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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523,761 | ord_dataset-293186f5c9b441cab57f03cd3a18ac26 | null | 2001-01-01T00:11:00 | true | [C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][N:12]([C:15]3[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=3)[CH2:11][CH2:10]2)=[CH:5][CH:4]=1)#[N:2].N>C(O)C.[Ni]>[NH2:2][CH2:1][C:3]1[CH:4]=[CH:5][C:6]([N:9]2[CH2:10][CH2:11][N:12]([C:15]3[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=3)[CH2:13][CH2:14]2)=[CH:7][CH:8]=1 | N#Cc1ccc(N2CCN(c3ccncc3)CC2)cc1 | null | null | [Ni] | N | 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 1-(4-cyanophenyl)-4-(4-pyridyl)piperazine (1.8 g) in ethanol saturated with ammonia gas (150 ml) was hydrogenated at 150 atmospheres and 100° C. (using Raney Nickel as catalyst) in a high pressure hydrogenation apparatus for 18 hours. The solution was filtered through diatomaceous earth and the filtrate evaporated to give a solid which was purified by flash chromatography on alumina (ICN Alumina N 32-63) using a mixture of 95:5 dichloromethane:methanol as eluant. The residue was recrystallised from tetrahydrofuran/isohexane to give 1-(4-aminomethylphenyl)-4-(4-pyridyl)piperazine (1.3 g) m.p.168-170° C.; microanalysis, found: C,71.5; H,7.6; N,20.5%; C16H20N4 requires: C,71.6; H,7.5; N,20.9%; NMR: 3.2-3.4(m,4H), 3.4-3.6(m,4H), 3.65(s,2H), 6.8-6.9(d,2H), 6.9-7.0(d,2H), 7.15-7.25(d,2H), 8.15-8.25(d,2H); MS: m/z 269 (MH)+. | NCc1ccc(N2CCN(c3ccncc3)CC2)cc1 | null | 71.1 | null |
1,211,058 | ord_dataset-dc3bb1b1ac4e4229a3fc28fb559a9777 | null | 2012-01-01T00:10:00 | true | [CH3:1][N:2]([CH3:8])[CH2:3][CH2:4][CH2:5][NH:6][CH3:7].CCN(C(C)C)C(C)C.[N:18]([C:21]([CH3:27])([CH3:26])[CH2:22][C:23](Cl)=[O:24])=[N+:19]=[N-:20].[OH-].[Na+]>ClCCCl>[N:18]([C:21]([CH3:27])([CH3:26])[CH2:22][C:23]([N:6]([CH2:5][CH2:4][CH2:3][N:2]([CH3:8])[CH3:1])[CH3:7])=[O:24])=[N+:19]=[N-:20] | CC(C)(CC(=O)Cl)N=[N+]=[N-] | CNCCCN(C)C | null | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(C(C)C)C(C)C | ClCCCl | null | null | null | null | null | null | null | null | null | 0 | 1 | To a stirred ice cold solution of N1,N1,N3-trimethylpropane-1,3-diamine (5.0 g, 1 equiv, 43.0 mmol) and DIEA (11.2 mL, 1.5 equiv, 64.5 mmol) in anhydrous DCE (200 mL) was added 3-azido-3-methylbutanoyl chloride (6.95 g, 43.0 mmol) in small portions. The reaction was stirred and left at 0° C. for 1 h. Aqueous NaOH (5N, 4 equiv, 34.5 mmol) was added to the reaction mixture. The solvent and DIEA was removed via rotovap to give an oily aqueous mixture. The contents of the flask was poured into a separatory funnel and extracted with DCM (2×100 mL). The organic layer was dried over anhydrous MgSO4, filtered, concentrated and dried under high vacuum to give a crude oil (8.71 g, 84.0%). This material was used without further purification. 1H NMR (D2O, 400 MHz): δ 1.34 (t, J=7.2, 3H), 1.43 (s, 6H), 2.11-2.15 (m, 2H), 3.09 (s, 3 H), 3.35 (s, 2H), 3.41 (dt, J=7.2, 4H). LRMS (ESI+) for C11H23N5O (241.2); Found: 241 (M+). | CN(C)CCCN(C)C(=O)CC(C)(C)N=[N+]=[N-] | null | 83.9 | null |
