOAc/CH2Cl2 to give the title compound (3.166 g, 48%). Anal calcd for C15H16NO4F: C, 61.43; H, 5.50; N, 4.78. Found: C, 61.16; H, 5.50; N, 4.77. | CC(C)(C)OC(=O)C1=C(O)C(=O)N(c2ccccc2F)C1 | null | 47.8 | null |
971,370 | ord_dataset-03ba810b7f464a06b5d8787af2e8b64e | null | 2010-01-01T00:06:00 | true | [Cl:1][C:2]1[C:10]2[O:9][CH2:8][O:7][C:6]=2[CH:5]=[CH:4][C:3]=1[NH:11]C(=O)OC(C)(C)C.Cl.O1CCOCC1>>[Cl:1][C:2]1[C:10]2[O:9][CH2:8][O:7][C:6]=2[CH:5]=[CH:4][C:3]=1[NH2:11] | CC(C)(C)OC(=O)Nc1ccc2c(c1Cl)OCO2 | 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 | 5.5 | To a vial containing tert-butyl 4-chlorobenzo[d][1,3]dioxol-5-ylcarbamate (307.2 mg, 1.1 mmol, 1 equiv.) was added 5.5 mL of 4N HCl in dioxane (22 mmol, 20 equiv.). The mixture was stirred at room temperature for 5.5 h, the solvent removed under vacuum, the residue dissolved in ethyl acetate, washed with saturated NaHCO3, and brine. The combined organic layers was dried over anhydrous Na2SO4, filtered and the solvent removed under to give a quantitative yield 4-chlorobenzo[d][1,3]dioxol-5-amine. | Nc1ccc2c(c1Cl)OCO2 | null | null | null |
234,372 | ord_dataset-45d20d09e4d64f45bdd419044025b4d3 | null | 1991-01-01T00:09:00 | true | [C:1]1([C@@H:7]2[CH2:9][C@H:8]2[NH2:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[NH2:12][C:13]1[N:21]=[C:20]2[C:16]([N:17]=[CH:18][N:19]2[C@@H:22]2[CH2:26][C@H:25]([CH2:27][OH:28])[CH:24]=[CH:23]2)=[C:15](Cl)[N:14]=1.[OH-].[Na+]>CO>[NH2:12][C:13]1[N:21]=[C:20]2[C:16]([N:17]=[CH:18][N:19]2[C@@H:22]2[CH2:26][C@H:25]([CH2:27][OH:28])[CH:24]=[CH:23]2)=[C:15]([NH:10][C@@H:8]2[CH2:9][C@H:7]2[C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[N:14]=1 | Nc1nc(Cl)c2ncn([C@H]3C=C[C@@H](CO)C3)c2n1 | N[C@@H]1C[C@H]1c1ccccc1 | null | Cl | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | null | null | A solution of trans-2-phenyl cyclopropylamine.HCl (1.02 g, 6 mmol) in methanol (10 ml) was stirred with basic ion exchange resin for 5 minutes. The resin was filtered off and the filtrate was concentrated to a colorless oil. To this was added (±)-(cis)-4-(2-amino-6-chloro-9H-purin-9-yl)-2-cyclopentene-1-methanol (0.549 g, 2 mmol). The resulting solution was stirred in a Parr bomb at 80° C. for 12 hours 1 N NaOH 12 ml) was added and the solvent evaporated. The residual oil was chromatographed on silica gel. Title compound was eluted with 5% methanol-chloroform to give tan crystals after crystallization from acetonitrile-methanol (0.221 g, 30%), m.p.=188-190° C. | Nc1nc(N[C@@H]2C[C@H]2c2ccccc2)c2ncn([C@H]3C=C[C@@H](CO)C3)c2n1 | null | null | null |
619,275 | ord_dataset-2952e63264f5422a84e12cca1e0541ee | null | 2003-01-01T00:12:00 | true | [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[N:10]3[CH2:11][C:12]4[C:17]([C:9]3=[C:8]([CH:18]=O)[C:7]=2[N:20]=1)=[CH:16][CH:15]=[CH:14][CH:13]=4.[H-].[Na+].C(OP([CH2:31][CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])(OCC)=O)C>C1COCC1>[CH2:36]([O:35][C:33](=[O:34])[CH2:32][CH:31]=[CH:18][C:8]1[C:7]2[N:20]=[C:3]([O:2][CH3:1])[CH:4]=[CH:5][C:6]=2[N:10]2[CH2:11][C:12]3[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:9]=12)[CH3:37] | COc1ccc2c(n1)c(C=O)c1n2Cc2ccccc2-1 | CCOC(=O)CCP(=O)(OCC)OCC | 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 | null | 10.7 mmol of the compound obtained in Step E of Preparation 1 in 20 ml of anhydrous THF are placed in the presence of 1.2 eq of NaH (60% in oil) in 25 ml of anhydrous THF and of 1.2 eq of ethyl 3-(diethoxyphosphoryl)propanoate. The title compound is obtained after 3 hours' stirring at room temperature and gentle refluxing overnight. | CCOC(=O)CC=Cc1c2n(c3ccc(OC)nc13)Cc1ccccc1-2 | null | null | null |
586,228 | ord_dataset-cb5dd7a8b94e4f19a9148a1904b0dcb6 | null | 2003-01-01T00:03:00 | true | [CH3:1][O:2][C:3]1[C:10]([O:11][CH3:12])=[C:9]([O:13][CH3:14])[CH:8]=[CH:7][C:4]=1[CH:5]=O.[CH3:15][O:16][C:17]1[CH:18]=[C:19]([CH2:25][C:26]#[N:27])[CH:20]=[CH:21][C:22]=1[O:23][CH3:24]>>[CH3:15][O:16][C:17]1[CH:18]=[C:19]([C:25](=[CH:5][C:4]2[CH:7]=[CH:8][C:9]([O:13][CH3:14])=[C:10]([O:11][CH3:12])[C:3]=2[O:2][CH3:1])[C:26]#[N:27])[CH:20]=[CH:21][C:22]=1[O:23][CH3:24] | COc1ccc(CC#N)cc1OC | COc1ccc(C=O)c(OC)c1OC | null | null | null | null | null | null | null | 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 A, the reaction was performed with 1.96 g of 2,3,4-trimethoxybenzaldehyde (10 mmol) and 1.77 g 3,4-dimethoxyphenyl-acetonitrile (10 mmol), affording 2-(3,4-dimethoxy-phenyl)-3-(2,3,4-trimethoxy-phenyl)-acrylonitrile as yellow powder (yield 3.2 g, 90%). | COc1ccc(C(C#N)=Cc2ccc(OC)c(OC)c2OC)cc1OC | null | 90 | null |
236,800 | ord_dataset-56e7a343b17a4d6da818127ceb19589d | null | 1991-01-01T00:11:00 | true | [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9](=[CH2:13])[C:10]([OH:12])=[O:11])=[CH:5][CH:4]=1.[NH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[SH:21]>C(O)C>[NH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[S:21][CH2:13][CH:9]([C:6]1[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=1)[C:10]([OH:12])=[O:11] | Nc1ccccc1S | C=C(C(=O)O)c1ccc(OC)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 | null | null | A solution of 125 ml of ethanol, 8.9 g of 4-methoxy-α-methylene benzeneacetic acid and 5.35 ml of 2-amino thiophenol was refluxed for 7 hours. The ethanol was evaporated off and the residue was crystallized from 500 ml of isopropyl ether to obtain 11 g of the desired product melting at 118° C. and used as is for the following step. | COc1ccc(C(CSc2ccccc2N)C(=O)O)cc1 | null | null | null |
533,752 | ord_dataset-b1a34bc8c1204d51a772ed27396c794e | null | 2002-01-01T00:02:00 | true | [Cl:1][C:2]1[CH:18]=[C:17]([Cl:19])[CH:16]=[CH:15][C:3]=1[CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[N:7]=[C:6]1[CH3:14].[Cl:20][S:21](O)(=[O:23])=[O:22]>>[Cl:20][S:21]([C:11]1[CH:12]=[CH:13][C:8]2[N:7]=[C:6]([CH3:14])[N:5]([CH2:4][C:3]3[CH:15]=[CH:16][C:17]([Cl:19])=[CH:18][C:2]=3[Cl:1])[C:9]=2[CH:10]=1)(=[O:23])=[O:22] | O=S(=O)(O)Cl | Cc1nc2ccccc2n1Cc1ccc(Cl)cc1Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | 80 | 1.5 | In an ice bath, 1-(2,4-dichlorobenzyl)-2-methylbenzimidazole (4.00 g) is added to chlorosulfonic acid (20 ml) and the solution is stirred for 24 hours at room temperature and at 1.5 hours at 80° C. The reaction solution is poured into ice water, precipitated gummy solids are separated through filtration, and thus, a mixture of 5-chlorosulfonyl-1-(2,4-dichlorobenzyl)-2-methylbenzimidazole and 6-chlorosulfonyl-1-(2,4-dichlorobenzyl)-2-methylbenzimidazole is obtained. This material is immediately used for the following reaction. | Cc1nc2ccc(S(=O)(=O)Cl)cc2n1Cc1ccc(Cl)cc1Cl | null | null | null |
1,560,993 | ord_dataset-4e54080057a44c3887653391e24c90b6 | null | 2015-01-01T00:03:00 | true | C(O)(C(F)(F)F)=O.[CH:8]1([N:13]2[C:17]3[N:18]=[C:19]([NH2:22])[N:20]=[CH:21][C:16]=3[C:15]3[CH:23]=[CH:24][N:25]=[CH:26][C:14]2=3)[CH2:12][CH2:11][CH2:10][CH2:9]1.Cl[C:28]1[N:33]=[CH:32][C:31]([S:34]([N:37]2[CH2:42][CH2:41][N:40](C(OC(C)(C)C)=O)[CH2:39][CH2:38]2)(=[O:36])=[O:35])=[CH:30][CH:29]=1>>[CH:8]1([N:13]2[C:17]3[N:18]=[C:19]([NH:22][C:28]4[CH:29]=[CH:30][C:31]([S:34]([N:37]5[CH2:38][CH2:39][NH:40][CH2:41][CH2:42]5)(=[O:36])=[O:35])=[CH:32][N:33]=4)[N:20]=[CH:21][C:16]=3[C:15]3[CH:23]=[CH:24][N:25]=[CH:26][C:14]2=3)[CH2:9][CH2:10][CH2:11][CH2:12]1 | CC(C)(C)OC(=O)N1CCN(S(=O)(=O)c2ccc(Cl)nc2)CC1 | Nc1ncc2c3ccncc3n(C3CCCC3)c2n1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O=C(O)C(F)(F)F | null | null | null | null | null | null | null | null | null | null | null | null | Compound 359 was prepared as a white solid (TFA salt) from compound 4 and compound 360 using chemistry similar to that described in example 200. 1H NMR (500 MHz, CD3OD) δ ppm 9.59 (1 H, s), 9.29 (1 H, s), 8.72-8.78 (2 H, m), 8.63-8.66 (1 H, m), 8.61 (1 H, d), 8.22 (1 H, dd, J=8.8, 2.4 Hz), 5.51 (1 H, quin, J=8.9 Hz), 3.37 (8 H, s), 2.46-2.60 (2 H, m), 2.13-2.34 (4 H, m), 1.87-2.01 (2 H, m). LCMS-ESI (POS), M/Z, M+1. Found 478.9. | O=S(=O)(c1ccc(Nc2ncc3c4ccncc4n(C4CCCC4)c3n2)nc1)N1CCNCC1 | null | null | null |
1,126,408 | ord_dataset-285df12e34cd46e993e3c8ebc3a8962a | null | 2012-01-01T00:01:00 | true | [CH3:1][CH:2]1[CH2:7][NH:6][CH2:5][CH:4]([CH3:8])[N:3]1[C:9]1[S:10][C:11]2[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:14][C:12]=2[N:13]=1.Br[CH2:23][CH2:24][O:25][Si](C(C)(C)C)(C)C.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[CH3:8][CH:4]1[N:3]([C:9]2[S:10][C:11]3[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:14][C:12]=3[N:13]=2)[CH:2]([CH3:1])[CH2:7][N:6]([CH2:23][CH2:24][OH:25])[CH2:5]1 | CC(C)(C)[Si](C)(C)OCCBr | CC1CNCC(C)N1c1nc2ccc(C(F)(F)F)cc2s1 | null | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | O | null | null | null | null | null | null | null | null | null | 60 | 20 | A mixture of 2-(2,6-dimethyl piperazine-1-yl)-6-trifluoromethyl benzothiazole (360 mg), (2-bromoethoxy)-t-butyldimethyl silane (257 uL), potassium carbonate (157 mg) and dimethylformamide (2 mL) was stirred at 60° C. for 20 hours. To the reaction solution was added water and extracted with ethyl acetate. The organic layer was washed with water and dried over sodium carbonate. After evaporating the solvent, the residue was purified by column chromatograph on silica gel to give the title compound (265 mg). Yield: 65%. | CC1CN(CCO)CC(C)N1c1nc2ccc(C(F)(F)F)cc2s1 | null | 65 | null |
1,265,112 | ord_dataset-d3580a12b15e46cc91aa73f4f1a4a8cc | null | 2013-01-01T00:03:00 | true | Cl[C:2]1[N:7]=[C:6]([O:8][CH:9]([CH3:11])[CH3:10])[N:5]=[C:4]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH:23]=[C:22]([CH3:24])[N:21]=[CH:20]3)=[C:15]([O:25][CH3:26])[CH:14]=2)[N:3]=1.[OH:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[C:34]([F:37])([F:36])[F:35]>C(OCC)(=O)C>[CH:9]([O:8][C:6]1[N:7]=[C:2]([O:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[C:34]([F:35])([F:36])[F:37])[N:3]=[C:4]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH:23]=[C:22]([CH3:24])[N:21]=[CH:20]3)=[C:15]([O:25][CH3:26])[CH:14]=2)[N:5]=1)([CH3:11])[CH3:10] | Oc1ccccc1C(F)(F)F | COc1cc(Nc2nc(Cl)nc(OC(C)C)n2)ccc1-n1cnc(C)c1 | null | null | 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 | This compound was prepared from (4-chloro-6-isopropoxy-[1,3,5]triazin-2-yl)-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-amine and 2-hydroxy benzotrifluoride in analogy to example 3. Chromatography on silica gel using ethyl acetate as an eluent gave the title compound as a colorless solid in 99% yield. | COc1cc(Nc2nc(Oc3ccccc3C(F)(F)F)nc(OC(C)C)n2)ccc1-n1cnc(C)c1 | null | 99 | null |
570,183 | ord_dataset-5e1b2445a3d94ea592ddf2c284118a1e | null | 2002-01-01T00:11:00 | true | [CH:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]2[C:14]3[C:15]([CH3:22])=[C:16]([NH2:21])[C:17]([CH3:20])=[C:18]([CH3:19])[C:13]=3[O:12][C:11]2([CH3:24])[CH3:23])=[CH:6][CH:5]=1)([CH3:3])[CH3:2].[Cl:25][C:26]1[CH:34]=[CH:33][C:29]([C:30](Cl)=[O:31])=[CH:28][CH:27]=1>C(OCC)(=O)C.CCCCCC>[Cl:25][C:26]1[CH:34]=[CH:33][C:29]([C:30]([NH:21][C:16]2[C:17]([CH3:20])=[C:18]([CH3:19])[C:13]3[O:12][C:11]([CH3:24])([CH3:23])[CH:10]([C:7]4[CH:8]=[CH:9][C:4]([CH:1]([CH3:3])[CH3:2])=[CH:5][CH:6]=4)[C:14]=3[C:15]=2[CH3:22])=[O:31])=[CH:28][CH:27]=1 | Cc1c(C)c2c(c(C)c1N)C(c1ccc(C(C)C)cc1)C(C)(C)O2 | O=C(Cl)c1ccc(Cl)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOC(C)=O | CCCCCC | null | null | null | null | null | null | null | null | null | null | null | By using 3-(4-isopropylphenyl)-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-amine and 4-chlorobenzoyl chloride, the title compound was synthesized according to Example 1b. Yield: 71%. Melting point: 201-203° C. (Ethyl acetate-hexane) | Cc1c(C)c2c(c(C)c1NC(=O)c1ccc(Cl)cc1)C(c1ccc(C(C)C)cc1)C(C)(C)O2 | null | 71 | null |
1,473,099 | ord_dataset-fd1fa959d6264608b0b7fcda16741bfd | null | 2014-01-01T00:08:00 | true | Cl.[CH:2]1([CH2:5][O:6][C:7]2[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][C:8]=2[C:15]2[CH:20]=[CH:19][N:18]=[C:17]3[C:21]([C:25]([NH:27][CH:28]4[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]4)=[O:26])=[C:22]([CH3:24])[NH:23][C:16]=23)[CH2:4][CH2:3]1.C([O:37][C@@H:38]([CH3:42])[C:39](Cl)=[O:40])(=O)C>>[CH:2]1([CH2:5][O:6][C:7]2[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][C:8]=2[C:15]2[CH:20]=[CH:19][N:18]=[C:17]3[C:21]([C:25]([NH:27][CH:28]4[CH2:29][CH2:30][N:31]([C:39](=[O:40])[C@@H:38]([OH:37])[CH3:42])[CH2:32][CH2:33]4)=[O:26])=[C:22]([CH3:24])[NH:23][C:16]=23)[CH2:4][CH2:3]1 | COc1ccc(OCC2CC2)c(-c2ccnc3c(C(=O)NC4CCNCC4)c(C)[nH]c23)c1 | CC(=O)O[C@@H](C)C(=O)Cl | 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 | Starting from 7-[2-(cyclopropylmethoxy)-5-methoxyphenyl]-2-methyl-N-(piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide hydrochloride (example D.f14) and commercially available (2S)-1-chloro-1-oxopropan-2-yl acetate the title compound is obtained as colorless solid. | COc1ccc(OCC2CC2)c(-c2ccnc3c(C(=O)NC4CCN(C(=O)[C@H](C)O)CC4)c(C)[nH]c23)c1 | null | null | null |
1,409,072 | ord_dataset-7456bda2326f4bebaa874a5474d4cc0d | null | 2014-01-01T00:03:00 | true | [CH:1]([N:4]1[C:8]([C:9]2[S:10][C:11]3[CH2:12][CH2:13][O:14][C:15]4[CH:22]=[C:21](Br)[CH:20]=[CH:19][C:16]=4[C:17]=3[N:18]=2)=[N:7][CH:6]=[N:5]1)([CH3:3])[CH3:2].[F:24][C:25]1[C:30](B(O)O)=[CH:29][CH:28]=[CH:27][N:26]=1>>[F:24][C:25]1[C:30]([C:21]2[CH:20]=[CH:19][C:16]3[C:17]4[N:18]=[C:9]([C:8]5[N:4]([CH:1]([CH3:3])[CH3:2])[N:5]=[CH:6][N:7]=5)[S:10][C:11]=4[CH2:12][CH2:13][O:14][C:15]=3[CH:22]=2)=[CH:29][CH:28]=[CH:27][N:26]=1 | CC(C)n1ncnc1-c1nc2c(s1)CCOc1cc(Br)ccc1-2 | OB(O)c1cccnc1F | null | null | null | null | null | null | null | 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 128, 2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-8-bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene and 2-fluoropyridin-3-ylboronic acid were reacted to give 487 (0.226 g, 20%). 1H NMR (400 MHz, DMSO) δ 8.48 (d, J=8.3, 1H), 8.33-8.18 (m, 2H), 8.12 (s, 1H), 7.54-7.45 (m, 2H), 7.37 (d, J=1.5, 1H), 5.96-5.75 (m, 1H), 4.44 (t, J=5.0, 2H), 3.49 (t, J=5.0, 2H), 1.90-1.28 (m, 6H). MS (ESI(+)): m/z 408.12 (M+H) | CC(C)n1ncnc1-c1nc2c(s1)CCOc1cc(-c3cccnc3F)ccc1-2 | null | 20 | null |