533,606 | ord_dataset-b1a34bc8c1204d51a772ed27396c794e | null | 2002-01-01T00:02:00 | true | [C:1]([C:5]1[CH:6]=[C:7]([C:16]([CH3:19])([CH3:18])[CH3:17])[C:8]2[O:12][C:11](=[O:13])[CH:10](O)[C:9]=2[CH:15]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:20][C:21]1[CH:22]=[CH:23][C:24]([CH3:27])=[CH:25][CH:26]=1>O>[C:1]([C:5]1[CH:6]=[C:7]([C:16]([CH3:19])([CH3:17])[CH3:18])[C:8]2[O:12][C:11](=[O:13])[CH:10]([C:26]3[CH:25]=[C:24]([CH3:27])[CH:23]=[CH:22][C:21]=3[CH3:20])[C:9]=2[CH:15]=1)([CH3:4])([CH3:3])[CH3:2] | Cc1ccc(C)cc1 | CC(C)(C)c1cc2c(c(C(C)(C)C)c1)OC(=O)C2O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | null | null | null | null | null | null | null | null | null | null | null | null | To a solution of 262.3 g (1.00 mol) of 5,7-di-tert-butyl-3-hydroxy-3H-benzofuran-2-one (compound (201), Table 2, Example 1a) in 500 ml (4.05 mol) of p-xylene are added 40 g of Fulcat 22B and the mixture is refluxed for 15 hours on a water separator. The Fulcat 22B catalyst is then removed by filtration and excess p-xylene is removed by distillation on a vacuum rotaray evaporator. Crystallisation of the residue from 400 ml of methanol yields 280.6 g (80%) of 5,7-di-tert-butyl-3-(2,5-dimethylphenyl)-3H-benzofuran-2-one, m.p. 93-97° C. (compound (101), Table 1). | Cc1ccc(C)c(C2C(=O)Oc3c2cc(C(C)(C)C)cc3C(C)(C)C)c1 | null | 80.1 | null |
857,443 | ord_dataset-faa0236be76c4501841c954527cd1b6c | null | 2008-01-01T00:12:00 | true | [C:1]([O:5][C:6]([NH:8][CH:9]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[N:19]([CH2:20][C:21]#[C:22][CH3:23])[C:18]([C:24]([O:26]CC)=[O:25])=[CH:17][N:16]=2)[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl>[OH-].[K+].O1CCCC1>[C:1]([O:5][C:6]([NH:8][CH:9]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[N:19]([CH2:20][C:21]#[C:22][CH3:23])[C:18]([C:24]([OH:26])=[O:25])=[CH:17][N:16]=2)[CH2:10]1)=[O:7])([CH3:4])([CH3:2])[CH3:3] | CC#CCn1c(C(=O)OCC)cnc1N1CCCC(NC(=O)OC(C)(C)C)C1 | null | null | Cl | [K+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | null | null | A solution of 4.40 g ethyl 2-(3-tert-butoxycarbonylamino-piperidin-1-yl)-3-(but-2-ynyl)-3H-imidazole-4-carboxylate in 28 ml 4 M potassium hydroxide solution and 20 ml of tetrahydrofuran is stirred for 14 h at 100° C. Then the solution is neutralized with 2 M hydrochloric acid and extracted with dichloromethane. The combined organic extracts are dried over sodium sulphate and evaporated to dryness. | CC#CCn1c(C(=O)O)cnc1N1CCCC(NC(=O)OC(C)(C)C)C1 | null | null | null |
429,523 | ord_dataset-8cce6f317d644b348a7978a2dce3ea01 | null | 1999-01-01T00:03:00 | true | [FH:1].C(N(C(C)C)CC)(C)C.O.[F:12][C:13]([F:23])([F:22])[CH:14]([O:19][CH2:20]Cl)[C:15]([F:18])([F:17])[F:16]>>[CH2:20]([F:1])[O:19][CH:14]([C:15]([F:18])([F:17])[F:16])[C:13]([F:23])([F:22])[F:12] | F | FC(F)(F)C(OCCl)C(F)(F)F | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CCN(C(C)C)C(C)C | null | null | null | null | null | null | null | null | null | 10 | null | In an efficient fume hood, liquid hydrogen fluoride (85.1 g, 4.25 mol) was transferred into a 1 liter Teflon® reaction vessel chilled in a dry ice/acetone cold bath. The vessel was fitted with a dry ice condenser, thermocouple, and addition funnel and a portion of chloromethyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether (80.1 g) was added. A solution of diisopropylethylamine (249.0 g, 1.93 mol) in chloromethyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether (271.0 g) was slowly added while maintaining the internal temperature in the range of -5°to 10° C. After completing the addition, the mixture was transferred to a 2 liter glass boiling flask and the Teflon® vessel was rinsed out with a solution of diisopropylethylamine (307.0 g, 2.38 mol) in chloromethyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether (180.0 g) which was also transferred to the glass flask. An additional 850 g of chloromethyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether was added to the reaction flask to bring the total to 1381.1 g (6.38 mol). This mixture was heated at reflux for 16 hours. After cooling to ambient temperature, water (700 mL) was added to the reaction mixture and, after vigorous shaking, the resultant layers were separated. The lower organic layer was further washed with 700 mL of dilute hydrochloric acid (35 mL of 12 N HCl in 665 mL of water). The organic layer (1259.7 g) was analyzed by NMR and gas chromatography and was shown to consist of 63.6% fluoromethyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether (sevoflurane) and 35.4% recovered chloromethyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether, giving a 95% yield of sevoflurane based on starting material consumed. | FCOC(C(F)(F)F)C(F)(F)F | null | 95 | null |
1,224,879 | ord_dataset-cde802cdb7434a5f82a22981ccaefc4e | null | 2012-01-01T00:11:00 | true | [CH:1]1([CH:7]([C:18]2[CH:22]=[C:21]([C:23]3[CH2:24][CH2:25][S:26][CH2:27][CH:28]=3)[S:20][C:19]=2[CH2:29][CH3:30])[O:8][C:9]2[CH:17]=[CH:16][C:12]([C:13](O)=[O:14])=[CH:11][CH:10]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:31][NH:32][CH2:33][CH2:34][C:35]([O:37]CC)=[O:36]>>[CH:1]1([CH:7]([C:18]2[CH:22]=[C:21]([C:23]3[CH2:24][CH2:25][S:26][CH2:27][CH:28]=3)[S:20][C:19]=2[CH2:29][CH3:30])[O:8][C:9]2[CH:10]=[CH:11][C:12]([C:13]([N:32]([CH3:31])[CH2:33][CH2:34][C:35]([OH:37])=[O:36])=[O:14])=[CH:16][CH:17]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1 | CCOC(=O)CCNC | CCc1sc(C2=CCSCC2)cc1C(Oc1ccc(C(=O)O)cc1)C1CCCCC1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | An operation similar to that in Example 69 (9) was performed using 4-{cyclohexyl[5-(3,6-dihydro-2H-thiopyran-4-yl)-2-ethylthiophen-3-yl]methoxy}benzoic acid (234 mg) synthesized in Example 85 (4) and ethyl 3-(methylamino)propanoate (79.8 mg) to give the title compound (89.2 mg, 33%). | CCc1sc(C2=CCSCC2)cc1C(Oc1ccc(C(=O)N(C)CCC(=O)O)cc1)C1CCCCC1 | null | 32 | null |