1,083,416 | ord_dataset-afd812677c134591a99f46ce28de2524 | null | 2011-01-01T00:08:00 | true | [CH:1]1([N:6]2[CH2:12][C:11]([F:14])([F:13])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][C:23]=4[O:31][CH3:32])=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(C(C)C)C(C)C)C.[NH2:42][CH:43]1[CH2:48][CH2:47][N:46]([C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[CH2:45][CH2:44]1>CN(C)C=O>[C:52]([O:51][C:49]([N:46]1[CH2:45][CH2:44][CH:43]([NH:42][C:26](=[O:27])[C:25]2[CH:29]=[CH:30][C:22]([NH:21][C:19]3[N:18]=[CH:17][C:8]4[N:9]([CH3:16])[C:10](=[O:15])[C:11]([F:13])([F:14])[CH2:12][N:6]([CH:1]5[CH2:5][CH2:4][CH2:3][CH2:2]5)[C:7]=4[N:20]=3)=[C:23]([O:31][CH3:32])[CH:24]=2)[CH2:48][CH2:47]1)=[O:50])([CH3:55])([CH3:54])[CH3:53] | COc1cc(C(=O)O)ccc1Nc1ncc2c(n1)N(C1CCCC1)CC(F)(F)C(=O)N2C | CC(C)(C)OC(=O)N1CCC(N)CC1 | 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 | CN(C)C=O | null | null | null | null | null | null | null | null | null | 25 | 1 | To a mixture of 0.25 g (0.56 mmole) of 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoic acid (I-22), 0.30 mL (1.7 mmole) of ethyldiisopropyl amine and 0.12 g (0.62 mmole) of 4-amino-1-Boc-piperidine in 4.0 mL of dimethylformamide was added 0.27 g (0.62 mmole) of 1-(di-1-pyrrolidinylmethylene)-1H-benzotriazolium 3-oxide hexafluorophosphate. The mixture was stirred at room temperature for 1 hour, then diluted with 10 mL of ice water. The resulting solid was collected by filtration, washed with saturated sodium carbonate and water, and dried under vacuum. Purification by silica gel chromatography, eluting with hexane-ethylacetate (gradient, 70:30-0:100) gave 0.21 g of 4-[4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoylamino]-piperidine-1-carboxylic acid tert-butyl ester (I-71) as a white solid. | COc1cc(C(=O)NC2CCN(C(=O)OC(C)(C)C)CC2)ccc1Nc1ncc2c(n1)N(C1CCCC1)CC(F)(F)C(=O)N2C | null | 59.6 | null |
1,250,773 | ord_dataset-c544c0c663f54dbea4ddb52ddde7934e | null | 2013-01-01T00:01:00 | true | [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][C@H:11]([NH:18]C(=O)OCC2C=CC=CC=2)[C:12]2[O:13][C:14](=[O:17])[NH:15][N:16]=2)=[CH:2]1>O1CCCC1.[Pd]>[NH2:18][C@H:11]([C:12]1[O:13][C:14](=[O:17])[NH:15][N:16]=1)[CH2:10][C:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[NH:1][CH:2]=1 | O=C(N[C@@H](Cc1c[nH]c2ccccc12)c1n[nH]c(=O)o1)OCc1ccccc1 | null | null | [Pd] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | null | 24 | A solution of (S)-benzyl 2-(1H-indol-3-yl)-1-(5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)ethyl-carbamate (1.41 g, 3.73 mmol) in anhydrous tetrahydrofuran (100 mL) was mixed with 10% palladium on activated carbon (160 mg) and hydrogenated for 24 h at room temperature and at 3 bar. A further portion of 20% palladium on activated carbon (160 mg) was added and the mixture hydrogenated for a further 24 h at 3 bar and 40° C. The catalyst was then filtered off, the filtrate concentrated to low volume in a vacuum and the residue (1.24 g) purified by flash chromatography (100 g, 20×4.0 cm) with chloroform/methanol (95:5). | N[C@@H](Cc1c[nH]c2ccccc12)c1n[nH]c(=O)o1 | null | null | null |
335,847 | ord_dataset-65c44df6676d4ce3a1874db5d7958ca9 | null | 1996-01-01T00:08:00 | true | [NH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[F:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][P:15]([O-:24])[O:16][C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)=[CH:10][CH:9]=1.[ClH:25]>C(Cl)Cl.CCOCC>[ClH:25].[NH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[P:15]([O:16][C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=1)(=[O:24])[O:14][C:11]1[CH:10]=[CH:9][C:8]([F:7])=[CH:13][CH:12]=1 | [O-]P(Oc1ccc(F)cc1)Oc1ccc(F)cc1 | C1CCNCC1 | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOCC | ClCCl | null | null | null | null | null | null | null | null | null | null | null | A mixture of piperidine trimer (4.5 g, 54 mmole) and di(4-fluorophenyl)phosphite (14.8 g, 55 mmole) was heated at 90°-100° C. for 3 h under nitrogen. The resulted oil was cooled and dissolved in a mixture of 50 mL CH2Cl2 and 50 mL ether. The solution was saturated with dry HCl, the oil was separated and solidified after several hours. The solid was filtered, washed with ether and dried. The hygroscopic material was stirred in 200 mL dry ether for several hours and the yellowish solid was filtered and dried. The product was obtained in 54% yield (11.6 g) and used for subsequent reaction: mp. 155°-165° C. (dec); 1H NMR (D2O) δ7.2-6.8 (m, 8H), 3.6-2.9 (m, 3H), 2.2-1.4 (m, 6H); MS (FAB) m/e 354 (M-Cl)+. Anal. (exact mass, HRMS) calcd. for C17H19N1O3P1Cl2 m/e 354.1070, found 354.1098. | O=P(Oc1ccc(F)cc1)(Oc1ccc(F)cc1)C1CCCCN1 | null | 54 | null |
931,885 | ord_dataset-d8a5dc784dde4465894ec7c69d2e3ba6 | null | 2010-01-01T00:01:00 | true | [O:1]=[S:2]1(=[O:17])[CH2:7][CH2:6][N:5]([C:8]2[C:14]([F:15])=[CH:13][C:11]([NH2:12])=[CH:10][C:9]=2[F:16])[CH2:4][CH2:3]1.[O-]S(C(F)(F)F)(=O)=O.[Li+].[O:27]1[CH2:33][C@@H:28]1[C:29]([O:31][CH3:32])=[O:30]>C(#N)C>[O:17]=[S:2]1(=[O:1])[CH2:7][CH2:6][N:5]([C:8]2[C:14]([F:15])=[CH:13][C:11]([NH:12][CH2:33][C@@H:28]([OH:27])[C:29]([O:31][CH3:32])=[O:30])=[CH:10][C:9]=2[F:16])[CH2:4][CH2:3]1 | Nc1cc(F)c(N2CCS(=O)(=O)CC2)c(F)c1 | COC(=O)[C@H]1CO1 | null | O=S(=O)([O-])C(F)(F)F | [Li+] | 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 | 70 | 7 | A solution of 4-(1,1-dioxidothiomorpholin-4-yl)-3,5-difluoroaniline (EXAMPLE 15, Step 3, 1.30 g, 5.0 mmol) in acetonitrile (7.5 mL) is treated with lithium triflate (0.60 g, 5.0 mmol) and methyl (2R)-2,3-epoxypropanoate (0.51 g, 0.46 mL, 5.0 mmol) and heated to 70° C. for 2 h. At this time an additional amount (1.5 mmol each) of the two reagents is added and the mixture stirred for another 7 h at 70° C. The reaction mixture is then cooled to room temperature, concentrated, and purified by column chromatography (50→60% ethyl acetate-hexane) to provide the title compound (1.03 g, 57%), MS (m/z): [M+H]+=365; 1H NMR (300 MHz, CDCl3): δ 3.04 (d, 1H), 3.15 (m, 4H), 3.31-3.46 (m, 2H), 3.47-3.56 (m, 4H), 3.83 (s, 3H), 4.20 (t, 1H), 4.40 (m, 1H), 6.17 (d, 2H). | COC(=O)[C@H](O)CNc1cc(F)c(N2CCS(=O)(=O)CC2)c(F)c1 | null | 56.5 | null |
1,019,949 | ord_dataset-f024e9664ab64906a71a2ff6004cb3d0 | null | 2010-01-01T00:12:00 | true | C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.[OH:34][CH2:35][C@@H:36]1[CH2:40][CH2:39][CH2:38][N:37]1[C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42].[S:48]1[CH:52]=[CH:51][C:50]2[CH:53]=[C:54](O)[CH:55]=[CH:56][C:49]1=2.C(N(CC)CC)C>ClCCl>[S:48]1[CH:52]=[CH:51][C:50]2[CH:53]=[C:54]([O:34][CH2:35][C@@H:36]3[CH2:40][CH2:39][CH2:38][N:37]3[C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH:55]=[CH:56][C:49]1=2 | Oc1ccc2sccc2c1 | CC(C)(C)OC(=O)N1CCC[C@H]1CO | null | CC(C)OC(=O)/N=N/C(=O)OC(C)C | c1ccc(P(c2ccccc2)c2ccccc2)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | CCN(CC)CC | null | null | null | null | null | null | null | null | null | 25 | 8 | Polystyrene supported triphenylphosphine (2.9 mmol/g, 1.70 g, 4.95 mmol) was treated with diisopropylazodicarboxylate (0.779 mL, 3.96 mmol) at 0° C. in anhydrous dichloromethane. A mixture of (S)-tert-butyl 2-(hydroxymethyl)pyrrolidine-1-carboxylate (0.5 g, 3.3 mmol), benzo[b]thiophen-5-ol (0.5 g, 3.3 mmol) and triethylamine (0.689 mL, 4.95 mmol) in dichloromethane (5 mL) was then added to the reaction. The mixture was then allowed to warm up to room temperature and stirred overnight. The reaction was then filtered off and the filtrate purified by column chromatography on silica gel using a gradient of 15 to 50% ethyl acetate in hexanes to obtain a clear oil that solidied into an off-white solid on standing. Yield=0.48 g. MS (M+H)+ 334. | CC(C)(C)OC(=O)N1CCC[C@H]1COc1ccc2sccc2c1 | null | null | null |
1,656,159 | ord_dataset-42cd9bc5aae3485f9a58f1527bd3abf0 | null | 2015-01-01T00:11:00 | true | [CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][C@H:3]1[C:7]1[N:11]2[CH:12]=[C:13]([O:16][C@H:17]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[C@@H:20]([NH2:27])[CH2:19][CH2:18]3)[CH:14]=[CH:15][C:10]2=[N:9][N:8]=1.ClC(Cl)(Cl)C[O:31][C:32](=O)[NH:33][C:34]1[N:35]([C:43]2[CH:48]=[CH:47][C:46]([O:49][Si:50]([CH:57]([CH3:59])[CH3:58])([CH:54]([CH3:56])[CH3:55])[CH:51]([CH3:53])[CH3:52])=[C:45]([Cl:60])[CH:44]=2)[N:36]=[C:37]([C:39]([CH3:42])([CH3:41])[CH3:40])[CH:38]=1.CCN(C(C)C)C(C)C>O1CCOCC1>[C:39]([C:37]1[CH:38]=[C:34]([NH:33][C:32]([NH:27][C@@H:20]2[C:21]3[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=3)[C@H:17]([O:16][C:13]3[CH:14]=[CH:15][C:10]4[N:11]([C:7]([C@@H:3]5[CH2:4][CH2:5][CH2:6][N:2]5[CH3:1])=[N:8][N:9]=4)[CH:12]=3)[CH2:18][CH2:19]2)=[O:31])[N:35]([C:43]2[CH:48]=[CH:47][C:46]([O:49][Si:50]([CH:54]([CH3:56])[CH3:55])([CH:57]([CH3:58])[CH3:59])[CH:51]([CH3:53])[CH3:52])=[C:45]([Cl:60])[CH:44]=2)[N:36]=1)([CH3:42])([CH3:41])[CH3:40] | CN1CCC[C@H]1c1nnc2ccc(O[C@@H]3CC[C@H](N)c4ccccc43)cn12 | CC(C)[Si](Oc1ccc(-n2nc(C(C)(C)C)cc2NC(=O)OCC(Cl)(Cl)Cl)cc1Cl)(C(C)C)C(C)C | 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 | C1COCCO1 | null | null | null | null | null | null | null | null | null | null | null | A mixture of Intermediate E (145 mg, 0.40 mmol) and [5-tert-butyl-2-(3-chloro-4-triisopropylsilanyloxy-phenyl)-2H-pyrazol-3-yl]-carbamic acid 2,2,2-trichloro-ethyl ester (WO2011/154734A1, which is incorporated herein by reference, 251 mg, 0.420 mmol) in 1,4-dioxane (4 mL) and DIPEA (110 μL, 0.63 mmol) was stirred at 90° C. for 5.5 h. The cooled mixture was concentrated in vacuo. The residue was purified by FCC, using 0-12% MeOH in DCM, to give the title compound (288 mg, 89%). LCMS (Method 3): Rt 3.85 min, m/z 811 [MH+]. | CC(C)[Si](Oc1ccc(-n2nc(C(C)(C)C)cc2NC(=O)N[C@H]2CC[C@@H](Oc3ccc4nnc([C@@H]5CCCN5C)n4c3)c3ccccc32)cc1Cl)(C(C)C)C(C)C | null | 89 | null |
125,924 | ord_dataset-fd44e5eeeeb4473cb5fbff2d885d7833 | null | 1985-01-01T00:01:00 | true | [Na].[Cl:2][C:3]1[C:12](Cl)=[N:11][C:10]2[C:5](=[CH:6][CH:7]=[C:8]([O:14][CH3:15])[CH:9]=2)[N:4]=1.[CH3:16][OH:17]>>[Cl:2][C:3]1[C:12]([O:17][CH3:16])=[N:11][C:10]2[C:5](=[CH:6][CH:7]=[C:8]([O:14][CH3:15])[CH:9]=2)[N:4]=1 | CO | COc1ccc2nc(Cl)c(Cl)nc2c1 | null | [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 | 50 | null | In a flame-dried reaction flask under a dry nitrogen atmosphere, there was slowly added a solution consisting of 850 mg. of sodium dissolved in 80 ml. of methanol to a slurry of 7.1 g. of 2,3-dichloro-6-methoxyquinoxaline in 60 ml. of methanol at 50° C. over a period of seven hours. The resulting mixture was then heated at 50° C. overnight and finally cooled to room temperature. Upon completion of this step, the spent reaction mixture was concentrated in vacuo and the residue subsequently dissolved in chloroform, followed by washing with water and drying over anhydrous magnesium sulfate. After removal of the drying agent by means of filtration and the solvent by means of evaporation under reduced pressure, the resulting residue was subsequently chromatographed on a column of 400 ml. of silica gel, followed by elution with toluene. The good fractions were combined and concentrated in vacuo to ultimately afford a white solid consisting of 6.1 g. (88%) of pure 2-chloro-3,6-methoxyquinoxaline. m.p. 79°-81° C. | COc1ccc2nc(Cl)c(OC)nc2c1 | null | null | null |
1,577,484 | ord_dataset-9741bb5fd93044078df2a45f45733054 | null | 2015-01-01T00:04:00 | true | [CH2:1]([C:3]1[CH:4]=[N:5][C:6]([N:9]2[CH2:14][CH2:13][CH:12]([C@H:15]3[CH2:17][C@H:16]3[CH2:18][CH2:19][O:20][C:21]3[CH:26]=[CH:25][C:24]([CH2:27][CH2:28][OH:29])=[C:23]([F:30])[CH:22]=3)[CH2:11][CH2:10]2)=[N:7][CH:8]=1)[CH3:2].N1(C(=O)CC2C(F)=C[C:40]([OH:44])=CC=2F)CCC1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>ClCCl>[CH2:1]([C:3]1[CH:4]=[N:5][C:6]([N:9]2[CH2:10][CH2:11][CH:12]([C@H:15]3[CH2:17][C@H:16]3[CH2:18][CH2:19][O:20][C:21]3[CH:26]=[CH:25][C:24]([CH2:27][C:28]([O:44][CH3:40])=[O:29])=[C:23]([F:30])[CH:22]=3)[CH2:13][CH2:14]2)=[N:7][CH:8]=1)[CH3:2] | CCc1cnc(N2CCC([C@H]3C[C@H]3CCOc3ccc(CCO)c(F)c3)CC2)nc1 | O=C(Cc1c(F)cc(O)cc1F)N1CCC1 | null | CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C | c1ccc(P(c2ccccc2)c2ccccc2)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | 25 | 3 | To a solution of 2-[4-(2-{(1S,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethoxy)-2-fluorophenyl]ethanol (0.200 g, 0.726 mmol) in 5 ml anhydrous dichloromethane at RT was added a solution of 1-(azetidin-1-yl)-2-(2,6-difluoro-4-hydroxyphenyl) ethanone (0.160 g, 0.871 mmol) in 5 ml anhydrous dichloromethane. Triphenylphosphine, polymer-bound (0.571 g, 1.90 mmol), and di-tert-butyl azodicarboxylate (0.334 g, 1.45 mmol) was added and the slurry stirred at RT for 3 hours. The mixture was filtered through Celite and the filtrate concentrated in vacuo. The residue was purified by column chromatography on silica gel (Biotage column, 50 g) using a gradient eluent of 0-50% ethyl acetate in hexanes (700 ml) to afford the title compound. LC/MS (m/z) 442.3 (M+H)+. | CCc1cnc(N2CCC([C@H]3C[C@H]3CCOc3ccc(CC(=O)OC)c(F)c3)CC2)nc1 | null | null | null |
894,065 | ord_dataset-11068b1e475b4c5b82e56726ab0dddb7 | null | 2009-01-01T00:07:00 | true | [Cl:1][C:2]1[N:10]=[CH:9][C:8]([Cl:11])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].S(Cl)(Cl)=O.[CH3:16]O>CCOCC>[Cl:1][C:2]1[N:10]=[CH:9][C:8]([Cl:11])=[CH:7][C:3]=1[C:4]([O:6][CH3:16])=[O:5] | O=C(O)c1cc(Cl)cnc1Cl | CO | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O=S(Cl)Cl | CCOCC | null | null | null | null | null | null | null | null | null | 0 | 1 | A solution of 2,5-dichloronicotinic acid (20.2 g, 0.105 mol, Aldrich) in methanol (500 mL) was cooled to 0° C. and neat thionyl chloride (38 mL, 63 g, 0.525 mol) was added over ˜30 min. The reaction mixture was stirred at 0° C. for 1 hour. The cooling bath was removed, the reaction temperature was allowed to warm to room temperature, and the reaction was allowed to stir for an additional 2 days at room temperature. The solvent was removed under reduced pressure to give an off-white residue. The residue was dissolved in ether (˜500 mL) and the resulting solution was washed successively with saturated aqueous sodium bicarbonate solution (˜300 mL), water (˜300 mL), and brine (˜300 mL). The organic layer was separated, dried over anhydrous magnesium sulfate, and filtered. Removal of the solvent under reduced pressure yielded methyl 2,5-dichloronicotinate (21.0 g, 97% yield) as a white solid. | COC(=O)c1cc(Cl)cnc1Cl | null | 97 | null |
191,102 | ord_dataset-d1bd8c96676b4d21aad27b173c6b4eff | null | 1989-01-01T00:06:00 | true | C([Li])CCC.[C:6]1([S:12]([CH3:15])(=[O:14])=[O:13])[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.C1(N(C2C=CC=CC=2)C([O:25][C:26](=O)[C:27]2[CH:32]=[CH:31][C:30]([CH2:33][N:34]3[C:42]4[C:37](=[CH:38][CH:39]=[C:40]([NH:43][C:44](=[O:52])[CH:45]([CH2:50][CH3:51])[CH2:46][CH2:47][CH2:48][CH3:49])[CH:41]=4)[CH:36]=[CH:35]3)=[C:29]([O:53][CH3:54])[CH:28]=2)=O)C=CC=CC=1.P([O-])(O)(O)=O.[K+]>O1CCCC1>[CH2:50]([CH:45]([CH2:46][CH2:47][CH2:48][CH3:49])[C:44]([NH:43][C:40]1[CH:41]=[C:42]2[C:37]([CH:36]=[CH:35][N:34]2[CH2:33][C:30]2[CH:31]=[CH:32][C:27]([C:26](=[O:25])[CH2:15][S:12]([C:6]3[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=3)(=[O:14])=[O:13])=[CH:28][C:29]=2[O:53][CH3:54])=[CH:38][CH:39]=1)=[O:52])[CH3:51] | CCCCC(CC)C(=O)Nc1ccc2ccn(Cc3ccc(C(=O)OC(=O)N(c4ccccc4)c4ccccc4)cc3OC)c2c1 | CS(=O)(=O)c1ccccc1 | null | O=P([O-])(O)O | [K+] | [Li]CCCC | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | 25 | 2 | A solution of butyllithium (0.86 ml of a 2.3M solution in hexanes) was added to a solution of methyl phenyl sulphone (312 mg) in dry tetrahydrofuran (THF) (5 ml.) at -78° C. After 15 minutes a white suspension formed. To this mixture was then added a solution of 4-[6-(2-ethylhexanamido)indole-1-yl-methyl]-3-methoxybenzoic N,N-diphenylcarbamic anhydride (A) (500 mg) in THF (4 ml). After two hours, the mixture was allowed to warm to ambient temperature and an excess of a saturated solution of potassium dihydrogen phosphate was added. The solvent was removed by evaporation and the residue was partitioned between water and ethyl acetate. The organic phase was dried (Na2SO4) and evaporated. The residual gum was purified by chromatography on silica gel (20 g), using 2:98 v/v ether:methylene chloride as eluent, to give the title compound as a white solid (200 mg, 44%); mp 131°-133° C. | CCCCC(CC)C(=O)Nc1ccc2ccn(Cc3ccc(C(=O)CS(=O)(=O)c4ccccc4)cc3OC)c2c1 | null | 44.1 | null |