193,723 | ord_dataset-11b3c3b41eda49e196ec983a65d3b2c0 | null | 1989-01-01T00:07:00 | true | [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[N:23]=[C:22]([O:24][CH3:25])[C:21]([F:26])=[CH:20][C:11]=1[C:12]([CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])=[O:13].[CH3:27]OC(OC)N(C)C.C(OCC)C>C1C=CC=CC=1>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:10]2[C:11](=[CH:20][C:21]([F:26])=[C:22]([O:24][CH3:25])[N:23]=2)[C:12](=[O:13])[C:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:27]1 | COC(OC)N(C)C | CCOC(=O)CC(=O)c1cc(F)c(OC)nc1Nc1ccc(F)cc1F | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | c1ccccc1 | CCOCC | null | null | null | null | null | null | null | null | null | null | null | In 4 ml of benzene was suspended 200 mg of ethyl 2-[2-(2,4-difluorophenylamino)-5-fluoro-6-methoxynicotinoyl]acetate, and 71 mg of N,N-dimethylformamide dimethylacetal was added thereto, after which the resulting mixture was subjected to reaction under reflux for 9 hours. The solvent was removed by distillation under reduced pressure, and to the residue thus obtained was added 2 ml of diethyl ether, after which the crystals thus deposited were collected by filtration to obtain 130 mg (yield 63.3%) of ethyl 1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-7-methoxy-4-oxo-1,8-naphthyridine-3-carboxylate having a melting point of 190°-192° C. | CCOC(=O)c1cn(-c2ccc(F)cc2F)c2nc(OC)c(F)cc2c1=O | null | 63.3 | null |
189,923 | ord_dataset-be83cbc722064f3696975001242f9f1a | null | 1989-01-01T00:05:00 | true | [CH3:1][C:2]1[C:7]([N+:8]([O-])=O)=[CH:6][CH:5]=[CH:4][C:3]=1[C:11]([F:14])([F:13])[F:12].[H][H]>CO.[Pd]>[NH2:8][C:7]1[C:2]([CH3:1])=[C:3]([C:11]([F:12])([F:13])[F:14])[CH:4]=[CH:5][CH:6]=1 | Cc1c([N+](=O)[O-])cccc1C(F)(F)F | [H][H] | null | [Pd] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | 25 | null | A solution of 2-methyl-3-nitrobenzotrifluoride (41.0 g, 0.2 m) in methanol (100 ml) was stirred under an atmosphere of dry nitrogen at room temperature and palladium on charcoal catalyst (10% w/w, 1.0 g) was added. The stirred mixture was warmed to 40°-45° and then hydrogen was passed into the solution at atmospheric pressure until the reduction, as observed by thin-layer chromatography, was complete (4-5 hours). The solution was cooled to room temperature and the catalyst removed by filtration. Distillation of the solvent at atmospheric pressure followed by steam distillation of the crude product gave 3-amino-2-methylbenzotrifluoride (32.2 g, 92% yield), as a pale-brown oil which slowly crystallized. | Cc1c(N)cccc1C(F)(F)F | null | 92 | null |
311,986 | ord_dataset-04982f13ed08448d93df6794846500f3 | null | 1995-01-01T00:06:00 | true | [C:1]([OH:7])(=[O:6])[CH2:2][C:3]([OH:5])=[O:4].[N+:8]([O-])([O:10]C(=O)C)=[O:9]>C(O)(=O)C.C(OC(=O)C)(=O)C>[N+:8]([CH:2]([C:1]([OH:7])=[O:6])[C:3]([OH:5])=[O:4])([O-:10])=[O:9] | CC(=O)O[N+](=O)[O-] | O=C(O)CC(=O)O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(=O)OC(C)=O | CC(=O)O | null | null | null | null | null | null | null | null | null | null | null | Nitration of malonic acid with acetyl nitrate in acetic acid/acetic anhydride was conducted to obtain nitromalonic acid. To the nitromalonic acid is added urea to obtain a condensation reaction mixture which is refluxed to form dilituric acid in situ. Various salts are separately prepared from the dilituric acid in situ using as cation sources potassium chloride, ammonia, and guanidinium chloride. The potassium diliturate salt, ammonium diliturate, guanidinium diliturate salts are each recovered and isolated by filtration. | O=C(O)C(C(=O)O)[N+](=O)[O-] | null | null | null |
200,679 | ord_dataset-31f00a039ca0424788e5e1970d25a8fd | null | 1989-01-01T00:12:00 | true | [CH3:1][C:2]1[CH:3]=[C:4]2[C:11](=[CH:12][CH:13]=1)[C:7]([CH2:8][CH2:9][NH2:10])=[CH:6][NH:5]2.Cl[CH2:15][C:16]#[N:17]>O1CCCC1.C(Cl)Cl>[CH3:1][C:2]1[CH:3]=[C:4]2[C:11]([C:7]([CH2:8][CH2:9][NH:10][CH2:15][C:16]#[N:17])=[CH:6][NH:5]2)=[CH:12][CH:13]=1 | Cc1ccc2c(CCN)c[nH]c2c1 | N#CCCl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | ClCCl | null | null | null | null | null | null | null | null | null | null | 15 | 17 g of 6-methyltryptamine were dissolved at 40° C. under inert atmosphere in 500 ml of tetrahydrofuran, and the solution was allowed to return to ambient temperature. 14.6 ml of 1,5-diaza[5,4,0]undec-5-ene were added followed by 6.2 ml of chloroacetonitrile and stirring for 15 hours. The solvent was eliminated under reduced pressure and the residue was taken up in 250 ml of methylene chloride, washed with water, dried and concentrated to dryness. The 25 g of crude product was purified by chromatography on silica (eluent: methylene chloride-ethyl acetate 3-7) to obtain 13.2 g of the expected product melting at 92° C. | Cc1ccc2c(CCNCC#N)c[nH]c2c1 | null | null | null |
1,221,527 | ord_dataset-cde802cdb7434a5f82a22981ccaefc4e | null | 2012-01-01T00:11:00 | true | [BH4-].[Na+].[C:3]1([C@@H:9]([N:11]=[C:12]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:15]3([CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]3)[CH2:14][CH2:13]2)[CH3:10])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C([O-])(O)=O.[Na+]>CO>[C:3]1([C@@H:9]([NH:11][C@@H:12]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:15]3([CH2:16][CH2:17][N:18]([C:21]([O:23][C:24]([CH3:26])([CH3:27])[CH3:25])=[O:22])[CH2:19][CH2:20]3)[CH2:14][CH2:13]2)[CH3:10])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1 | C[C@H](N=C1CCC2(CCN(C(=O)OC(C)(C)C)CC2)c2ccccc21)c1ccccc1 | null | null | O=C([O-])O | [BH4-] | [Na+] | 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 | 0 | null | At −78° C., NaBH4 (760 mg, 20 mmol) was added to a solution of the imine (B1) (7.82 g, 20 mmol) in methanol (100 ml). The reaction mixture was allowed to warm to 0° C. over 2-3 hours then treated with saturated NaHCO3 (ca. 100 ml), concentrated under reduced pressure at <30° C. to remove the solvent. The residue was extracted with ethyl acetate. The organic phase was washed with water, dried over Na2SO4 and concentrated to give (S)-tert-butyl 4-((S)-1-phenylethylamino)-3,4-dihydro-2H-spiro[naphthalene-1,4′-piperidine]-1′-carboxylate (B2) as a solid. LC-MS: m/e=421.32 (M+H). Rt=2.20 min. | C[C@H](N[C@H]1CCC2(CCN(C(=O)OC(C)(C)C)CC2)c2ccccc21)c1ccccc1 | null | null | null |