1,750,733 | ord_dataset-97eb2ab57fec4160922caae33b54d956 | null | 2016-01-01T00:08:00 | true | [OH:1][CH2:2][C@H:3]1[CH2:7][CH2:6][CH2:5][N:4]1[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].C([O-])([O-])=O.[Cs+].[Cs+].Cl[C:22]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:25]=[C:24]([C:32]#[N:33])[N:23]=1>CN1C(=O)CCC1>[C:32]([C:24]1[N:23]=[C:22]([O:1][CH2:2][C@H:3]2[CH2:7][CH2:6][CH2:5][N:4]2[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C:31]2[C:26]([CH:25]=1)=[CH:27][CH:28]=[CH:29][CH:30]=2)#[N:33] | CC(C)(C)OC(=O)N1CCC[C@@H]1CO | N#Cc1cc2ccccc2c(Cl)n1 | null | O=C([O-])[O-] | [Cs+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN1CCCC1=O | null | null | null | null | null | null | null | null | null | null | 0 | 1 | A mixture of (R)-tert-butyl 2-(hydroxymethyl)pyrrolidine-1-carboxylate (444 mg, 2.206 mmol) and Cs2CO3 (719 mg, 2.206 mmol) in NMP (4 mL) were stirred at 0° C. for 1 hour. Next, 1-chloroisoquinoline-3-carbonitrile (400 mg, 2.121 mmol) was added and the reaction mixture was heated at 140° C. for 15 minutes in a microwave reactor. Additional Cs2CO3 (719 mg, 2.206 mmol) was added. The reaction mixture heated at 140° C. for 1 hour to give the title compound, which was used directly in the next step. | CC(C)(C)OC(=O)N1CCC[C@@H]1COc1nc(C#N)cc2ccccc12 | null | null | null |
844,113 | ord_dataset-e2b35e721c2741999b0005d12691f9fe | null | 2008-01-01T00:10:00 | true | [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2.[CH2:11]([CH:18]1[CH2:23][CH2:22][N:21]([C:24](=[O:28])[C:25](O)=[O:26])[CH2:20][CH2:19]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>CCCCCC>[CH2:11]([CH:18]1[CH2:19][CH2:20][N:21]([C:24](=[O:28])[C:25]([NH:1][C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[NH:7][CH:6]=[CH:5]3)=[O:26])[CH2:22][CH2:23]1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1 | Nc1ccc2[nH]ccc2c1 | O=C(O)C(=O)N1CCC(Cc2ccccc2)CC1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCCCCC | null | null | null | null | null | null | null | null | null | null | null | null | The title compound is prepared from 5-aminoindole (Aldrich) and (4-benzyl-piperidin-1-yl)-oxo-acetic acid (Example 5b) according to the method described in Example 1c. Melting Point: 68-72° C. (hexane) | O=C(Nc1ccc2[nH]ccc2c1)C(=O)N1CCC(Cc2ccccc2)CC1 | null | null | null |
908,531 | ord_dataset-46d216f2c4374ef5b9df90427e2a4cd4 | null | 2009-01-01T00:09:00 | true | [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.BrN1C(=[O:21])CCC1=O.C1N2CN3CN(C2)CN1C3>C(Cl)(Cl)(Cl)Cl.C(Cl)(Cl)Cl>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([CH:14]=[O:21])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1 | O=C1CCC(=O)N1Br | Cc1ccc(-c2ccc(C)cc2)cc1 | null | C1N2CN3CN1CN(C2)C3 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClC(Cl)Cl | ClC(Cl)(Cl)Cl | null | null | null | null | null | null | null | null | null | 120 | null | Into CCl4 solvent, 2.4 g(13.3 mmol) of the compound produced in Example 1 (Compound 1) and 0.536 g(3.0 mmol) of N-bromosuccinimide were added and refluxed for 24 hours. After cooled down, the reactant was suction-filtrated and the resultant solution was washed with distilled water and then was dried with anhydrous magnesium sulfate. The dried product was dissolved again in chloroform together with 5.34 g(51.2 mmol) of hexamethylenetetraamine and refluxed for 5 hours. After the reactant was cooled down, the solvent was distilled off under reduced pressure and the residue was refluxed severely in acetic acid/H2O(17 mL/17 mL) at 120° C. for 2 hours. Finally, 7 mL of HCl was added to be refluxed. After cooled down, the reactant was extracted with methylene chloride. The solution was distilled off under reduced pressure and the residue was purified through the column chromatography (silica gel, ethyl acetate/n-hexane=1:3) to be dried. Yield; 24%. | Cc1ccc(-c2ccc(C=O)cc2)cc1 | null | 24 | null |
853,867 | ord_dataset-faa0236be76c4501841c954527cd1b6c | null | 2008-01-01T00:12:00 | true | [NH2:1][C:2]1[C:3]([C:7]2[NH:23][C:10]3=[CH:11][C:12]4[C:13]([CH3:22])([CH3:21])[C:14](=[O:20])[N:15]([CH2:18][CH3:19])[C:16]=4[CH:17]=[C:9]3[N:8]=2)=[N:4][NH:5][CH:6]=1.[C:24](Cl)(=[O:29])[C:25]([CH3:28])([CH3:27])[CH3:26]>>[CH2:18]([N:15]1[C:16]2[CH:17]=[C:9]3[N:8]=[C:7]([C:3]4[C:2]([NH:1][C:24](=[O:29])[C:25]([CH3:28])([CH3:27])[CH3:26])=[CH:6][NH:5][N:4]=4)[NH:23][C:10]3=[CH:11][C:12]=2[C:13]([CH3:22])([CH3:21])[C:14]1=[O:20])[CH3:19] | CCN1C(=O)C(C)(C)c2cc3[nH]c(-c4n[nH]cc4N)nc3cc21 | CC(C)(C)C(=O)Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | N-[3-(5-Ethyl-7,7-dimethyl-6-oxo-1,5,6,7-tetrahydro-imidazo[4,5-f]indol-2-yl)-1H-pyrazol-4-yl]-2,2-dimethyl-propionamide was prepared using 2-(4-amino-1H-pyrazol-3-yl)-5-ethyl-7,7-dimethyl-5,7-dihydro-1H-imidazo[4,5-f]indol-6-one (250 mg, 0.81 mmol) and pivaloyl chloride (109 μl, 0.89 mmol). The title compound was obtained as brown powder (171 mg, 53%). | CCN1C(=O)C(C)(C)c2cc3[nH]c(-c4n[nH]cc4NC(=O)C(C)(C)C)nc3cc21 | null | null | null |
1,413,390 | ord_dataset-f8e6e6a2d2bf4135b9e346456c81700f | null | 2014-01-01T00:04:00 | true | Br[C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[F:9].[CH2:10]([S:12][C:13]1[CH:14]=[C:15](B(O)O)[CH:16]=[CH:17][CH:18]=1)[CH3:11]>>[CH2:10]([S:12][C:13]1[CH:18]=[C:17]([C:2]2[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=2[F:9])[CH:16]=[CH:15][CH:14]=1)[CH3:11] | CCSc1cccc(B(O)O)c1 | Nc1ccc(Br)c(F)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The title compound (430 mg) was prepared from 4-bromo-3-fluoroaniline (300 mg, 1.6 mmol) and 3-(ethylthio)phenylboronic acid (370 mg, 2.0 mmol) as a yellow liquid. | CCSc1cccc(-c2ccc(N)cc2F)c1 | null | 108.7 | null |
349,726 | ord_dataset-66f304805e5d47fc8d3c722b1bd8dfa2 | null | 1996-01-01T00:12:00 | true | [CH2:1]([N:3]1[C:12](=[O:13])[C:11]2[N:10]([CH3:14])[C:9](/[CH:15]=[CH:16]/[C:17]3[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=3)=[N:8][C:7]=2[N:6]([CH2:24][CH3:25])[C:4]1=[O:5])[CH3:2].C(=O)([O-])[O-].[K+].[K+].Cl[CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35].O>CN(C)C=O>[CH2:37]([O:36][C:34]([CH2:33][O:23][C:20]1[CH:19]=[CH:18][C:17](/[CH:16]=[CH:15]/[C:9]2[N:10]([CH3:14])[C:11]3[C:12](=[O:13])[N:3]([CH2:1][CH3:2])[C:4](=[O:5])[N:6]([CH2:24][CH3:25])[C:7]=3[N:8]=2)=[CH:22][CH:21]=1)=[O:35])[CH3:38] | CCOC(=O)CCl | CCn1c(=O)c2c(nc(/C=C/c3ccc(O)cc3)n2C)n(CC)c1=O | null | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CN(C)C=O | null | null | null | null | null | null | null | null | null | 25 | 2 | Compound 175 (300 mg, 0.88 mmol) obtained in Reference Example 114 was dissolved in 10 ml of dimethyl formamide. To the solution were added 731 mg (5.29 mmol) of potassium carbonate and 0.47 ml (4.41 mmol) of ethyl chloroacetate, and the mixture was stirred at room temperature for 2 hours. Water was added thereto to dissolve potassium carbonate and the deposited crystals were collected by filtration. The collected crude crystals were dissolved in chloroform, washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, followed by evaporation under reduced pressure. The residue was recrystallized from hexane/ethyl acetate to give 341 mg (yield 91%) of Compound 180 as pale yellow needles. | CCOC(=O)COc1ccc(/C=C/c2nc3c(c(=O)n(CC)c(=O)n3CC)n2C)cc1 | null | 90.9 | null |
1,136,586 | ord_dataset-aaeaab5f3720492494c1cbbdd0ed2820 | null | 2012-01-01T00:02:00 | true | CC[O-].[Na+].[S:5]1[CH:9]=[CH:8][CH:7]=[C:6]1[CH:10]=O.[C:12]([O:21]CC)(=[O:20])[CH2:13][CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16]>C(O)C>[CH2:18]([O:17][C:15]([C:14](=[CH:10][C:6]1[S:5][CH:9]=[CH:8][CH:7]=1)[CH2:13][C:12]([OH:21])=[O:20])=[O:16])[CH3:19] | O=Cc1cccs1 | CCOC(=O)CCC(=O)OCC | null | CC[O-] | [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 | null | null | Sodium ethylate (41.4 g, 0.61 mol) was added under vigorous stirring to a solution of thiophene-2-carbaldehyde (57 g, 0.51 mol) and diethyl succinate (176 g, 1.01 mol) in ethanol (1 L). The reaction mixture was refluxed for 3 h and evaporated in vacuum (˜20 mmHg) at 50° C. until the solvent distillation ceased. The obtained residue was diluted with 500 mL of 10% HCl and 500 mL of ethyl acetate. The mixture was shaken. The organic layer was separated, diluted with 300 mL of a saturated aqueous solution of NaHCO3, and shaken. The aqueous layer was separated, neutralized by 10% HCl to pH 2, and subjected to extraction by 1 L of ethyl acetate. The organic layer was evaporated in vacuum (˜20 mmHg) at 60° C. and chromatographed on a layer of silica gel (300×150 mm) with hexane/ethyl acetate mixture, 1:1 as eluent. Fractions with the target product were collected and evaporated in vacuum to give 60 g (0.25 mol, 49%) of 3-(ethoxycarbonyl)-4-thien-2-ylbut-3-enoic acid as a light-brown oil. | CCOC(=O)C(=Cc1cccs1)CC(=O)O | null | 49 | null |
986,773 | ord_dataset-35b56288528641309a040cc2b6710b61 | null | 2010-01-01T00:08:00 | true | [Cl:1][C:2]1[CH:3]=[C:4]([N:10]2[CH:18]([CH:19]3[CH2:23][CH2:22][CH2:21][CH2:20]3)[CH:17]3[C:12]([C:13]4[CH:27]=[CH:26][C:25]([C:28]([OH:30])=[O:29])=[CH:24][C:14]=4[CH2:15][CH2:16]3)=[N:11]2)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].[CH2:31](O)[CH2:32][O:33][CH2:34][CH2:35][O:36][CH2:37][CH2:38][OH:39]>>[Cl:1][C:2]1[CH:3]=[C:4]([N:10]2[CH:18]([CH:19]3[CH2:20][CH2:21][CH2:22][CH2:23]3)[CH:17]3[C:12]([C:13]4[CH:27]=[CH:26][C:25]([C:28]([O:30][CH2:31][CH2:32][O:33][CH2:34][CH2:35][O:36][CH2:37][CH2:38][OH:39])=[O:29])=[CH:24][C:14]=4[CH2:15][CH2:16]3)=[N:11]2)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9] | OCCOCCOCCO | N#Cc1ccc(N2N=C3c4ccc(C(=O)O)cc4CCC3C2C2CCCC2)cc1Cl | null | null | null | null | null | null | null | 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 (±)-(3SR,3aRS)-2-(3-chloro-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylic acid, Example 15 and triethylene glycol according to Method E (yellow solid, 125 mg, 0.226 mmol, 47% yield). ES-HRMS m/z calc. for C30H34ClN3NaO5 (M+Na) 574.2085, found 574.2047. | N#Cc1ccc(N2N=C3c4ccc(C(=O)OCCOCCOCCO)cc4CCC3C2C2CCCC2)cc1Cl | null | 47 | null |
167,422 | ord_dataset-fdef1f30cad64430bf05cf108d8004a2 | null | 1988-01-01T00:01:00 | true | [C:1]1([CH2:7][O:8][C:9]2[CH:10]=[C:11]([CH2:23][CH2:24][NH:25][CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH:12]=[CH:13][C:14]=2[O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40].C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>C(#N)C>[CH2:42]([O:41][C:39](=[O:40])[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34][N:25]([CH2:24][CH2:23][C:11]1[CH:12]=[CH:13][C:14]([O:15][CH2:16][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)=[C:9]([O:8][CH2:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH:10]=1)[CH2:26][C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1)[CH3:43] | c1ccc(CNCCc2ccc(OCc3ccccc3)c(OCc3ccccc3)c2)cc1 | CCOC(=O)CCCCCBr | null | O=C([O-])[O-] | [I-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC#N | null | null | null | null | null | null | null | null | null | null | null | null | A suspension of 3,4-bis(phenylmethoxy)-N-phenylmethyl benzeneethanamine (10 g), ethyl 6-bromohexanoate (10.5 g), potassium carbonate (6.34 g) and potassium iodide (1 g) in acetonitrile (250 ml) was heated under reflux for 24 hours. | CCOC(=O)CCCCCN(CCc1ccc(OCc2ccccc2)c(OCc2ccccc2)c1)Cc1ccccc1 | null | null | null |
1,715,168 | ord_dataset-3f2a531ffbae4b9eb1048afcd7953beb | null | 2016-01-01T00:04:00 | true | [F:1][C:2]1[CH:7]=[CH:6][C:5]([Mg]Br)=[CH:4][CH:3]=1.[F:10][C:11]1[CH:12]=[C:13](/[CH:18]=[CH:19]/[C:20]([N:22]2[C@H:26]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH2:25][O:24][C:23]2=[O:33])=[O:21])[CH:14]=[C:15]([F:17])[CH:16]=1>C1COCC1>[F:10][C:11]1[CH:12]=[C:13]([C@H:18]([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)[CH2:19][C:20]([N:22]2[C@H:26]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH2:25][O:24][C:23]2=[O:33])=[O:21])[CH:14]=[C:15]([F:17])[CH:16]=1 | O=C(/C=C/c1cc(F)cc(F)c1)N1C(=O)OC[C@H]1c1ccccc1 | Fc1ccc([Mg]Br)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 | -40 | 1.5 | A solution of 4-fluorophenylmagnesium bromide (29 mL of a 2.0 M solution in THF, 58 mmol) and copper(I) bromide-dimethylsulfide complex (12 g, 59 mmol) in THF (100 mL) under an atmosphere of nitrogen was cooled to −40° C. in a dry ice-acetonitrile bath. To the stirred solution was added a solution of (4R)-3-[(2E)-3-(3,5-difluorophenyl)prop-2-enoyl]-4-phenyl-1,3-oxazolidin-2-one (7.7 g, 23 mmol) in 100 mL of THF dropwise over 15 min. The resulting mixture was stirred at −40° C. for 1.5 h, then the cooling bath was removed and the stirred mixture was allowed to warm to ambient temperature. The reaction was quenched by the addition of aqueous NH4Cl solution. The resulting mixture was stirred for 15 min then extracted with two portions of EtOAc. The combined organic phases were washed with water and brine, then dried (MgSO4), filtered, and the solvents were removed in vacuo. The residue was chromatographed on a 330 g SiO2 column using a gradient elution of 0-50% EtOAc:A, where A=1:1 hexanes:CHCl3. Fractions containing product were combined and the solvents were removed in vacuo to give a solid. | O=C(C[C@@H](c1ccc(F)cc1)c1cc(F)cc(F)c1)N1C(=O)OC[C@H]1c1ccccc1 | null | null | null |
1,636,057 | ord_dataset-f0794d5ded7a4d3fab45cc3d7a89ee3d | null | 2015-01-01T00:09:00 | true | [N+:1]([C:4]1[CH:21]=[CH:20][C:19]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[C:6]=2[CH:5]=1)([O-])=O.NN>C(O)C.[Pd]>[NH2:1][C:4]1[CH:21]=[CH:20][C:19]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[C:6]=2[CH:5]=1 | O=[N+]([O-])c1ccc2c3ccccc3c3ccccc3c2c1 | null | null | [Pd] | NN | 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 | 2 | 3.1 g (11.3 mmol) of a mixture of 1 and 2-nitrotriphenylene (synthesized according to J. Chem. Soc., 1955, 4482) in about 100 mL of ethanol, 600 mg (0.57 mmol) of Pd/C (10% on activated carbon), and 2.3 g (45.2 mmol) of hydrazine monhydride were charged in a 250 mL round bottle flask. The reaction mixture was heated up to reflex under nitrogen for 2 hours. The reaction mixture was then filtered and the filtrate was concentrated and passed through a silica gel column using 25% ethyl acetate in hexanes as elute. 1 and 2 aminotriphenyl were separated and confirmed by MS and NMR. This reaction yield was 100%. | Nc1ccc2c3ccccc3c3ccccc3c2c1 | null | 100 | null |