926,450 | ord_dataset-cc0899cd744f4f7f8e7f2463560faad1 | null | 2009-01-01T00:12:00 | true | Cl[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][N:7]1[C:13](=[O:14])[CH2:12][CH2:11][N:10]([C:15](=[O:26])/[CH:16]=[CH:17]/[C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[CH:19]=2)[CH2:9][CH2:8]1.[I-:27].[Na+]>>[Cl:25][C:20]1[CH:19]=[C:18](/[CH:17]=[CH:16]/[C:15]([N:10]2[CH2:11][CH2:12][C:13](=[O:14])[N:7]([CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][I:27])[CH2:8][CH2:9]2)=[O:26])[CH:23]=[CH:22][C:21]=1[Cl:24] | O=C(/C=C/c1ccc(Cl)c(Cl)c1)N1CCC(=O)N(CCCCCCl)CC1 | [I-] | 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 | 90 | 20 | In analogy to the procedure described in example 6D, 4-(5-chloro-pentyl)-1-[(E)-3-(3,4-dichloro-phenyl)-acryloyl]-[1,4]diazepan-5-one and sodium iodide were stirred at 90° C. for 20 h to give the title compound as orange oil. MS: 509.2 (MH+, 2Cl). | O=C(/C=C/c1ccc(Cl)c(Cl)c1)N1CCC(=O)N(CCCCCI)CC1 | null | null | null |
903,815 | ord_dataset-46d216f2c4374ef5b9df90427e2a4cd4 | null | 2009-01-01T00:09:00 | true | [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:22]=[CH:21][CH:20]=[C:19]3[C:15]=2[C:16](=[O:32])[C:17](=[O:31])[N:18]3[CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:33][Li]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:22]=[CH:21][CH:20]=[C:19]3[C:15]=2[C:16]([OH:32])([CH3:33])[C:17](=[O:31])[N:18]3[CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3] | CC(C)(C)OC(=O)N1CCN(c2cccc3c2C(=O)C(=O)N3Cc2cccc(F)c2)CC1 | [Li]C | 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 | -78 | null | 4-[1-(3-Fluoro-benzyl)-2,3-dioxo-2,3-dihydro-1H-indol-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (330 mg) was dissolved in 4 mL of THF and cooled to −78° C. before adding 1.6 M methyl lithium in hexaness (800 uL). The solution was stirred and warmed to room temperature, then stirred for an hour at room temperature. The reaction was quenched by addition of water and extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography afforded 315 mg of 4-[1-(3-fluoro-benzyl)-3-hydroxy-3-methyl-2-oxo-2,3-dihydro-1H-indol-4-yl]-piperazine-1-carboxylic acid tert-butyl ester. MS: 356 (M−Boc+H)+. | CC(C)(C)OC(=O)N1CCN(c2cccc3c2C(C)(O)C(=O)N3Cc2cccc(F)c2)CC1 | null | null | null |
516,111 | ord_dataset-a495451286334c5c9bbcbd48a00c1350 | null | 2001-01-01T00:09:00 | true | [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:12][CH2:11][CH2:10][NH:9]2)=[CH:4][CH:3]=1.[Cl:13][C:14]1[CH:15]=[C:16]([S:21](Cl)(=[O:23])=[O:22])[CH:17]=[CH:18][C:19]=1[CH3:20]>>[Cl:13][C:14]1[CH:15]=[C:16]([S:21]([N:9]2[CH2:10][CH2:11][CH2:12][CH:8]2[C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)(=[O:23])=[O:22])[CH:17]=[CH:18][C:19]=1[CH3:20] | Fc1ccc(C2CCCN2)cc1 | Cc1ccc(S(=O)(=O)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 | null | null | The title compound, off-white solid, m.p. 134° C. and MS: m/e=353 (M+) was prepared in accordance with the general method of example 1e from (RS)-2-(4-fluoro-phenyl)-pyrrolidine and 3-chloro-4-methyl-benzenesulfonyl chloride. | Cc1ccc(S(=O)(=O)N2CCCC2c2ccc(F)cc2)cc1Cl | null | null | null |
392,112 | ord_dataset-4bc8addcf9cf4845817557760d62d5b5 | null | 1998-01-01T00:02:00 | true | [CH2:1]([O:3][C:4]([CH:6]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH2:7][CH2:8][C:9]1[CH:15]=[C:14]([CH2:16][NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH:13]=[CH:12][C:10]=1[NH2:11])=[O:5])[CH3:2].[Br:30][C:31]1[CH:32]=[C:33]2[CH2:45][CH2:44][C@@H:43]([CH2:46][C:47](O)=[O:48])[N:35]3[C:36](=[O:42])[C:37](=[O:41])[NH:38][C:39]([CH:40]=1)=[C:34]23>C(O)(=O)C.C(OCC)(=O)C>[Br:30][C:31]1[CH:32]=[C:33]2[CH2:45][CH2:44][C@@H:43]([CH2:46][C:47](=[O:48])[NH:11][C:10]3[CH:12]=[CH:13][C:14]([CH2:16][NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[CH:15][C:9]=3[CH2:8][CH2:7][CH:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[C:25]([O:27][CH2:28][CH3:29])=[O:26])[N:35]3[C:36](=[O:42])[C:37](=[O:41])[NH:38][C:39]([CH:40]=1)=[C:34]23 | O=C(O)C[C@@H]1CCc2cc(Br)cc3[nH]c(=O)c(=O)n1c23 | CCOC(=O)C(CCc1cc(CNC(=O)OC(C)(C)C)ccc1N)C(=O)OCC | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(=O)O | CCOC(C)=O | null | null | null | null | null | null | null | null | null | null | null | A procedure similar to that described in Example 18-6) was performed with 2-(3,3-diethoxycarbonylpropyl)-4-tert-butoxycarbonylaminomethylaniline (1.5 g, 3.67 mmol) and (S)-9-bromo-5-carboxymethyl-6,7-dihydro-1H, 5H-pyrido[1,2,3-de]quinoxaline-2,3-dione (1.37 g, 4.04 mmol) to give 1.60 g of the title compound after silica gel column chromatography with 0.3% acetic acid/ethyl acetate (60%). | CCOC(=O)C(CCc1cc(CNC(=O)OC(C)(C)C)ccc1NC(=O)C[C@@H]1CCc2cc(Br)cc3[nH]c(=O)c(=O)n1c23)C(=O)OCC | null | 59.8 | null |
611,038 | ord_dataset-73916d628db147c89020b3baac642d48 | null | 2003-01-01T00:09:00 | true | [CH2:1]([N:8]([C:33](=[O:39])[C:34]([O:36]CC)=[O:35])[CH2:9][CH:10]([CH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1)[C:11]1[CH:16]=[CH:15][C:14]([C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH:20]=[CH:19][CH:18]=2)=[CH:13][CH:12]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+].Cl>C(O)C>[CH2:1]([N:8]([C:33](=[O:39])[C:34]([OH:36])=[O:35])[CH2:9][CH:10]([CH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1)[C:11]1[CH:12]=[CH:13][C:14]([C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH:20]=[CH:19][CH:18]=2)=[CH:15][CH:16]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1 | CCOC(=O)C(=O)N(Cc1ccccc1)CC(c1ccc(-c2cccc3ccccc23)cc1)C1CCCCC1 | null | null | Cl | [Na+] | [OH-] | 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 | A solution of Example 16C (50.0 mg, 0.096 mmol) in ethanol (2 mL) at room temperature was treated with 2M NaOH (0.2 mL), stirred for 2 hours, adjusted to pH 1 with 1M HCl, and extracted with ethyl acetate. The extract was dried (Na2SO4), filtered, and concentrated to provide the desired product. MS (ESI(+)) m/z 492 (M+H)+; 1H NMR (300 MHz, DMSO-d6) δ8.04-7.83 (m, 2H), 7.67-7.00 (m, 14H), 4.54-4.33 (m, 1H), 3.93-3.62 (m, 1H), 3.00-2.70 (m, 1H), 1.83-0.67 (m, 11H). | O=C(O)C(=O)N(Cc1ccccc1)CC(c1ccc(-c2cccc3ccccc23)cc1)C1CCCCC1 | null | null | null |