725,886 | ord_dataset-0387783899c642a8b7eb4ba379bcdf5d | null | 2006-01-01T00:08:00 | true | [NH2:1][C:2]1[S:3][C:4]([C:11]2[CH:20]=[CH:19][C:14]3[O:15][CH2:16][CH2:17][O:18][C:13]=3[CH:12]=2)=[C:5]([CH3:10])[C:6]=1[C:7]([NH2:9])=[O:8].ClC(Cl)(Cl)[C:23]([N:25]=C=O)=[O:24].N>O1CCCC1.CO>[NH2:25][C:23]([NH:1][C:2]1[S:3][C:4]([C:11]2[CH:20]=[CH:19][C:14]3[O:15][CH2:16][CH2:17][O:18][C:13]=3[CH:12]=2)=[C:5]([CH3:10])[C:6]=1[C:7]([NH2:9])=[O:8])=[O:24] | Cc1c(-c2ccc3c(c2)OCCO3)sc(N)c1C(N)=O | O=C=NC(=O)C(Cl)(Cl)Cl | null | N | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | CO | null | null | null | null | null | null | null | null | null | 0 | 0.5 | 2-Amino-4-methyl-5-(1,4-benzodioxan-6-yl)-3-thiophencarboxamide (0.44 g) was dissolved in tetrahydrofuran (10 ml), cooled to 0° C. and trichloroacetylisocyanate (0.11 ml) added dropwise with stirring. Stirring was continued for a further 30 minutes at room temperature and then a solution of ammonia in methanol (8 ml of a 10% solution) was added and stirring was continued for a further 3 h. The solvent was evaporated and the residue treated with ethyl acetate and the product filtered off. | Cc1c(-c2ccc3c(c2)OCCO3)sc(NC(N)=O)c1C(N)=O | null | null | null |
462,947 | ord_dataset-5ca9db262dd24c5a9315cdc8ef055b7e | null | 2000-01-01T00:04:00 | true | [OH:1][CH:2]1[CH:7]([C:8]2[CH:13]=[CH:12][C:11]([CH2:14][OH:15])=[CH:10][CH:9]=2)[CH2:6][CH2:5][N:4]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:3]1.Br[CH2:24][C:25]1[CH:34]=[CH:33][C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:26]=1>>[CH:26]1[C:27]2[C:32](=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:33]=[CH:34][C:25]=1[CH2:24][O:1][CH:2]1[CH:7]([C:8]2[CH:9]=[CH:10][C:11]([CH2:14][O:15][CH2:24][C:25]3[CH:34]=[CH:33][C:32]4[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=4)[CH:26]=3)=[CH:12][CH:13]=2)[CH2:6][CH2:5][N:4]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:3]1 | BrCc1ccc2ccccc2c1 | CC(C)(C)OC(=O)N1CCC(c2ccc(CO)cc2)C(O)C1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | In an analogous manner to that described in Example 22(i), by alkylating tert-butyl (3RS,4RS)-3-hydroxy-4-(4-hydroxymethyl-phenyl)-piperidine-1-carboxylate with 2-bromomethylnaphthalene there was obtained tert-butyl (3RS,4RS)-3-(naphthalen-2-ylmethoxy)-4-[4-(naphthalen-2-ylmethoxymethyl)-phenyl]-piperidine-1-carboxylate as a colourless oil, Rf : 0.31 (SiO2, hexane:ethyl acetate=2:1). | CC(C)(C)OC(=O)N1CCC(c2ccc(COCc3ccc4ccccc4c3)cc2)C(OCc2ccc3ccccc3c2)C1 | null | null | null |
1,187,055 | ord_dataset-9cd817a75dfc4fe7ad19d4232772d5ff | null | 2012-01-01T00:07:00 | true | [C:1]([O:5][C:6]([N:8]1[C:12]2[CH:13]=[C:14]([CH:17]([OH:22])[C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1[C:23]1[C:28]([CH3:29])=[CH:27][CH:26]=[CH:25][C:24]=1[CH3:30])=[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[C:12]2[CH:13]=[C:14]([C:17](=[O:22])[C:18]([F:19])([F:20])[F:21])[CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1[C:23]1[C:28]([CH3:29])=[CH:27][CH:26]=[CH:25][C:24]=1[CH3:30])=[O:7])([CH3:4])([CH3:3])[CH3:2] | Cc1cccc(C)c1-c1nc2ccc(C(O)C(F)(F)F)cc2n1C(=O)OC(C)(C)C | 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 | 25 | 18 | To a solution of 2-(2,6-dimethylphenyl)-6-(2,2,2-trifluoro-1-hydroxyethyl)-benzoimidazole-1-carboxylic acid tert-butyl ester (475 mg) in methylene chloride (15 mL) was added Dess-Martin reagent (527 mg) and the mixture was stirred at ambient temperature for 18 h. The mixture was washed with water and sodium bicarbonate solution then was dried over sodium sulfate. The solvent was removed under reduced pressure to give 2-(2,6-dimethylphenyl)-6-(2,2,2-trifluoroacetyl)-benzoimidazole-1-carboxylic acid tert-butyl ester as a gummy solid. The material was used directly in the next reaction. | Cc1cccc(C)c1-c1nc2ccc(C(=O)C(F)(F)F)cc2n1C(=O)OC(C)(C)C | null | null | null |
1,697,536 | ord_dataset-54347fcace774f89850681d6dec8009f | null | 2016-01-01T00:03:00 | true | [CH3:1][C:2]1([O:15][CH2:16][CH2:17][CH:18]=O)[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.C1(P(C2C=CC=CC=2)(C2C=CC=CC=2)=[CH:27][C:28](=[O:30])[CH3:29])C=CC=CC=1.O>C(Cl)Cl>[CH3:1][C:2]1([O:15][CH2:16][CH2:17]/[CH:18]=[CH:27]/[C:28](=[O:30])[CH3:29])[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:12])([CH3:13])[CH3:14])=[O:9])[CH2:6][CH2:7]1 | CC(=O)C=P(c1ccccc1)(c1ccccc1)c1ccccc1 | CC(C)(C)OC(=O)N1CCC(C)(OCCC=O)CC1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | O | null | null | null | null | null | null | null | null | null | 25 | 16 | To a solution of tert-butyl 4-methyl-4-(3-oxopropoxy)piperidine-1-carboxylate (5.7 g, 21.01 mmol) in CH2Cl2 (150 mL) was added 1-(triphenylphosphoranylidene)propan-2-one (8.69 g, 27.3 mmol) and the resulting mixture was stirred at room temp for 16 h. Water was then added and the mixture was extracted with dichloromethane, dried (Na2SO4), filtered and concentrated. The residue was then purified by Biotage (5-40% EtOAc/hexane) to afford (E)-tert-butyl 4-methyl-4-((5-oxohex-3-en-1-yl)oxy)piperidine-1-carboxylate (5.25 g, 16.86 mmol, 80% yield) as colorless oil. 1H NMR (500 MHz, CDCl3) δ 6.85 (dt, J=16.1, 6.9 Hz, 1H), 6.15 (dt, J=16.0, 1.4 Hz, 1H), 3.79-3.66 (m, 2H), 3.47 (t, J=6.4 Hz, 2H), 3.12 (t, J=11.6 Hz, 2H), 2.49 (qd, J=6.5, 1.5 Hz, 2H), 2.29-2.26 (m, 3H), 1.73 (d, J=13.2 Hz, 2H), 1.47 (s, 9H), 1.46-1.39 (m, 2H), 1.18 (s, 3H). LCMS (M+Na)=334.3. | CC(=O)/C=C/CCOC1(C)CCN(C(=O)OC(C)(C)C)CC1 | null | 80.2 | null |
883,442 | ord_dataset-3592bd645cd143ee8274cd0d834ae581 | null | 2009-01-01T00:05:00 | true | [C:1]1([C:16]2[NH:20][C:19]3[CH:21]=[CH:22][CH:23]=[CH:24][C:18]=3[N:17]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[NH:11][C:10]2[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=2[N:8]=1.[H-].[Na+]>CN(C)C=O>[C:2]1([C:7]2[N:11]([CH2:12][CH2:10][CH2:9][CH2:15][CH3:14])[C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[N:8]=2)[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=1[C:16]1[N:17]([CH2:3][CH2:2][CH2:1][CH2:6][CH3:5])[C:18]2[CH:24]=[CH:23][CH:22]=[CH:21][C:19]=2[N:20]=1 | c1ccc(-c2nc3ccccc3[nH]2)c(-c2nc3ccccc3[nH]2)c1 | null | null | [H-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | null | 0.5 | To a flask were added 1.5 g of 2,2′-(1,2-phenylene)bis(1H-benzimidazole) and 30 ml of N,N-dimethylformamide, and the mixture was cooled to 5 C. To this mixture was added 0.48 g of 60% sodium hydride in mineral oil in small portions, and after stirring at 5-10 C for 30 minutes, 2.4 g of 1-1-iodopentane were added. The reaction mixture was warmed to 22 C for and stirred for 16 hours, then quenched with 50 ml water. The product was extracted with 40 ml ethyl acetate and following removal of the solvent, the product was purified by silica gel chromatography using 25% ethyl acetate, 75% hexane and 0.1% triethylamine resulting in 2.1 g of a yellow solid. | CCCCCn1c(-c2ccccc2-c2nc3ccccc3n2CCCCC)nc2ccccc21 | null | null | null |
653,203 | ord_dataset-fe016e2f90e741a590ad77fd5933161f | null | 2004-01-01T00:11:00 | true | [Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[C:4]([F:10])[CH:3]=1.[CH3:11]C(C)([O-])C.[K+]>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CCOCC>[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[CH2:11])=[C:4]([F:10])[CH:3]=1 | CC(C)(C)[O-] | O=Cc1ccc(Br)cc1F | null | C[P+](c1ccccc1)(c1ccccc1)c1ccccc1 | [Br-] | [K+] | 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 | 1 | To a stirred suspension of 4-bromo-2-fluoro-benzaldehyde (Aldrich, 2.30 g, 11.3 mmol) and methyltriphenylphosphonium bromide(Aldrich, 4.93 g, 13.6 mmol) in ether (50 mL), potassium tert-butoxide(1.52 g, 13.6 mmol) was added and the mixture was stirred at room temperature for 1 hour. The solid was filtered off and the filtrate was concentrated. The residue was treated with 30% ethyl acetate/hexanes (3 mL) and the solid was removed by filtration. The filtrate was filtered through a silica gel pad eluting with 30% ethyl acetate/hexanes to give a yellow oil. 1.54 g, 68%. | C=Cc1ccc(Br)cc1F | null | null | null |
273,164 | ord_dataset-ee287d49cb8642e59ae9c3951f746312 | null | 1993-01-01T00:08:00 | true | [C:1]([C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([C:11]([CH3:14])([CH3:13])[CH3:12])[C:6]=1[OH:15])([CH3:4])([CH3:3])[CH3:2].[CH3:16][C:17]1[O:21][N:20]=[C:19]([C:22](Cl)=[O:23])[CH:18]=1.[Al+3].[Cl-].[Cl-].[Cl-]>C(=S)=S>[CH3:12][C:11]([C:7]1[CH:8]=[C:9]([C:22]([C:19]2[CH:18]=[C:17]([CH3:16])[O:21][N:20]=2)=[O:23])[CH:10]=[C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[C:6]=1[OH:15])([CH3:14])[CH3:13] | Cc1cc(C(=O)Cl)no1 | CC(C)(C)c1cccc(C(C)(C)C)c1O | null | [Al+3] | [Cl-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | S=C=S | null | null | null | null | null | null | null | null | null | null | null | 1 | To a solution of 20.6 g (0.1 mole) of 2,6-di-tert-butylphenol and 15.6 g (0.107 mole) of 5-methylisoxazole-3-carboxylic acid chloride in 100 mL of CS2 is added 14.3 g (0.107 mole) of AlCl3 at +5° C. Vigorous stirring is maintained at that temperature for 1 hour and then at room temperature for 1 hour. The CS2 is decanted off and the residue treated with 350 mL of ice cold IN HCl and extracted with Et2O. The extracts are washed with saturated NaHCO3 solution and brine, dried with Na2SO4 and evaporated to give a mixture of products. The desired product is separated by flash chromatography (0% to 50% CH2Cl2 /n hexane) on silica gel to give 4.4 g of the crude ketone which is recrystallized from n-pentane to give 2.3 g (14%) of pale yellow crystals, [3,5-bis(1,1 dimethylethyl)-4 -hydroxyphenyl(5-methyl-3-isoxazolyl)methanone, mp 120° C.; 1H NMR (CDCl3)δ1.48 (s, 18H, tert-butyl), 2.52 (s, 3H, CH3), 5.85 (s, 1H, OH), 6.48 (s, 1H, isoxazole aromatic), 8.23 (s, 2H, phenyl aromatics); IR (KBr) 1590, 1600, 1650, 3600 cm-1 ; MS (DEI) m/e 315 (M+), 300 (M-CH3). | Cc1cc(C(=O)c2cc(C(C)(C)C)c(O)c(C(C)(C)C)c2)no1 | null | 14 | null |
348,487 | ord_dataset-66f304805e5d47fc8d3c722b1bd8dfa2 | null | 1996-01-01T00:12:00 | true | [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH:6]([NH2:8])[CH3:7].[CH:9]([C:12]1[N:16]=[C:15]([C:17](OCC)=[O:18])[S:14][N:13]=1)([CH3:11])[CH3:10]>C1(C)C=CC=CC=1>[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH:6]([NH:8][C:17]([C:15]1[S:14][N:13]=[C:12]([CH:9]([CH3:11])[CH3:10])[N:16]=1)=[O:18])[CH3:7] | CCOC(=O)c1nc(C(C)C)ns1 | CC(N)c1cccs1 | 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 | 80 | 3 | (R/S)-1-Thiophen-2-yl-ethylamine (19.05 g, 0.150 mol) is added to a stirred solution of ethyl 3-isopropyl-[1,2,4]thiadiazole-5-carboxylate (25.0 g, 0.125 mol) in toluene (50 ml) and the mixture is heated to 80° C. for 2 hours. A further portion of (R/S)-1-[(2-thienyl)ethyl]amine (10.0 g, 0.08 mol) is added to the mixture, which is heated at 80° C. for a further 2 hours. Then a further portion of (R/S)-1-[(2-thienyl)ethyl]amine (10.0 g, 0.08 mol) is added to the mixture, and stirring is continued for a further 3 hours at 80° C. The solvent is evaporated in vacuo, and the residue is dissolved in methyl tert-butyl ether. The resulting solution is washed two times with 1N hydrochloric acid, dried with magnesium sulphate and the solvent is evaporated in vacuo. The oily residue is dissolved in petroleum ether (50 ml) and, upon agitation, the product crystallises out of the solution. The crystalline product is filtered off, washed with a small amount of petroleum ether and dried, to give (R/S)-3-isopropyl-[1,2,4]thiadiazole-5-carboxylic acid, [1-(2-thienyl)ethyl]amide (22.3 g, 63%) as beige crystals, m.p. 61°-63° C. | CC(C)c1nsc(C(=O)NC(C)c2cccs2)n1 | null | 63.4 | null |
1,489,115 | ord_dataset-c3c1091f873b4f40827973a6f1f9b685 | null | 2014-01-01T00:09:00 | true | Cl.[O:2]=[C:3]1[NH:12][C:11]2[N:10]=[CH:9][C:8](/[CH:13]=[CH:14]/[C:15]([OH:17])=O)=[CH:7][C:6]=2[CH2:5][CH2:4]1.Cl.[S:19]1[CH:23]=[CH:22][CH:21]=[C:20]1[CH2:24][O:25][CH:26]1[CH2:29][NH:28][CH2:27]1.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C>CN(C=O)C>[O:17]=[C:15]([N:28]1[CH2:29][CH:26]([O:25][CH2:24][C:20]2[S:19][CH:23]=[CH:22][CH:21]=2)[CH2:27]1)/[CH:14]=[CH:13]/[C:8]1[CH:7]=[C:6]2[C:11](=[N:10][CH:9]=1)[NH:12][C:3](=[O:2])[CH2:4][CH2:5]2 | c1csc(COC2CNC2)c1 | O=C(O)/C=C/c1cnc2c(c1)CCC(=O)N2 | null | CCN=C=NCCCN(C)C | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(C(C)C)C(C)C | CN(C)C=O | null | null | null | null | null | null | null | null | null | 25 | 8 | A 16 mL vial flask was successively charged with (2E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylic acid hydrochloride (30 mg, 0.12 mmol), DMF (3 mL), 3-(2-thienylmethoxy)azetidine hydrochloride (29 mg, 0.14 mmol; which may be prepared as described in Step 3), DIPEA (48 μL, 0.28 mmol) and EDAC (27 mg, 0.14 mmol). The reaction mixture was stirred at room temperature overnight and concentrated to dryness. The residue was purified on preparative TLC (eluent: dichloromethane/NH3 7N in MeOH, 2.5%) to give a brown solid. This solid was triturated in acetone and diethyl ether, filtered, washed with diethyl ether then dried to give the title compound (8 mg, 18%) as a pale brown solid. | O=C1CCc2cc(/C=C/C(=O)N3CC(OCc4cccs4)C3)cnc2N1 | null | 18 | null |
1,262,183 | ord_dataset-266f60b4555945d6afb2d2bdf5fa04e0 | null | 2013-01-01T00:02:00 | true | C[O:2][CH:3](OC)[C:4]1[CH:5]=[C:6]([S:13][C:14]2[CH:15]=[C:16]([NH:20][S:21]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)(=[O:23])=[O:22])[CH:17]=[CH:18][CH:19]=2)[CH:7]=[CH:8][C:9]=1[N+:10]([O-:12])=[O:11].O>Cl.C1COCC1>[CH:3]([C:4]1[CH:5]=[C:6]([S:13][C:14]2[CH:15]=[C:16]([NH:20][S:21]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)(=[O:23])=[O:22])[CH:17]=[CH:18][CH:19]=2)[CH:7]=[CH:8][C:9]=1[N+:10]([O-:12])=[O:11])=[O:2] | COC(OC)c1cc(Sc2cccc(NS(=O)(=O)c3ccccc3)c2)ccc1[N+](=O)[O-] | null | null | Cl | 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 | 8 | A mixture of N-[3-(3-dimethoxymethyl-4-nitro-phenylsulfanyl)-phenyl]-benzenesulfonamide (0.027 mol) in 12N HCl (25 mL), THF (75 mL), and water (50 mL) was stirred overnight at room temperature, and then the mixture was extracted with EtOAc. The extract was washed with H2O and then with a saturated Na2CO3 solution. The solvent was evaporated, and the residue was purified by column chromatography over silica gel (eluent: CH2Cl2). The product fractions were collected and the solvent was evaporated to yield the title compound as a residue. | O=Cc1cc(Sc2cccc(NS(=O)(=O)c3ccccc3)c2)ccc1[N+](=O)[O-] | null | null | null |
763,003 | ord_dataset-2e58cb8db2bf482bbea23283b7e04488 | null | 2007-01-01T00:03:00 | true | [F:1][C:2]([F:15])([F:14])[CH2:3][O:4][C:5]1[CH:13]=[CH:12][CH:11]=[CH:10][C:6]=1[C:7]([OH:9])=[O:8].[Al+3].[Cl-].[Cl-].[Cl-].[Br:20]Br>C(Cl)Cl>[Br:20][C:11]1[CH:12]=[CH:13][C:5]([O:4][CH2:3][C:2]([F:14])([F:15])[F:1])=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8] | O=C(O)c1ccccc1OCC(F)(F)F | BrBr | null | [Al+3] | [Cl-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | 0 | 1 | To a solution of 2-(2,2,2-trifluoroethoxy)benzoic acid (22 g) in methylene chloride (100 ml), was added AlCl3 (13.3 g) at 0° C.followed by bromine (16.0 g, 0.1 mol). The reaction mixture was stirred at 0° C. for 1 hour and then at reflux for 2 hours. The solids were filtered and water (50 ml) and ethyl acetate (50 ml) were added to the filtrate. The aqueous layer was separated and extracted with ethyl acetate (2×60 ml) and the combined organic layers were washed with water (2×60 ml). The organic layer was concentrated under vacuum to dryness and hexane (100 ml) was added and the resulting suspension was stirred at 20 to 25° C. for 1 hour. The mixture was filtered and the cake was rinsed with heptanes (2×20 ml). The damp solids were dried in vacuum at 45° C. for 5–6 hours to give a white solid (28.3 g, yield 94.6%), m.p. 126–128° C. | O=C(O)c1cc(Br)ccc1OCC(F)(F)F | null | 94.7 | null |
1,153,803 | ord_dataset-b195433d5c354ddfb6cde0d53c41910f | null | 2012-01-01T00:04:00 | true | [ClH:1].Br[C:3]1[C:7]2=[N:8][CH:9]=[CH:10][CH:11]=[C:6]2[S:5][C:4]=1[NH2:12]>CO.[Pd]>[ClH:1].[S:5]1[C:6]2[C:7](=[N:8][CH:9]=[CH:10][CH:11]=2)[CH:3]=[C:4]1[NH2:12] | Nc1sc2cccnc2c1Br | null | null | [Pd] | Cl | 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 | 3 | A mixture of compound 145-H, (1.86 g, 6.16 mmol) and 10% Pd/C (0.49 g, 26.3% w/w) in methanol (75 mL) was catalytically hydrogenated on a Parr shaker at 25 psi. After 3 h, the catalyst was filtered, the reaction mixture recharged with 10% Pd/C (0.49 g, 26.3% w/w) and shaken an additional 16 h at 22 psi H2. The reaction was filtered, recharged with 10% Pd/C (0.20 g, 10.8% w/w), and shaken at 20 psi H2 for an additional 24 h. The reaction mixture was filtered, evaporated, and the free base isolated by washing with aqueous sodium bicarbonate. The resultant residue was purified by flash column chromatography (SiO2), eluting with 3% MeOH/CH2Cl2 to afford compound 146-A as a yellow solid (0.65 g, 57%). 1H-NMR (DMSO-d6): δ 6.4 (s, 1H), 7.1 (dd, 1H), 8.3 (2, 1H), 8.4 (s, 2H), 8.5 (d, 1H), 15.2 (br s, 1H); MS: m/z 151.1 (MH+). | Nc1cc2ncccc2s1 | null | 56.5 | null |
1,755,624 | ord_dataset-97eb2ab57fec4160922caae33b54d956 | null | 2016-01-01T00:08:00 | true | [C:1]([C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[N:11]([CH3:15])[C:10]([CH:16]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17]1)=[CH:9]2)(=O)[CH2:2][CH2:3][CH3:4].[CH3:28][O:29][C:30]1[CH:37]=[C:36]([O:38][CH3:39])[CH:35]=[CH:34][C:31]=1[CH2:32][NH2:33].CCN(CC)CC>C(Cl)Cl.Cl[Ti](Cl)(Cl)Cl>[CH3:28][O:29][C:30]1[CH:37]=[C:36]([O:38][CH3:39])[CH:35]=[CH:34][C:31]=1[CH2:32][N:33]=[C:1]([C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[N:11]([CH3:15])[C:10]([CH:16]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:25])([CH3:27])[CH3:26])=[O:22])[CH2:17]1)=[CH:9]2)[CH2:2][CH2:3][CH3:4] | COc1ccc(CN)c(OC)c1 | CCCC(=O)c1ccc2c(c1)cc(C1CCN(C(=O)OC(C)(C)C)C1)n2C | null | Cl[Ti](Cl)(Cl)Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | CCN(CC)CC | null | null | null | null | null | null | null | null | null | 25 | 8 | To solution of tert-butyl 3-(5-butyryl-1-methyl-1H-indol-2-yl)pyrrolidine-1-carboxylate (0.823 g, 2.22 mmol) in DCM (5 mL) was added 2,4-dimethoxybenzylamine (0.38 mL, 2.53 mmol) and NEt3 (0.90 mL, 6.45 mmol). Mixture was cooled to 0° C. before TiCl4 solution (1M DCM, 1.45 mL, 1.45 mmol) was added dropwise via syringe pump over 30 min. Reaction was allowed to warm to room temperature and stirred overnight. Mixture was diluted with DCM (10 mL) and then quenched with NaHCO3 (aqueous saturated, 10 mL). Upon vigorous shaking organic phase was separated using a PTFE phase separator, dried over Na2SO4. Removal of the solvent afforded product (1.15 g, quant) as yellow oil, which was taken directly into next steps without purification. | CCCC(=NCc1ccc(OC)cc1OC)c1ccc2c(c1)cc(C1CCN(C(=O)OC(C)(C)C)C1)n2C | null | null | null |
1,619,533 | ord_dataset-35c51552812941cda45194a013d34bb9 | null | 2015-01-01T00:08:00 | true | [F:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([NH2:12])[CH:11]=1)[N:8]=[CH:7][CH:6]=[CH:5]2.[C:13]([C:15]1[N:20]=[CH:19][C:18]([S:21](Cl)(=[O:23])=[O:22])=[CH:17][CH:16]=1)#[N:14].N1C=CC=CC=1>CN(C1C=CN=CC=1)C.C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([NH:12][S:21]([C:18]3[CH:19]=[N:20][C:15]([C:13]#[N:14])=[CH:16][CH:17]=3)(=[O:22])=[O:23])[CH:11]=1)[N:8]=[CH:7][CH:6]=[CH:5]2 | N#Cc1ccc(S(=O)(=O)Cl)cn1 | Nc1cc(F)cc2cccnc12 | null | CN(C)c1ccncc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | c1ccncc1 | null | null | null | null | null | null | null | null | null | null | null | In a similar fashion using route 14 general procedure 27, 6-fluoroquinolin-8-ylamine (Intermediate 48) (125 mg, 0.77 mmol), 6-cyano-pyridine-3-sulfonyl chloride (Intermediate 19) (187 mg, 0.92 mmol), pyridine (121 mg, 1.54 mmol), DMAP (cat.) and DCM (10 ml) gave the title compound (67 mg, 26%) after purification by column chromatography with n-hexane/DCM (50:50) as the eluent. | N#Cc1ccc(S(=O)(=O)Nc2cc(F)cc3cccnc23)cn1 | null | 26.5 | null |
1,260,444 | ord_dataset-266f60b4555945d6afb2d2bdf5fa04e0 | null | 2013-01-01T00:02:00 | true | [CH2:1]([N:8]1[CH2:42][CH2:41][C:11]2([N:15]([C:16]3[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=3[C:23]3[CH:28]=[CH:27][C:26]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:25][CH:24]=3)[C:14](=[O:33])[N:13]=[C:12]2[NH:34][CH2:35][CH:36](OC)OC)[CH2:10][CH:9]1[CH3:43])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[CH2:1]([N:8]1[CH2:42][CH2:41][C:11]2([C:12]3=[N:34][CH:35]=[CH:36][N:13]3[C:14](=[O:33])[N:15]2[C:16]2[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=2[C:23]2[CH:28]=[CH:27][C:26]([S:29]([CH3:32])(=[O:30])=[O:31])=[CH:25][CH:24]=2)[CH2:10][CH:9]1[CH3:43])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1 | COC(CNC1=NC(=O)N(c2cc(F)ccc2-c2ccc(S(C)(=O)=O)cc2)C12CCN(Cc1ccccc1)C(C)C2)OC | null | null | Cc1ccc(S(=O)(=O)O)cc1 | 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 | 110 | null | To a solution of 8-benzyl-4-[(2,2-dimethoxyethyl)amino]-1-[4-fluoro-4′-(methylsulfonyl)biphenyl-2-yl]-7-methyl-1,3,8-triazaspiro[4.5]dec-3-en-2-one (50 mg, 0.08 mmol) in toluene (2.0 ml) was added p-toluenesulfonic acid (20 mg, 0.01 mmol). The reaction was sealed and allowed to stir at 110° C. The reaction was purified via reverse phase chromatography and neutralized with sodium bicarbonate. The product was extracted with EtOAc, dried over sodium sulfate, filtered, and concentrated in vacuo to yield the title compound as cis and trans mixture-1′-benzyl-6-[4-fluoro-4′-(methylsulfonyl)biphenyl-2-yl]-2′-methylspiro[imidazo[1,5-a]imidazole-7,4′-piperidin]-5(6H)-one. LCMS (M+H) 544.9. 1H NMR (400 MHz, CD3OD) δ 7.98 (m, 1H), 7.89 (m, 1H), 7.66 (m, 3H), 7.55 (m, 1H), 7.46 (m, 1H), 7.40 (dt, J=8.8, 2.8 Hz, 0.5H), 7.32 (dt, J=9.2, 2.8 Hz, 0.5H), 7.22 (m, 5H), 6.91 (m, 0.5H), 6.79 (m, 0.5H), 4.10 (m, 1H), 3.12 (s, 1.5H), 3.06 (s, 1.5H), 3.02 (s, 1H), 2.81 (m, 1H), 2.71-2.40 (m, 2H), 2.04-1.85 (m, 1H), 1.78-1.57 (m, 3H), 1.32 (s, 3H). | CC1CC2(CCN1Cc1ccccc1)c1nccn1C(=O)N2c1cc(F)ccc1-c1ccc(S(C)(=O)=O)cc1 | null | null | null |
1,293,819 | ord_dataset-de51ecc8d4434bacaa8bc32d7d73484c | null | 2013-01-01T00:05:00 | true | [NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].[Cl:11][C:12]1[N:17]=[C:16](Cl)[C:15]([Cl:19])=[CH:14][N:13]=1.Cl>CC(O)C>[Cl:11][C:12]1[N:17]=[C:16]([NH:1][C:2]2[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=2[C:4]([NH2:6])=[O:5])[C:15]([Cl:19])=[CH:14][N:13]=1 | Clc1ncc(Cl)c(Cl)n1 | NC(=O)c1ccccc1N | null | Cl | 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 | 60 | null | A mixture of 2-aminobenzamide (681 mg, 5.0 mmol), 2,4,5-trichloropyrimidine (2.75 g, 15 mmol, 3 equiv.) and concentrated HCl (aq) (1.72 mL, 20 mmol, 4 equiv.) in 2-propanol (100 mL) is heated at 60° C. for 12 h. The 2-propanol solvent is removed in vacuo. The resulting residue is neutralized to approximately pH=7 by adding 1 N NaOH (aq) followed by partition between EtOAc and water. Upon partition between EtOAc and water, a significant amount of precipitate is produced. This precipitate is collected by vacuum filtration and washed with small amounts of EtOAc and water, providing the product 2-(2,5-dichloropyrimidin-4-ylamino)benzamide; ESMS m/z 283.0 (M+H+). | NC(=O)c1ccccc1Nc1nc(Cl)ncc1Cl | null | null | null |
833,928 | ord_dataset-ec576c604a9d47258c87c732a043ec71 | null | 2008-01-01T00:08:00 | true | Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][NH:8]2)=[C:4]([N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[N:3]=1.[CH3:17][O:18][C:19]1[CH:20]=[C:21]([CH2:27][CH2:28][NH2:29])[CH:22]=[CH:23][C:24]=1[O:25][CH3:26]>CO>[CH3:17][O:18][C:19]1[CH:20]=[C:21]([CH2:27][CH2:28][NH:29][C:2]2[N:10]=[C:9]3[C:5]([N:6]=[CH:7][NH:8]3)=[C:4]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)[N:3]=2)[CH:22]=[CH:23][C:24]=1[O:25][CH3:26] | Clc1nc(N2CCOCC2)c2nc[nH]c2n1 | COc1ccc(CCN)cc1OC | 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 | 192.5 | 1 | As shown in Scheme 3 above, a mixture of 2,6-dichloropurine (1.90 g, 10 mmol) and morpholine (2.34 g, 30 mmol) in water (25 mL) was heated under reflux for 15 min. Solidified reaction mixture was cooled to room temperature. Solid was filtered out and washed with water, methanol and ether. The 2-chloro-6-morpholin-4-yl-9H-purine was obtained in 96% yield (2.30 g). A mixture of 2-chloro-6-morpholin-4-yl-9H-purine (1.92 g, 8 mmol) and 2-(3,4-dimethoxyphenyl)ethylamine (4.35 g, 24 mmol) in sealed tube and under nitrogen was stirred at 190-195° C. for 1 hour. The reaction mixture turned to clear solution initially and then formed a slurry. The reaction mixture was cooled to room temperature diluted with methanol (8 mL) and the solid was collected by filtration, washed with methanol and Et2O and dried to afford 2.30 g (74% yield) of [2-(3,4-dimethoxy-phenyl)-ethyl]-(6-morpholin-4-yl-9H-purin-2-yl)amine. | COc1ccc(CCNc2nc(N3CCOCC3)c3nc[nH]c3n2)cc1OC | null | 74.8 | null |
1,070,406 | ord_dataset-5df93261afc143c3ae919a57ff4fc1d4 | null | 2011-01-01T00:07:00 | true | [O-]CC.[Na+].[CH2:5]([C:9]([NH2:11])=[O:10])[C:6]([NH2:8])=[NH:7].Cl.Br[CH2:14][C:15]([C:17]1[CH:22]=[CH:21][C:20]([Br:23])=[CH:19][CH:18]=1)=O>C(O)C>[NH2:7][C:6]1[NH:8][C:15]([C:17]2[CH:22]=[CH:21][C:20]([Br:23])=[CH:19][CH:18]=2)=[CH:14][C:5]=1[C:9]([NH2:11])=[O:10] | O=C(CBr)c1ccc(Br)cc1 | N=C(N)CC(N)=O | null | CC[O-] | Cl | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | null | null | null | null | null | null | null | null | null | null | null | 0.33 | Under ice-cooling, sodium ethoxide (2.1 g, 30 mmol) was added to a suspension of malonamamidine hydrochloride (4.1 g, 30 mmol) in dehydrated ethanol (50 mL), and then the mixture was stirred for 20 minutes. Moreover, 2,4′-dibromoacetophenone (4.2 g, 15 mmol) was added thereto, and the whole was stirred at room temperature for 5 hours. After the insoluble solid was filtered out, the filtrate was concentrated in vacuo. The obtained residue was purified by silica gel column chromatography to give the title reference compound (0.37 g) as a black solid (Yield 9%). | NC(=O)c1cc(-c2ccc(Br)cc2)[nH]c1N | null | 8.8 | null |
1,719,833 | ord_dataset-3f2a531ffbae4b9eb1048afcd7953beb | null | 2016-01-01T00:04:00 | true | [CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:16]2[C:24]3[C:19](=[N:20][CH:21]=[N:22][C:23]=3[NH2:25])[NH:18][N:17]=2)[CH:12]=[C:13]([F:15])[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].Br[CH:33]([C:35]1[O:36][C:37](=[O:60])[C:38]2[C:43]([C:44]=1[C:45]1[CH:50]=[CH:49][CH:48]=[C:47]([CH:51]3[O:55][C:54]([CH3:57])([CH3:56])[C:53]([CH3:59])([CH3:58])[O:52]3)[CH:46]=1)=[CH:42][CH:41]=[CH:40][CH:39]=2)[CH3:34].Cl>CN(C=O)C.CCOC(C)=O>[NH2:25][C:23]1[N:22]=[CH:21][N:20]=[C:19]2[N:18]([CH:33]([C:35]3[O:36][C:37](=[O:60])[C:38]4[C:43]([C:44]=3[C:45]3[CH:50]=[CH:49][CH:48]=[C:47]([CH:51]5[O:52][C:53]([CH3:59])([CH3:58])[C:54]([CH3:57])([CH3:56])[O:55]5)[CH:46]=3)=[CH:42][CH:41]=[CH:40][CH:39]=4)[CH3:34])[N:17]=[C:16]([C:11]3[CH:12]=[C:13]([F:15])[CH:14]=[C:9]([O:8][CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)[CH:10]=3)[C:24]=12 | Nc1ncnc2[nH]nc(-c3cc(F)cc(OCc4ccccc4)c3)c12 | CC(Br)c1oc(=O)c2ccccc2c1-c1cccc(C2OC(C)(C)C(C)(C)O2)c1 | null | Cl | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | CCOC(C)=O | null | null | null | null | null | null | null | null | null | 60 | 0.25 | In a 100 ml round bottomed flask 3-(3-(benzyloxy)-5-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (Intermediate G18, 400 mg, 1,194 mmol) was dissolved in 7 ml of dry DMF then K2CO3 (254 mg, 1.837 mmol) was added. After stirring for 5 min a solution of 3-(1-bromoethyl)-4-(3-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)phenyl)-1H-isochromen-1-one (Intermediate C26, 420 mg, 0,918 mmol) in 7 ml of dry DMF was added and the clear brown mixture was heated at 60° C. for 30 min. The mixture was cooled to r.t. then 30 ml of HCl 0.5 M and 50 ml of EtOAc were added and stirred for 15 min. Phases were separated and the crude material was purified by chromatography eluting with DCM\MeOH (80/20) in DCM to give the title compound (820 mg) as a brown oil. This material was used in the next step without any further purification. | CC(c1oc(=O)c2ccccc2c1-c1cccc(C2OC(C)(C)C(C)(C)O2)c1)n1nc(-c2cc(F)cc(OCc3ccccc3)c2)c2c(N)ncnc21 | null | 0.1 | null |
1,708,367 | ord_dataset-54347fcace774f89850681d6dec8009f | null | 2016-01-01T00:03:00 | true | [Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([CH:21]([CH2:24][CH3:25])[CH2:22][CH3:23])[C:11](=[O:26])[C@:10]([CH2:28][C:29]([NH:31][NH:32][C:33]([NH2:35])=[O:34])=O)([CH3:27])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.Cl>[OH-].[Na+]>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([CH:21]([CH2:24][CH3:25])[CH2:22][CH3:23])[C:11](=[O:26])[C@@:10]([CH3:27])([CH2:28][C:29]3[NH:35][C:33](=[O:34])[NH:32][N:31]=3)[CH2:9]2)[CH:5]=[CH:6][CH:7]=1 | CCC(CC)N1C(=O)[C@@](C)(CC(=O)NNC(N)=O)C[C@H](c2cccc(Cl)c2)[C@H]1c1ccc(Cl)cc1 | 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 | 25 | null | 259 mg (0.50 mmol) of 2-(2-((3R,5R,6S)-5-(3-Chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-(pentan-3-yl)piperidin-3-yl)acetyl)hydrazinecarboxamide (Example 76, Step A) was suspended in 2 N aqueous sodium hydroxide (16 mL) and heated at reflux for 3.25 h. Upon cooling to room temperature, the mixture was acidified with conc. HCl until strongly acidic and then extracted with EtOAc (3×). The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated. Purification of the residue by reversed phase prep. HPLC (Sunfire™ Prep C18 OBD 10 μm column (Waters, Milford, Mass.), gradient elution of 40% MeCN in water to 75% MeCN in water over a 30 min period, where both solvents contain 0.1% TFA) provided the title compound as a white solid. | CCC(CC)N1C(=O)[C@@](C)(Cc2n[nH]c(=O)[nH]2)C[C@H](c2cccc(Cl)c2)[C@H]1c1ccc(Cl)cc1 | null | null | null |
970,848 | ord_dataset-03ba810b7f464a06b5d8787af2e8b64e | null | 2010-01-01T00:06:00 | true | [N+:1]([C:4]1[CH:5]=[C:6]([C:10]2[CH:11]=[C:12]3[C:16](=[CH:17][CH:18]=2)[CH2:15][CH:14]([NH:19][S:20]([CH:23]([CH3:25])[CH3:24])(=[O:22])=[O:21])[CH2:13]3)[CH:7]=[CH:8][CH:9]=1)([O-])=O>C(O)C.[Pd]>[NH2:1][C:4]1[CH:5]=[C:6]([C:10]2[CH:11]=[C:12]3[C:16](=[CH:17][CH:18]=2)[CH2:15][CH:14]([NH:19][S:20]([CH:23]([CH3:25])[CH3:24])(=[O:22])=[O:21])[CH2:13]3)[CH:7]=[CH:8][CH:9]=1 | CC(C)S(=O)(=O)NC1Cc2ccc(-c3cccc([N+](=O)[O-])c3)cc2C1 | null | null | [Pd] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | null | null | null | null | null | null | null | null | null | null | 25 | 24 | A solution of Intermediate 3 (430 mg, 1.19 mmol) in ethanol (10 ml) was treated with 10% palladium on charcoal (paste) (100 mg), and then stirred under an atmosphere of hydrogen at room temperature and pressure for 24 h. The mixture was filtered through a bed of kieselguhr and washed through with ethanol. The filtrate was removed under reduced pressure to give the title compound as a colourless solid (320 mg, 81%); mass spectrum: (ES−): Found 329 (MH−); C18H22N2O2S requires 330; 1H-NMR (400 MHz, CDCl3) δ 1.36 (6H, m), 2.94 (2H, m), 3.17 (1H, m), 3.35 (2H, m), 3.77 (2H, bs), 4.31 (2H, m), 6.67 (1H, m), 6.87 (1H, m), 6.95 (1H, m), 7.22 (2H, m), 7.39 (2H, m). | CC(C)S(=O)(=O)NC1Cc2ccc(-c3cccc(N)c3)cc2C1 | null | 81.4 | null |
173,972 | ord_dataset-3844acbccc714c04ab757ec4fca10bd0 | null | 1988-01-01T00:06:00 | true | [CH3:1][NH:2][N:3]1[C:12]2[C:7](=[CH:8][C:9]([F:15])=[C:10](F)[C:11]=2[F:13])[C:6](=[O:16])[C:5]([C:17]([OH:19])=[O:18])=[CH:4]1.[NH:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1.N1C=CC=CC=1.Cl>O>[CH3:1][NH:2][N:3]1[C:12]2[C:7](=[CH:8][C:9]([F:15])=[C:10]([N:20]3[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]3)[C:11]=2[F:13])[C:6](=[O:16])[C:5]([C:17]([OH:19])=[O:18])=[CH:4]1 | C1CNCCN1 | CNn1cc(C(=O)O)c(=O)c2cc(F)c(F)c(F)c21 | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | c1ccncc1 | null | null | null | null | null | null | null | null | null | null | null | A mixture of 1.95 g of 1-methylamino-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 3.05 g of anhydrous piperazine and 20 ml of dry pyridine is refluxed for 6 hours. The solvent is stripped off in vacuo, the residue is taken up in 20 ml of water, the pH is brought to 7-8 with half-concentrated hydrochloric acid, with cooling, and the precipitate is filtered off with suction, washed with ice-water and dried at 100° C. in vacuo. 1.8 g of 1-methylamino-6,8-difluoro-7-(1-piperazinyl)-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid of decomposition point 276°-278° C. are obtained. | CNn1cc(C(=O)O)c(=O)c2cc(F)c(N3CCNCC3)c(F)c21 | null | 74.3 | null |
1,764,477 | ord_dataset-0b32b90cc77b4a3db47ad263e0bbc1a8 | null | 2016-01-01T00:09:00 | true | [H-].[Na+].[CH3:3][N:4]([CH3:8])[CH2:5][CH2:6][OH:7].[CH2:9](Br)[CH:10]=[CH2:11]>CC(C)=O>[CH2:11]([O:7][CH2:6][CH2:5][N:4]([CH3:8])[CH3:3])[CH:10]=[CH2:9] | C=CCBr | CN(C)CCO | null | [H-] | [Na+] | 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 | 0 | 0.5 | Sodium hydride (17.5 g) and dimethyl formaldehyde (400 mL) were added to a 2-L round-bottom flask. After cooling the flask to 0° C. by immersing in an ice bath, 2-dimethylaminoethanol (0.398 mol) was added. After stirring for about 30 minutes and adding allyl bromide (0.4378 mol), the mixture was stirred for 3 hours after raising the temperature of the reactor to room temperature. Upon completion of reaction, the reaction was terminated by adding water to the flask and the product was extracted using diethyl ether. The extract was concentrated under reduced pressure and used in the next step without further purification. After filtration under reduced pressure, 2-(allyloxy)-N,N-dimethylethanamine was obtained through fractional distillation. Structural analysis was performed by NMR spectroscopy. | C=CCOCCN(C)C | null | null | null |
524,502 | ord_dataset-293186f5c9b441cab57f03cd3a18ac26 | null | 2001-01-01T00:11:00 | true | [C:1]([CH2:3]P(=O)(OCC)OCC)#[N:2].[H-].[Na+].[O:14]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:17](=O)[CH2:16][CH2:15]1>O1CCCC1>[O:14]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:17](=[CH:3][C:1]#[N:2])[CH2:16][CH2:15]1 | CCOP(=O)(CC#N)OCC | O=C1CCOc2ccccc21 | null | [H-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | 0 | 0.17 | Diethyl cyanomethylphosphonate (1.15 eq.) is slowly added to a suspension of sodium hydride (1.15 eq.) in anhydrous tetrahydrofuran at 0° C. The reaction medium is stirred for 10 minutes at 0° C. and then cooled to −78° C. 4-Chromanone dissolved in tetrahydrofuran is added. The temperature is then returned slowly to 20-25° C. over 2 hours 30. After removal of the solvent, the compounds are extracted with ethyl acetate. The organic phase is washed with a large amount of a saturated solution of sodium chloride, concentrated and purified (Z/E mixture) on a silica column (AcOEt/PE 3/7). | N#CC=C1CCOc2ccccc21 | null | null | null |
501,276 | ord_dataset-d673d02cdac14dba9ff59f12845a4f37 | null | 2001-01-01T00:05:00 | true | [CH2:1]([O:3][C:4]([CH2:6][CH2:7][CH2:8][O:9][C:10]1[CH:42]=[CH:41][C:13]([C:14]([NH:16][S:17]([C:20]2[C:25]([CH3:26])=[CH:24][C:23]([O:27][CH2:28][CH2:29][CH2:30][C:31]([O:33]CC(Cl)(Cl)Cl)=[O:32])=[C:22]([CH3:39])[C:21]=2[CH3:40])(=[O:19])=[O:18])=[NH:15])=[CH:12][CH:11]=1)=[O:5])[CH3:2].O>[Zn].CC(O)=O>[CH2:1]([O:3][C:4]([CH2:6][CH2:7][CH2:8][O:9][C:10]1[CH:42]=[CH:41][C:13]([C:14]([NH:16][S:17]([C:20]2[C:25]([CH3:26])=[CH:24][C:23]([O:27][CH2:28][CH2:29][CH2:30][C:31]([OH:33])=[O:32])=[C:22]([CH3:39])[C:21]=2[CH3:40])(=[O:19])=[O:18])=[NH:15])=[CH:12][CH:11]=1)=[O:5])[CH3:2] | CCOC(=O)CCCOc1ccc(C(=N)NS(=O)(=O)c2c(C)cc(OCCCC(=O)OCC(Cl)(Cl)Cl)c(C)c2C)cc1 | null | null | [Zn] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(=O)O | O | null | null | null | null | null | null | null | null | null | 25 | 3.25 | Zn powder (0.32 g) was added to a mixture of 4-ethoxycarbonylpropoxy-N-{4-[3-(2,2,2-trichloroethoxycarbonyl)propoxy]-2,3,6-trimethylbenzenesulfonyl}benzamidine (0.65 g), water (2 ml), and AcOH (18 ml) under ice-water cooling. The reaction mixture was stirred at room temperature for 3.25 hours, and then evaporated. The resulting precipitate was removed by filtration, and was washed with AcOEt and isopropyl ether (IPE). The filtrate, AcOEt, and IPE were combined, and then washed with water. The organic phase was dried over MgSO4, and evaporated. The resulting residue was purified by chromatography over silica gel (CHCl3-MeOH as eluent) to give 4-ethoxycarbonylpropoxy-N-[4-(3-carboxypropoxy)-2,3,6-trimethylbenzenesulfonyl]benzamidine (0.17 g) as an oil compound. | CCOC(=O)CCCOc1ccc(C(=N)NS(=O)(=O)c2c(C)cc(OCCCC(=O)O)c(C)c2C)cc1 | null | 32.6 | null |
1,729,056 | ord_dataset-36057d699ac5449e9c37eb99abf78b03 | null | 2016-01-01T00:05:00 | true | [F:1][C:2]([F:23])([F:22])[C:3]([N:5]([C@@H:13]1[CH2:15][C@H:14]1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:6][CH:7]1[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]1)=[O:4].C(=O)([O-])[O-].[K+].[K+].Br[CH2:31][CH2:32][OH:33]>C(#N)C>[F:23][C:2]([F:1])([F:22])[C:3]([N:5]([CH2:6][CH:7]1[CH2:8][CH2:9][N:10]([CH2:31][CH2:32][OH:33])[CH2:11][CH2:12]1)[C@@H:13]1[CH2:15][C@H:14]1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:4] | O=C(N(CC1CCNCC1)[C@@H]1C[C@H]1c1ccccc1)C(F)(F)F | OCCBr | 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 | 80 | null | To the solution of 2,2,2-trifluoro-N-(trans-2-phenylcyclopropyl)-N-(piperidin-4-ylmethyl)acetamide (60 mg, 0.184 mmol) in acetonitrile (10 mL) was added potassium carbonate (76 mg, 0.552 mmol) followed by 2-bromoethanol (29.9 mg, 0.239 mmol). The reaction mixture was heated in the seal tube at 80° C. for 4 hours. The reaction mixture was then filtered and evaporated. 2,2,2-Trifluoro-N-((1-(2-hydroxyethyl)piperidin-4-yl)methyl)-N-(trans-2-phenylcyclopropyl)acetamide (40 mg, 0.103 mmol, 55.8% yield) was isolated as yellow oil. 1H NMR (400 MHz, METHANOL-d4) δ 7.07-7.37 (m, 5H), 3.75-3.87 (m, 2H), 3.57-3.66 (m, 1H), 3.49-3.57 (m, 1H), 3.46 (t, J=6.06 Hz, 1H), 3.36-3.41 (m, 3H), 3.19 (t, J=3.79 Hz, 1H), 2.78-3.04 (m, 2H), 2.56-2.76 (m, 1H), 2.48 (ddd, J=3.54, 6.51, 10.17 Hz, 1H), 1.96-2.15 (m, 1H), 1.87 (td, J=2.91, 10.80 Hz, 2H), 1.63 (dt, J=5.24, 10.23 Hz, 1H), 1.39-1.57 (m, 3H); LC-MS Rt=0.76 min; MS (ESI): 371.2 [M+H]+. | O=C(N(CC1CCN(CCO)CC1)[C@@H]1C[C@H]1c1ccccc1)C(F)(F)F | null | 56 | null |
1,556,471 | ord_dataset-4e54080057a44c3887653391e24c90b6 | null | 2015-01-01T00:03:00 | true | [C:1]1([N:7]2[C:11]([NH:12][C:13](=[O:21])OC3C=CC=CC=3)=[CH:10][C:9]([C:22]([F:25])([F:24])[F:23])=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:26][O:27][C:28]1[CH:29]=[C:30]2[C:35](=[CH:36][C:37]=1[O:38][CH3:39])[N:34]=[CH:33][N:32]=[C:31]2[O:40][C:41]1[CH:42]=[C:43]([CH:45]=[CH:46][CH:47]=1)[NH2:44].C(N(CC)C(C)C)(C)C>C1COCC1>[CH3:26][O:27][C:28]1[CH:29]=[C:30]2[C:35](=[CH:36][C:37]=1[O:38][CH3:39])[N:34]=[CH:33][N:32]=[C:31]2[O:40][C:41]1[CH:42]=[C:43]([NH:44][C:13]([NH:12][C:11]2[N:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[N:8]=[C:9]([C:22]([F:23])([F:24])[F:25])[CH:10]=2)=[O:21])[CH:45]=[CH:46][CH:47]=1 | O=C(Nc1cc(C(F)(F)F)nn1-c1ccccc1)Oc1ccccc1 | COc1cc2ncnc(Oc3cccc(N)c3)c2cc1OC | 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 | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | null | The title compound was prepared as described in Example 159B, using phenyl 1-phenyl-3-(trifluoromethyl)-1H-pyrazol-5-ylcarbamate from the previous step (0.139 g, 0.4 mmol), 3-(6,7-dimethoxyquinazolin-4-yloxy)aniline from Example 113A (0.119 g, 0.4 mmol), and N,N-diisopropylethylamine (0.3 mL) in THF (6 mL) at 50° C. for 6 hours, to afford 1-[3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl]-3-[1-phenyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]urea as solid (0.116 g, 53%). 1H NMR (300 MHz, DMSO-d6) δ 9.32 (s, 1H), 8.80 (s, 1H), 8.55 (s, 1H), 7.54-7.62 (m, 7H), 7.39 (m, 2H), 7.19 (d, 1H), 6.96 (d, 1H), 6.86 (s, 1H), 3.99 (s, 3H), 3.98 (s, 3H); LC-MS (ESI) m/z 551 (M+H)+. | COc1cc2ncnc(Oc3cccc(NC(=O)Nc4cc(C(F)(F)F)nn4-c4ccccc4)c3)c2cc1OC | null | 53 | null |
1,625,310 | ord_dataset-35c51552812941cda45194a013d34bb9 | null | 2015-01-01T00:08:00 | true | [NH:1]1[C:9]2[CH2:8][CH2:7][CH2:6][CH2:5][C:4]=2[CH:3]=[C:2]1[C:10]([O:12][CH2:13][CH3:14])=[O:11].[H-].[Na+].Br[CH2:18][C:19]#[N:20]>CN(C=O)C>[C:19]([CH2:18][N:1]1[C:9]2[CH2:8][CH2:7][CH2:6][CH2:5][C:4]=2[CH:3]=[C:2]1[C:10]([O:12][CH2:13][CH3:14])=[O:11])#[N:20] | N#CCBr | CCOC(=O)c1cc2c([nH]1)CCCC2 | null | [H-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | 0 | 1 | A 125-mL single-neck round-bottomed flask equipped with a magnetic stirrer and nitrogen inlet was purged with nitrogen and charged with ethyl 4,5,6,7-tetrahydro-1H-indole-2-carboxylate 104g (5.76 g, 29.8 mmol) and DMF (50 mL). The solution was cooled to 0° C. using an ice bath. Sodium hydride, NaH (60% dispersion in mineral oil, 1.43 g, 35.8 mmol) was added. The resulting mixture was stirred at room temperature for 1 h. After that time, bromoacetonitrile (1.43 g, 35.8 mmol) was added. The mixture was stirred at room temperature for 14 h. After that time, the reaction mixture was concentrated under reduced pressure and the residue was partitioned between ethyl acetate (150 mL) and water (450 mL). The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (3×150 mL). The combined organic layers were washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography to afford a 55% yield (3.80 g) of 104h as a yellow semi-solid: 1H NMR (300 MHz, CDCl3) δ 6.66 (s, 1H), 5.29 (s, 2H), 4.28 (q, 2H, J=7.2 Hz), 2.62 (t, 2H, J=6.3 Hz), 2.49 (t, 2H, J=6.3 Hz), 1.92 (m, 2H), 1.75 (m, 2H), 1.33 (t, 3H, J=7.2 Hz); MS (ESI+) m/z 233.1 (M+H) | CCOC(=O)c1cc2c(n1CC#N)CCCC2 | null | 54.9 | null |
330,167 | ord_dataset-2c460e2ef9934444aaf26fec1f75741f | null | 1996-01-01T00:05:00 | true | [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1([CH:11]2[C:20]3[C:15](=[CH:16][C:17]([F:23])=[C:18]([O:21]C)[CH:19]=3)[CH2:14][CH2:13][N:12]2[CH3:24])[CH2:10][CH2:9]1.[BrH:25]>C(O)(=O)C>[BrH:25].[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1([CH:11]2[C:20]3[C:15](=[CH:16][C:17]([F:23])=[C:18]([OH:21])[CH:19]=3)[CH2:14][CH2:13][N:12]2[CH3:24])[CH2:10][CH2:9]1 | COc1cc2c(cc1F)CCN(C)C2C1(c2ccccc2Cl)CC1 | null | null | Br | 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 | null | null | A mixture of 1-[1-(2-chlorophenyl)cyclopropyl]-6-fluoro-7-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline (18.0 g) in acetic acid (150 ml) and 48% aqueous hydrobromic acid (150 ml) was heated under reflux under argon for 220 minutes. The solvent was removed in vacuo, and the residue dried by azeotropic distillation with propan-2-ol and crystallised from propan-2-ol to yield 1-[1-(2-chlorophenyl)cyclopropyl]-6-fluoro-7-hydroxy-2-methyl-1,2,3,4-tetrahydroisoquinoline hydrobromide (18.56 g), m.p. 240° C. (dec). | CN1CCc2cc(F)c(O)cc2C1C1(c2ccccc2Cl)CC1 | null | null | null |
511,967 | ord_dataset-85c00026681b46f89ef8634d2b8618c3 | null | 2001-01-01T00:07:00 | true | [C:1]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[H-].[Na+].Cl[C:15]1[CH:20]=[CH:19][C:18]([C:21]#[N:22])=[CH:17][C:16]=1[N+:23]([O-:25])=[O:24].Cl>CN(C=O)C>[C:21]([C:18]1[CH:19]=[CH:20][C:15]([CH:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])[C:1]([O:9][CH2:10][CH3:11])=[O:8])=[C:16]([N+:23]([O-:25])=[O:24])[CH:17]=1)#[N:22] | N#Cc1ccc(Cl)c([N+](=O)[O-])c1 | CCOC(=O)CC(=O)OCC | null | Cl | [H-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | 25 | 0.5 | Diethyl malonate (44.6ml, 293 mmol) was added dropwise over 1.5 hours to a suspension of sodium hydride (11.7 g of a 60% suspension in mineral oil, 293 mmol) in DMF under argon and the reaction mixture was stirred at ambient temperature for 30 minutes. The resulting solution was added dropwise over 1 hour to a solution of 2-chloro-5-cyano-1-nitrobenzene (24.3 g, 133 mmol) in DMF (75 ml) cooled with a dry ice/acetone bath. The temperature of the cooling bath was adjusted to prevent the freezing of the red reaction mixture. After the addition was completed, the reaction was left to rise to ambient temperature over 2 hours. The resulting red solution was poured slowly into a stirred mixture of ice (100 ml) and 1M hydrochloric acid (10 ml). The resulting yellow precipitate was collected by filtration, washed with water until the filtrate was at pH7.0 and then dried under vacuum to give diethyl (4-cyano-2-nitrophenyl)malonate (39.6 g, 97%). | CCOC(=O)C(C(=O)OCC)c1ccc(C#N)cc1[N+](=O)[O-] | null | 97.2 | null |
1,176,505 | ord_dataset-0f9d2dbe929a45c3892ae75e81e99443 | null | 2012-01-01T00:06:00 | true | [NH2:1][C:2]1[CH:20]=[CH:19][C:5]([O:6][C:7]2[C:16]3[N:15]=[C:14]([CH3:17])[C:13](=[O:18])[NH:12][C:11]=3[N:10]=[CH:9][CH:8]=2)=[CH:4][C:3]=1[S:21][CH3:22].[C:23]([C:27]1[CH:31]=[C:30]([N:32]=[C:33]=[O:34])[N:29]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[N:28]=1)([CH3:26])([CH3:25])[CH3:24]>>[C:23]([C:27]1[CH:31]=[C:30]([NH:32][C:33]([NH:1][C:2]2[CH:20]=[CH:19][C:5]([O:6][C:7]3[C:16]4[N:15]=[C:14]([CH3:17])[C:13](=[O:18])[NH:12][C:11]=4[N:10]=[CH:9][CH:8]=3)=[CH:4][C:3]=2[S:21][CH3:22])=[O:34])[N:29]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[N:28]=1)([CH3:26])([CH3:24])[CH3:25] | CC(C)(C)c1cc(N=C=O)n(-c2ccccc2)n1 | CSc1cc(Oc2ccnc3[nH]c(=O)c(C)nc23)ccc1N | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Method F2 was used with 8-(4-amino-3-(methylthio)phenoxy)-2-methylpyrido[2,3-b]pyrazin-3(4H)-one and 3-tert-butyl-5-isocyanato-1-phenyl-1H-pyrazole to afford the title compound (45 mg, 51%) as a white solid. | CSc1cc(Oc2ccnc3[nH]c(=O)c(C)nc23)ccc1NC(=O)Nc1cc(C(C)(C)C)nn1-c1ccccc1 | null | 51 | null |
801,483 | ord_dataset-56a22bc0c3b14f87b9aa3f2fc6488ee7 | null | 2007-01-01T00:12:00 | true | CC12C3(C)[N:6]4[CH2:7][CH2:8][CH2:9][N:10]3[CH2:11][CH2:12][N:13]1[CH2:14][CH:15]([C:17]([O:19]C)=[O:18])[CH2:16][N:3]2[CH2:4][CH2:5]4.Cl>C(O)C>[NH:6]1[CH2:7][CH2:8][CH2:9][NH:10][CH2:11][CH2:12][NH:13][CH2:14][CH:15]([C:17]([OH:19])=[O:18])[CH2:16][NH:3][CH2:4][CH2:5]1 | COC(=O)C1CN2CCN3CCCN4CCN(C1)C2(C)C34C | null | 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 | 0 | null | A solution of 0.50 g (1.62 mmol) of compound 3, prepared in example A, stage (b), in 20 ml of absolute ethanol is brought to reflux. 3 ml of a 35% aqueous hydrochloric acid solution are added in small amounts. Reflux is maintained for 48 hours. The mixture is cooled to 0° C. and the precipitate formed is filtered off and washed with ice-cold ethanol. The filtrate is evaporated and then the residue is taken up in the minimum amount of ethanol. The precipitate formed is filtered off and washed with ice-cold ethanol. Compound 6·3HCl is isolated in the form of a white powder (0.57 g, Yield =92%). Overall yield starting from the tetraamine: 87%. | O=C(O)C1CNCCNCCCNCCNC1 | null | null | null |
1,302,969 | ord_dataset-78c3f723155a4347a902b53bcee1524d | null | 2013-01-01T00:06:00 | true | C([O:3][C:4]([C@H:6]1[CH2:11][CH2:10][C@H:9]([O:12][C:13]2[CH:18]=[CH:17][N:16]=[CH:15][N:14]=2)[CH2:8][CH2:7]1)=[O:5])C.[OH-].[Na+]>O1CCOCC1>[N:16]1[CH:17]=[CH:18][C:13]([O:12][C@H:9]2[CH2:8][CH2:7][C@H:6]([C:4]([OH:5])=[O:3])[CH2:11][CH2:10]2)=[N:14][CH:15]=1 | CCOC(=O)[C@H]1CC[C@H](Oc2ccncn2)CC1 | null | null | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1COCCO1 | null | null | null | null | null | null | null | null | null | null | 25 | 3 | To a solution of cis/trans-4-(pyrimidin-4-yloxy)-cyclohexanecarboxylic acid ethyl ester (1:1) (0.90 g, 3.6 mmol) in 1,4-dioxane (18 ml) was added 2 M aqueous sodium hydroxide solution (18 ml, 36 mmol). Stirring at room temperature for 3 h was followed by acidification to pH 2-3 with 1 M aqueous hydrogen chloride solution (42 ml) and extraction with four 100-ml portions of ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo to give the title compound (0.76 g, 95%) as white solid. | O=C(O)[C@H]1CC[C@H](Oc2ccncn2)CC1 | null | null | null |
700,131 | ord_dataset-bbd7e53f000345838ad4920a07a169ff | null | 2006-01-01T00:03:00 | true | [Cl:1][C:2]1[C:10]2[CH2:11][CH2:12][N:13](C)[CH2:14][CH2:15][N:8]3[C:9]=2[C:5]([C:6]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][C:7]=23)=[CH:4][CH:3]=1.ClC(OC(Cl)C)=O>ClC(Cl)C>[Cl:1][C:2]1[C:10]2[CH2:11][CH2:12][NH:13][CH2:14][CH2:15][N:8]3[C:9]=2[C:5]([C:6]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][C:7]=23)=[CH:4][CH:3]=1 | CN1CCc2c(Cl)ccc3c4c(n(c23)CC1)CCCCC4 | null | null | CC(Cl)OC(=O)Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(Cl)Cl | null | null | null | null | null | null | null | null | null | null | 25 | null | To a solution of 6-chloro-3-methyl-2,3,4,5,10,11,12,13-octahydro-1H,9H-cyclohepta[b][1,4]diazocino[7,8,1-hi]indole (0.30 g, 0.99 mmole) in dichloroethane (80 mL) was added 1-chloroethyl chloroformate (1.2 mL, 10.8 mmole) and the mixture refluxed for 24 hours. The reaction mixture was cooled to room temperature and the solvent removed in vacuo and replaced with methanol (25 mL) and refluxed for another 3 hours. The reaction mixture was then cooled to room temperature and the solvent removed in vacuo. The dark residue was dissolved in methylene chloride (200 mL) and washed with aqueous sodium hydroxide (1N, 150 mL), saturated sodium chloride (150 mL), dried (sodium sulfate) and concentrated. Purification by flash column chromatography (silica gel, 1.5% methanol in dichloromethane) provided 0.28 g of the title compound. 88 mg of this was further treated with one equivalent of fumaric acid in ethanol to form a fumarate salt, mp 208-210° C. MS (ESI) m/z 289 ([M+H]+). | Clc1ccc2c3c(n4c2c1CCNCC4)CCCCC3 | null | 97.9 | null |
1,199,211 | ord_dataset-fb72428f30234761b4216139dc228d0c | null | 2012-01-01T00:09:00 | true | [CH2:1]([Mg]Br)[CH2:2][CH2:3][CH:4]=[CH2:5].[CH2:8](O)[CH2:9][CH2:10][CH2:11][CH2:12]O>>[CH2:5]=[CH:4][CH2:3][CH2:2][CH2:1][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:5][CH2:4][CH2:3][CH:2]=[CH2:1] | OCCCCCO | C=CCCC[Mg]Br | null | null | null | null | null | null | null | 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 copper catalyzed coupling reaction of a Grignard reagent with an organic halide, which is commonly referred to as a halide displacement reaction, was first reported in 1971 by Kochi and Tamura (J. Am. Chem. Soc. 1971, 93, 1487, Synthesis 1971, 303, J. Organomet. Chem. 1972, 42, 205). In the Synthesis paper the authors reported the coupling reaction of n-butylmagnesium bromide with n-hexyl bromide in the presence of dilithiumtetrachlorocuprate (Li2CuCl4). Since that report the use of Li2CuCl4 in coupling reactions has been quite extensive and is prominent in the synthesis of pheromones as well as in the synthesis of α,ω-olefins. One of the more interesting uses of this copper catalyzed coupling reaction may be found in U.S. Pat. No. 4,912,253 where sorbyl acetate was coupled with the Grignard prepared from the magnesium salt of chlorohexanol to form the codling moth (Laspeyresia pomonella) sex pheromone 8,10-dodecadien-1-ol on a metric ton scale. α,ω-olefins have been formed by coupling 4-pentenylmagnesium bromide with the bis-tosylate of 1,5-pentanediol to form 1,14-pentadecadiene in 81% yield (Tetrahedron 1991, 47, 6287-6292). 1,9-Decadiene has been prepared by the Li2CuCl4 catalyzed coupling reaction of 1,4-dibromobutane with allylmagnesium bromide at 25° C. in 38% yield (Synthetic Communications 1994, 24, 459-463). | C=CCCCCCCCCCCCC=C | null | 81 | null |
134,543 | ord_dataset-b76b52f4448a4eedb28ffcd8f902046a | null | 1985-01-01T00:09:00 | true | Cl[C:2]1[N:7]=[C:6]([O:8][CH3:9])[N:5]=[C:4]([O:10][CH3:11])[C:3]=1[S:12][CH3:13].[CH3:14][OH:15].[OH-].[K+]>O>[CH3:13][S:12][C:3]1[C:4]([O:10][CH3:11])=[N:5][C:6]([O:8][CH3:9])=[N:7][C:2]=1[O:15][CH3:14] | COc1nc(Cl)c(SC)c(OC)n1 | CO | null | [K+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | null | null | null | null | null | null | null | null | null | null | null | null | Charged into a 100-milliliter, 4-necked flask equipped with a reflux condenser, thermometer and stirrer were 2.2 g of 6-chloro-2,4-dimethoxy-5-methylthiopyrimidine and 40 ml of methanol. They were stirred into a homogeneous solution. Subsequent to an addition of 2.0 g of potassium hydroxide, the resultant mixture was heated and refluxed, with thorough stirring, for 3 hours. The liquid reaction mixture was then poured into water and the resultant solid precipitate was collected by filtration. It was recrystallized from isopropyl alcohol, thereby obtaining 5-methylthio-2,4,6-trimethoxypyrimidine (m.p. 90°-91° C.). Yield: 1.96 g(90.7%). | COc1nc(OC)c(SC)c(OC)n1 | null | null | null |
1,282,610 | ord_dataset-d5c54236ecd94d61aaa071461bcfc426 | null | 2013-01-01T00:04:00 | true | [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]2([CH2:13][O:12][C:11]3=[CH:14][C:15]4[CH2:19][CH2:18][O:17][C:16]=4[CH:20]=[C:10]23)[C:2]1=[O:21].Br.Br[CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=1.BrCC1CCCCO1>>[N:26]1[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=1[CH2:24][N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]2([CH2:13][O:12][C:11]3=[CH:14][C:15]4[CH2:19][CH2:18][O:17][C:16]=4[CH:20]=[C:10]23)[C:2]1=[O:21] | O=C1Nc2ccccc2C12COc1cc3c(cc12)OCC3 | BrCc1ccccn1 | null | Br | BrCC1CCCCO1 | null | null | null | null | 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 as described in EXAMPLE 4 and making non-critical variations using 6,7-dihydrospiro[benzo[1,2-b:4,5-b′]difuran-3,3′-indol]-2′(1′H)-one to replace 5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-2″(1′H)-one, and 2-(bromomethyl)pyridine hydrobromide to replace 2-(bromomethyl)tetrahydro-2H-pyran, 1′-(pyridin-2-ylmethyl)-6,7-dihydrospiro[benzo[1,2-b:4,5-b′]difuran-3,3′-indol]-2′(1′H)-one was obtained (67%) as a colorless solid: mp 198-200° C. (diethyl ether/hexanes); 1H NMR (300 MHz, CDCl3) δ8.59 (d, J=4.8 Hz, 1H), 7.71 (dd, J=7.8, 7.5 Hz, 1H), 7.32-7.15 (m, 4H), 7.02 (dd, J=7.5, 7.5 Hz, 1H), 6.94 (d, J=7.8 Hz, 1H), 6.82 (s, 1H), 6.17 (s, 1H), 5.27 (d, J=15.6 Hz, 1H), 5.01 (d, J=15.6 Hz, 1H), 4.98 (d, J=9.0 Hz, 1H), 4.70 (d, J=9.0 Hz, 1H), 4.49 (td, J=8.7, 0.7 Hz, 2H), 3.15 (t, J=8.7 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ177.7, 155.3, 155.2, 154.9, 148.6, 142.1, 138.3, 132.1, 129.1, 128.9, 127.6, 124.0, 123.7, 123.3, 122.3, 109.7, 107.2, 104.0, 80.1, 71.8, 58.6, 45.5, 30.4; MS (ES+) m/z 370.9 (M+1). | O=C1N(Cc2ccccn2)c2ccccc2C12COc1cc3c(cc12)OCC3 | null | null | null |
16,039 | ord_dataset-b971427c0b944c56b63bb2356fa8ca69 | null | 1976-01-01T00:11:00 | true | [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][C:9]#N)=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12].CN(C)C=O.[BH4-].[Na+].[Br:21][CH2:22][CH2:23]CBr>O>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH2:9][CH2:23][CH2:22][Br:21])=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12] | N#CSc1ccc(N)c([N+](=O)[O-])c1 | BrCCCBr | null | [BH4-] | [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 | 1 | 5.85 G. of 1-amino-2-nitro-4-thiocyanatobenzene in 20 ml. dimethylformamide is treated under nitrogen with 1.14 g. sodium borohydride at not greater than 30°. The mixture is stirred for one hour at 15°-20°, then treated with 12 g. of 1,3-dibromopropane at 20°-25°. After a further 3 hours, water is added and the crude product extracted with chloroform. The dried chloroform solution is passed through a column of silica gel to remove polar material. Pure 1-amino-2-nitro-4-(3-bromopropylthio)benzene is obtained from the eluate. | Nc1ccc(SCCCBr)cc1[N+](=O)[O-] | null | null | null |
1,749,770 | ord_dataset-60a3e71da3174666a50a61dcfa611a9f | null | 2016-01-01T00:07:00 | true | Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([Cl:12])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.[F:13][C:14]1[C:19]([CH3:20])=[CH:18][C:17](B2OC(C)(C)C(C)(C)O2)=[CH:16][C:15]=1[CH3:30].C(=O)([O-])[O-].[Na+].[Na+].C(COC)OC>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>[Cl:12][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([C:17]3[CH:18]=[C:19]([CH3:20])[C:14]([F:13])=[C:15]([CH3:30])[CH:16]=3)=[N:3][CH:4]=[N:5]2)=[CH:10][CH:9]=1 | Clc1ccc2c(Cl)ncnc2c1 | Cc1cc(B2OC(C)(C)C(C)(C)O2)cc(C)c1F | null | c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1 | O=C([O-])[O-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | COCCOC | O | null | null | null | null | null | null | null | null | null | null | null | 4,7-dichloroquinazoline (4.0 g, 20.1 mmol), 2-(4-fluoro-3,5-dimethylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (5.53 g, 22.1 mmol), sodium carbonate (5.33 g, 50.2 mmol), palladium tetrakis (0.70 g, 0.60 mmol), dimethoxyethane (“DME”) (160 mL), and water (40 mL) were combined in a three neck round bottom flask. A condenser was attached then the system was evacuated and purged with nitrogen three times. The reaction was heated to a vigorous reflux overnight. The reaction was diluted with ethyl acetate, water and brine. The aqueous was partitioned off and the organic was washed once with brine, dried with sodium sulfate, filtered then concentrated down to a yellow solid. The yellow solid was purified with silica gel using DCM to 85/15 DCM/ethyl acetate solvent system to get 4.1 g of light yellow solid for a 71% yield. | Cc1cc(-c2ncnc3cc(Cl)ccc23)cc(C)c1F | null | 71.1 | null |
849,527 | ord_dataset-171b840ae6e84e45bab43b987d09f5c7 | null | 2008-01-01T00:11:00 | true | Cl.Cl.[CH2:3]([O:5][CH2:6][C@:7]1([C:13]([N:15]2[CH2:20][CH2:19][N:18]([C:21]3[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[CH:23][N:22]=3)[CH2:17][CH2:16]2)=[O:14])[CH2:11][CH2:10][C@@H:9]([NH2:12])[CH2:8]1)[CH3:4].[CH3:31][CH:32]1[C:37](=O)[CH2:36][CH2:35][O:34][CH2:33]1.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[CH2:3]([O:5][CH2:6][C@:7]1([C:13]([N:15]2[CH2:16][CH2:17][N:18]([C:21]3[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[CH:23][N:22]=3)[CH2:19][CH2:20]2)=[O:14])[CH2:11][CH2:10][C@@H:9]([NH:12][C@@H:37]2[CH2:36][CH2:35][O:34][CH2:33][CH:32]2[CH3:31])[CH2:8]1)[CH3:4] | CCOC[C@]1(C(=O)N2CCN(c3cc(C(F)(F)F)ccn3)CC2)CC[C@@H](N)C1 | CC1COCCC1=O | null | CC(=O)O[BH-](OC(C)=O)OC(C)=O | Cl | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | CCN(CC)CC | null | null | null | null | null | null | null | null | null | 25 | 8 | To a solution of (1R,3S)-3-(ethoxymethyl)-3-(4-[4-(trifluoromethyl)pyridin-2-yl]piperazin-1-ylcarbonyl)cyclopentanamine dihydrochloride (100.0 mg, 0.211 mmol), 3-methyltetrahydro-4H-pyran-4-one (72.3 mg, 0.634 mmol) and triethylamine (0.118 mL, 0.845 mmol) in dry methylene chloride (5 mL) was added sodium triacetoxyborohydride (134.3 mg, 0.634 mmol). After being stirred at room temperature under N2 overnight, the reaction was quenched with aqueous NaHCO3 and diluted with methylene chloride. The organic layer was separated and the aqueous layer was extracted with methylene chloride three times. The organics were combined, dried over MgSO4, filtered, purified by silica gel Combi-Flash system (gradient, 0 to 40% MeOH in EtOAc, 12 gram column) to give the desired product (34 mg, 34%). MS calculated for C25H37F3N4O3: (M+H) 499.3; found 499.3. | CCOC[C@]1(C(=O)N2CCN(c3cc(C(F)(F)F)ccn3)CC2)CC[C@@H](N[C@@H]2CCOCC2C)C1 | null | 32.3 | null |
1,038,734 | ord_dataset-3af92aec23dc4810b92eb0d8c60023ee | null | 2011-01-01T00:03:00 | true | [NH2:1][C:2]1[S:6][C:5]([C:7]2[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH3:14].[C:15]([O:19][C:20]([N:22]1[CH2:30][CH2:29][CH2:28][CH:24]([C:25](O)=[O:26])[CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16]>>[C:15]([O:19][C:20]([N:22]1[CH2:30][CH2:29][CH2:28][CH:24]([C:25]([NH:1][C:2]2[S:6][C:5]([C:7]3[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][CH:8]=3)=[N:4][C:3]=2[CH3:14])=[O:26])[CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16] | CC(C)(C)OC(=O)N1CCCC(C(=O)O)C1 | Cc1nc(-c2ccc(Cl)cc2)sc1N | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Using 5-amino-2-(4-chlorophenyl)-4-methylthiazole (197 mg, 0.877 mmol) and 1-(tert-butoxycarbonyl)nipecotic acid (205 mg, 0.877 mmol), the same procedure was followed as in Step 3a of Example 3 to give 115 mg (30%) of the desired compound as a yellow powder. | Cc1nc(-c2ccc(Cl)cc2)sc1NC(=O)C1CCCN(C(=O)OC(C)(C)C)C1 | null | 30.1 | null |
1,207,252 | ord_dataset-fb72428f30234761b4216139dc228d0c | null | 2012-01-01T00:09:00 | true | C([O:5][C:6](=[O:18])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][C:10]=1[C:16]#[CH:17])(C)(C)C.Cl.O1CCOCC1>C(Cl)Cl>[Cl:15][C:12]1[CH:13]=[CH:14][C:9]([O:8][CH2:7][C:6]([OH:18])=[O:5])=[C:10]([C:16]#[CH:17])[CH:11]=1 | C#Cc1cc(Cl)ccc1OCC(=O)OC(C)(C)C | null | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | C1COCCO1 | null | null | null | null | null | null | null | null | null | null | 8 | A solution of (4-chloro-2-ethynyl-phenoxy)-acetic acid tert-butyl ester (Intermediate 3; 500 mg; 1.87 mmol) in DCM (2.5 ml) was treated with a 4 N solution of HCl in dioxane (14 ml; 56 mmol) and stirred overnight. The solvents were removed under reduced pressure, to give the title compound. | C#Cc1cc(Cl)ccc1OCC(=O)O | null | null | null |
419,001 | ord_dataset-94e21e9990034c729ea727e7d2ab0eb0 | null | 1998-01-01T00:12:00 | true | S(=O)(=O)(O)O.[CH3:6][O:7][C:8]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:9]=1C=O.OO.S([O-])(O)=[O:21].[K+]>CO>[CH3:6][O:7][C:8]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:9]=1[OH:21] | COc1ccc(C=O)c(OC)c1 | O=S([O-])O | null | O=S(=O)(O)O | OO | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | 25 | 4 | Conc. sulfuric acid (0.4 ml) was added to a mixed solution comprising 3.3 g of 2,4-dimethoxybenzaldehyde and 30 ml of methanol, and under ice-cooling, 2.93 ml of 30% hydrogen peroxide aqueous solution was added to the mixture. After stirring at room temperature for 4 hours, a 5% aqueous potassium hydrogen sulfite solution was added to the mixture and the solvent was removed under reduced pressure. The residue was extracted with diethyl ether, the extract was washed and dried and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (solvent; hexane:ethyl acetate=4:1) to give 2.1 g of 2,4-dimethoxyphenol (yield: 69%, state: colorless oily product). | COc1ccc(O)c(OC)c1 | null | 69 | null |
679,615 | ord_dataset-3947f3e1be17462c8f7c7e6ea6e57d0a | null | 2005-01-01T00:08:00 | true | [CH2:1]([C:3]1([C:8]2[CH:13]=[CH:12][C:11]([C:14]3[C:19]([CH3:20])=[CH:18][CH:17]=[C:16]([CH2:21][CH2:22][C:23]4[CH:28]=[CH:27][C:26]([CH2:29][OH:30])=[C:25]([CH2:31][OH:32])[CH:24]=4)[CH:15]=3)=[C:10]([CH2:33][CH2:34][CH3:35])[CH:9]=2)OCC[O:4]1)[CH3:2].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)([O-])O.[Na+]>CC(C)=O>[OH:32][CH2:31][C:25]1[CH:24]=[C:23]([CH2:22][CH2:21][C:16]2[CH:17]=[CH:18][C:19]([CH3:20])=[C:14]([C:11]3[CH:12]=[CH:13][C:8]([C:3](=[O:4])[CH2:1][CH3:2])=[CH:9][C:10]=3[CH2:33][CH2:34][CH3:35])[CH:15]=2)[CH:28]=[CH:27][C:26]=1[CH2:29][OH:30] | CCCc1cc(C2(CC)OCCO2)ccc1-c1cc(CCc2ccc(CO)c(CO)c2)ccc1C | null | null | Cc1ccc(S(=O)(=O)O)cc1 | O=C([O-])O | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CC(C)=O | null | null | null | null | null | null | null | null | null | null | null | 640 mg (1.4 mmol) of (4-{2-[4′-(2-ethyl[1,3]dioxolan-2-yl)-6-methyl-2′-propylbiphenyl-3-yl]ethyl}-2-hydroxymethylphenyl)methanol are placed in 15 ml of acetone and 15 ml of water in a round-bottomed flask. A spatula-tip of p-toluenesulfonic acid is added and the solution is refluxed for 2 hours 30 minutes. At room temperature, it is poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The organic phase is dried over magnesium sulfate, filtered and then evaporated. The residue obtained is purified by chromatography on a column of silica eluted with a mixture of heptane and ethyl acetate (30/70). 300 mg (50%) of the expected product are obtained in the form of a colorless oil. | CCCc1cc(C(=O)CC)ccc1-c1cc(CCc2ccc(CO)c(CO)c2)ccc1C | null | 49.8 | null |
1,618,419 | ord_dataset-35c51552812941cda45194a013d34bb9 | null | 2015-01-01T00:08:00 | true | [Cl:1][C:2]1[C:10]([O:11][CH3:12])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.[F:13][CH:14]([F:31])[C:15]1[N:20]=[CH:19][C:18]([C:21]2([CH2:29][NH2:30])[CH2:26][CH2:25][C:24]([F:28])([F:27])[CH2:23][CH2:22]2)=[CH:17][N:16]=1>>[Cl:1][C:2]1[C:10]([O:11][CH3:12])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([NH:30][CH2:29][C:21]1([C:18]2[CH:17]=[N:16][C:15]([CH:14]([F:31])[F:13])=[N:20][CH:19]=2)[CH2:26][CH2:25][C:24]([F:27])([F:28])[CH2:23][CH2:22]1)=[O:6] | COc1cccc(C(=O)O)c1Cl | NCC1(c2cnc(C(F)F)nc2)CCC(F)(F)CC1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | From 2-chloro-3-methoxybenzoic acid and (1-(2-(difluoromethyl)pyrimidin-5-yl)-4,4-difluorocyclohexyl)methanamine. LCMS (MH+): m/z=446.1, tR (minutes, Method F)=2.82 | COc1cccc(C(=O)NCC2(c3cnc(C(F)F)nc3)CCC(F)(F)CC2)c1Cl | null | null | null |
129,727 | ord_dataset-2f37329a4b254471a74f2eb0981f11ec | null | 1985-01-01T00:05:00 | true | [Cl:1][C:2]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[CH:17][C:3]=1[O:4][C:5]1[CH:6]=[CH:7][C:8]([N+:14]([O-:16])=[O:15])=[C:9]([CH:13]=1)[C:10](Cl)=[O:11].C(N(CC)CC)C.[OH:32][C:33]1[CH:34]=[N:35][CH:36]=[CH:37][CH:38]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[CH:17][C:3]=1[O:4][C:5]1[CH:6]=[CH:7][C:8]([N+:14]([O-:16])=[O:15])=[C:9]([CH:13]=1)[C:10]([O:32][C:33]1[CH:34]=[N:35][CH:36]=[CH:37][CH:38]=1)=[O:11] | Oc1cccnc1 | O=C(Cl)c1cc(Oc2ccc(C(F)(F)F)cc2Cl)ccc1[N+](=O)[O-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Cc1ccccc1 | CCN(CC)CC | null | null | null | null | null | null | null | null | null | 25 | null | To a stirred solution of 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitrobenzoyl chloride (3.79 g, 0.01 mole) and triethyl amine (1.01 g, 0.01 mole) in toluene (50 ml) was added 3-hydroxypyridine (0.95 g, 0.01 mole). The temperature exothermed to 33° C. and there was an immediate precipitate. The reaction was then refluxed for 24 hours, cooled to room temperature and the triethylamine hydrochloride precipitate collected by filtration. The toluene solution was washed with dilute sodium hydroxide solution and then with saturated sodium chloride solution. After drying and evaporation of the solvent there was obtained 3.1 g of brown oil which solidified. This was triturated with hexane and the solid filtered and dried to give a tan product, m.p. 65°-68° C. | O=C(Oc1cccnc1)c1cc(Oc2ccc(C(F)(F)F)cc2Cl)ccc1[N+](=O)[O-] | null | 70.7 | null |
945,979 | ord_dataset-ed680843f6d14f5c9901869b2a06b4a4 | null | 2010-01-01T00:03:00 | true | Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([F:15])([F:14])[F:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].[C:22]1([OH:28])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>C(#N)C>[O:28]([C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([F:15])([F:14])[F:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1 | FC(F)(F)c1ccc2ncnc(Cl)c2c1 | Oc1ccccc1 | null | O=C([O-])[O-] | [Cs+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC#N | null | null | null | null | null | null | null | null | null | null | 25 | 65 | Example 5, Alternative Preparation, Step 1: A sample of 4-chloro-6-(trifluoromethyl)quinazoline (3.25 g, 13.97 mmol) was dissolved in acetonitrile (60 mL) under N2 atmosphere. The resultant cloudy solution was charged with Cs2CO3 (6.83 g, 20.96 mmol) and phenol (1.578 g, 16.77 mmol) and stirred at room temperature. After ˜65 hours, the reaction was filtered to remove the solids. The organic phase was concentrated in vacuo to yield an orange solid. The material was purified by automated flash chromatography (80 g silica gel) using 1:3 EtOAc/Hexanes as the eluant to afford the desired 4-phenoxy-6-(trifluoromethyl)quinazoline as a crystalline solid. LC/MS found (M+H)+=291.1. | FC(F)(F)c1ccc2ncnc(Oc3ccccc3)c2c1 | null | null | null |
240,509 | ord_dataset-685186618e9f4e7aaa72ac40c16ef354 | null | 1992-01-01T00:01:00 | true | [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][CH2:8][CH2:9][NH2:10])[CH:2]=1.[CH3:11][N:12]([CH3:26])[C:13]1[CH:14]=[C:15]2[CH:23]=[CH:22][CH:21]=[C:20]3[C:16]2=[C:17]([CH:25]=1)[C:18](S)=[N:19]3>C(O)C>[CH3:11][N:12]([CH3:26])[C:13]1[CH:14]=[C:15]2[CH:23]=[CH:22][CH:21]=[C:20]3[C:16]2=[C:17]([CH:25]=1)[C:18]([NH:10][CH2:9][CH2:8][CH2:7][C:3]1[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=1)=[N:19]3 | NCCCc1cccnc1 | CN(C)c1cc2c3c(cccc3c1)N=C2S | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | null | null | null | null | null | null | null | null | null | null | null | null | The reaction of equivalent molar quantities of 3-(3-pyridinyl)propanamine, 4-dimethylaminobenz(cd)indol-2thiol, and mercuric acetate in refluxing ethanol, under the conditions of Example 55 leads to the formation of the title compound. | CN(C)c1cc2c3c(cccc3c1)N=C2NCCCc1cccnc1 | null | null | null |
285,375 | ord_dataset-d63ab258f4634f87bdebbaff0a341c28 | null | 1994-01-01T00:02:00 | true | [Cl:1][C:2]1[N+:7]([O-])=[C:6]([CH3:9])[CH:5]=[CH:4][CH:3]=1.C(=O)(O)[O-].[Na+].[C:15]([O:18]C(=O)C)(=[O:17])[CH3:16]>C(OCC)(=O)C>[C:15]([O:18][CH2:9][C:6]1[CH:5]=[CH:4][CH:3]=[C:2]([Cl:1])[N:7]=1)(=[O:17])[CH3:16] | CC(=O)OC(C)=O | Cc1cccc(Cl)[n+]1[O-] | null | O=C([O-])O | [Na+] | 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 | 25 | null | A solution of the 6-chloro-2-methylpyridine-N-oxide prepared in step 1 in 750 mL acetic anhydride was heated at reflux overnight. The reaction was cooled to ambient temperature and poured into saturated aqueous sodium bicarbonate. The mixture was diluted with ethyl acetate and filtered through celite. The layers were separated and the aqueous phase was extracted with ethyl acetate. The combined extracts were dried over magnesium sulfate and concentrated. The residue was azeotroped with benzene to remove any remaining acetic acid. 2-acetoxymethyl-6-chloropyridine was isolated by vacuum distillation (b.p. 105°-110° C./1.3 torr). | CC(=O)OCc1cccc(Cl)n1 | null | null | null |
122,059 | ord_dataset-fea3ada7aaad45a0b4e7922640986af3 | null | 1984-01-01T00:09:00 | true | [N:1]1(C(OC(C)(C)C)=O)C[CH2:63][CH2:62][C@H:2]1[C:3]([NH:5][C@@H:6]([C:17]([NH:19][C@H:20]([C:28]([NH:30][C@@H:31]([C:42]([NH:44][C@H:45]([C:50]([N:52]([CH3:61])[C@H:53]([C:58]([NH2:60])=[O:59])[CH2:54][CH2:55][CH2:56][CH3:57])=[O:51])[CH2:46][CH:47]([CH3:49])[CH3:48])=[O:43])[CH2:32][C:33]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[NH:35][CH:34]=1)=[O:29])[CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:18])[CH2:7][C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[NH:10][CH:9]=1)=[O:4].FC(F)(F)C(O)=O.[CH:79](S)(S)[CH3:80]>CSC>[NH:1]1[CH2:80][CH2:79][CH2:63][CH2:62][C@H:2]1[C:3]([NH:5][C@@H:6]([C:17]([NH:19][C@H:20]([C:28]([NH:30][C@@H:31]([C:42]([NH:44][C@H:45]([C:50]([N:52]([CH3:61])[C@H:53]([C:58]([NH2:60])=[O:59])[CH2:54][CH2:55][CH2:56][CH3:57])=[O:51])[CH2:46][CH:47]([CH3:49])[CH3:48])=[O:43])[CH2:32][C:33]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[NH:35][CH:34]=1)=[O:29])[CH2:21][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)=[O:18])[CH2:7][C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[NH:10][CH:9]=1)=[O:4] | CC(S)S | CCCC[C@@H](C(N)=O)N(C)C(=O)[C@H](CC(C)C)NC(=O)[C@@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](Cc1c[nH]c2ccccc12)NC(=O)[C@@H]1CCCN1C(=O)OC(C)(C)C | 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 | CSC | null | null | null | null | null | null | null | null | null | null | null | Condensation of BocPro-DTrp-PheOH (part B of Example 17, 0.700 g.) and HDTrp-Leu-MeNleNH2 (0.520 g.) using dicyclohexylcarbodiimide and 1-hydroxybenzotriazole gave BocPro-DTrp-Phe-DTrp-Leu-MeNleNH2 in 64% yield. De-t-butoxycarbonylation of BocPro-DTrp-Phe-DTrp-Leu-MeNleNH2 (0.750 g.) using trifluoroacetic acid in dimethyl sulfide and ethanedithiol gave HPro-DTrp-Phe-DTrp-Leu-MeNleNH2, which was isolated as the amorphous white solid phosphate (1:1) salt tetrahydrate in 30% yield. | CCCC[C@@H](C(N)=O)N(C)C(=O)[C@H](CC(C)C)NC(=O)[C@@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](Cc1c[nH]c2ccccc12)NC(=O)[C@@H]1CCCCN1 | null | null | null |
1,040,042 | ord_dataset-3af92aec23dc4810b92eb0d8c60023ee | null | 2011-01-01T00:03:00 | true | [CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:14]=[C:13]([N:15]([CH3:35])[CH2:16][CH2:17][CH2:18][O:19][C:20]3[CH:21]=[C:22]4[C:26](=[CH:27][CH:28]=3)[C@H:25]([CH2:29][C:30]([O:32]CC)=[O:31])[CH2:24][CH2:23]4)[C:12]([C:36]([F:39])([F:38])[F:37])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1)[CH3:2].[Li+].[OH-].O.[CH2:43]1COC[CH2:44]1>CO>[CH2:43]([CH:29]([C@H:25]1[C:26]2[C:22](=[CH:21][C:20]([O:19][CH2:18][CH2:17][CH2:16][N:15]([C:13]3[C:12]([C:36]([F:37])([F:38])[F:39])=[CH:11][CH:10]=[C:9]([C:6]4[CH:7]=[CH:8][C:3]([CH2:1][CH3:2])=[CH:4][CH:5]=4)[N:14]=3)[CH3:35])=[CH:28][CH:27]=2)[CH2:23][CH2:24]1)[C:30]([OH:32])=[O:31])[CH3:44] | C1CCOC1 | CCOC(=O)C[C@@H]1CCc2cc(OCCCN(C)c3nc(-c4ccc(CC)cc4)ccc3C(F)(F)F)ccc21 | null | [Li+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CO | null | null | null | null | null | null | null | null | null | null | null | Following the procedure described in Example 308 and starting with ethyl ((1S)-5-[(3-{[6-(4-ethylphenyl)-3-(trifluoromethyl)-2-pyridinyl](methyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate (Example 319, 10 mg, 0.018 mmol), LiOH (0.1 mg, 0.004 mmol) in THF (1 mL), MeOH (1 mL), and water (0.5 mL), the title compound was obtained (0.0024 g, 51%). 1H NMR (400 MHz, CD2Cl2) δ 7.98 (d, 2H), 7.85 (d, 1H), 7.35-7.25 (m, 3H), 7.01 (d, 1H), 6.72 (d, 1H), 6.65 (dd, 1H), 4.02 (t, 2H), 3.83 (t, 2H), 3.47 (qt, 1H), 3.08 (s, 3H), 2.90-2.68 (m, 5H), 2.42-2.30 (m, 2H), 2.15 (qt, 2H), 1.78-1.68 (m, 1H), 1.33 (m, 3H); LC-MS: RT=4.50 min, (M+H)+ 513.2. | CCc1ccc(-c2ccc(C(F)(F)F)c(N(C)CCCOc3ccc4c(c3)CC[C@H]4C(CC)C(=O)O)n2)cc1 | null | null | null |
417,153 | ord_dataset-1cb9d78632144c5f8acfc3e9ff388678 | null | 1998-01-01T00:11:00 | true | [C:1]([O:7][CH3:8])(=[O:6])[CH2:2][C:3]([CH3:5])=[O:4].[H-].[Na+].C([Li])CCC.[CH3:16][O:17][C:18]1[CH:25]=[CH:24][C:21](C=O)=[CH:20][CH:19]=1>CCCCCC.O1CCCC1>[OH:4][C:3]1[CH2:5][CH:8]([C:21]2[CH:24]=[CH:25][C:18]([O:17][CH3:16])=[CH:19][CH:20]=2)[O:7][C:1](=[O:6])[CH:2]=1 | COC(=O)CC(C)=O | COc1ccc(C=O)cc1 | null | [H-] | [Li]CCCC | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCCCCC | C1CCOC1 | null | null | null | null | null | null | null | null | null | 0 | 0.25 | The title compound was prepared as described in General Method 1 using 5 mL of methyl acetoacetate, 2.0 g of NaH 60% dispersion in oil, 25 mL of 2.0M n-butyl lithium in hexane, 7.0 mL of 4-methoxybenzaldehyde and 150 mL of tetrahydrofuran. After addition of the aldehyde, the reaction was stirred for 15 minutes at 0° C. then allowed to warm to room temperature overnight. The crude product was triturated from diethyl ether to afford a solid (m.p.159°-162° C. (dec.)). 1H NMR (CDCl3) δ 2.91 (dd, 2 H), 3.57 (dd, 2 H), 3.83 (s, 3 H), 5.66 (dd, 1 H), 6.93-6.97 (m, 2 H), 7.30-7.34 (m, 2 H). | COc1ccc(C2CC(O)=CC(=O)O2)cc1 | null | null | null |
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