1,486,632 | ord_dataset-c3c1091f873b4f40827973a6f1f9b685 | null | 2014-01-01T00:09:00 | true | Br[C:2]1[CH:3]=[C:4]([N:8]2[CH2:16][CH:15]3[CH2:17][N:11]4[CH2:12][CH:13]([CH2:18][CH:9]2[CH2:10]4)[CH2:14]3)[CH:5]=[N:6][CH:7]=1.[C:19]([NH:22][C:23]1[CH:24]=[C:25](B(O)O)[CH:26]=[CH:27][CH:28]=1)(=[O:21])[CH3:20]>>[N:11]12[CH2:17][CH:15]3[CH2:14][CH:13]([CH2:18][CH:9]([N:8]([C:4]4[CH:3]=[C:2]([C:27]5[CH:28]=[C:23]([NH:22][C:19](=[O:21])[CH3:20])[CH:24]=[CH:25][CH:26]=5)[CH:7]=[N:6][CH:5]=4)[CH2:16]3)[CH2:10]1)[CH2:12]2 | CC(=O)Nc1cccc(B(O)O)c1 | Brc1cncc(N2CC3CC4CC2CN(C4)C3)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The title compound was prepared from the product of Example 65A and 3-acetamidophenylboronic acid according to General Method B: LC-MS Method D (ESI+) m/z 363.0 (M+H)+, retention time 1.21 minutes. | CC(=O)Nc1cccc(-c2cncc(N3CC4CC5CC3CN(C5)C4)c2)c1 | null | null | null |
1,724,455 | ord_dataset-36057d699ac5449e9c37eb99abf78b03 | null | 2016-01-01T00:05:00 | true | [Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[C:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[C:13]([CH3:20])[NH:12][C:11]([C:21]2[N:25]=[CH:24][N:23]([CH3:26])[N:22]=2)=[N:10]1.C1C(=O)N([Br:34])C(=O)C1>C(Cl)(Cl)Cl>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[C:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[C:13]([CH2:20][Br:34])[NH:12][C:11]([C:21]2[N:25]=[CH:24][N:23]([CH3:26])[N:22]=2)=[N:10]1 | O=C1CCC(=O)N1Br | CCOC(=O)C1=C(C)NC(c2ncn(C)n2)=NC1c1ccc(F)cc1Br | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClC(Cl)Cl | null | null | null | null | null | null | null | null | null | null | null | null | Ethyl 4-(2-bromo-4-fluorophenyl)-6-methyl-2-(1-methyl-1H-1,2,4-triazol-3-yl)-1,4-dihydropyrimidine-5-carboxylate (5 g, 12 mmol) was reacted with NBS (2.1 g, 12 mmol) in chloroform (150 mL) according to the procedure as described in Example 1, Step B to give the title compound as a yellow solid (2.4 g, 40%). The compound was characterized by the following spectroscopic data: | CCOC(=O)C1=C(CBr)NC(c2ncn(C)n2)=NC1c1ccc(F)cc1Br | null | 39.9 | null |
1,697,352 | ord_dataset-54347fcace774f89850681d6dec8009f | null | 2016-01-01T00:03:00 | true | [F:1][C:2]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15](=[O:22])[NH:14][N:13]=2)=[CH:7][C:3]=1[C:4](O)=[O:5].ON1C2C=CC=CC=2N=N1.[F:33][C:34]([F:47])([F:46])[C:35]1[N:39]2[CH2:40][CH2:41][NH:42][CH2:43][C:38]2=[C:37]([CH2:44][OH:45])[N:36]=1.C(N(CC)CC)C>CN(C)C=O>[F:1][C:2]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15](=[O:22])[NH:14][N:13]=2)=[CH:7][C:3]=1[C:4]([N:42]1[CH2:41][CH2:40][N:39]2[C:35]([C:34]([F:47])([F:33])[F:46])=[N:36][C:37]([CH2:44][OH:45])=[C:38]2[CH2:43]1)=[O:5] | OCc1nc(C(F)(F)F)n2c1CNCC2 | O=C(O)c1cc(Cc2n[nH]c(=O)c3ccccc23)ccc1F | null | On1nnc2ccccc21 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(CC)CC | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | 12 | 2-Fluoro-5-[(4-oxo-3H-phthalazin-1-yl)methyl]benzoic acid 1a (372 mg, 1.25 mmol) was dissolved in 5 mL of N,N-dimethylformamide, followed by addition of N-hydroxybenzotriazole (85 mg, 0.63 mmol), [3-(trifluoromethyl)-5,6,7,8-tetrahydro imidazo[1,5-a]pyrazin-1-yl]methanol 6a (277 mg, 1.25 mmol), 1-ethyl-(3-dimethyl-aminopropyl) carbodiimide hydrochloride (359 mg, 1.88 mmol) and triethylamine (0.3 mL, 2.5 mmol). After stirring for 12 hours, the reaction mixture was concentrated under reduced pressure and the resulting residue was purified by thin layer chromatography with elution system A to obtain 4-[[4-fluoro-3-[1-(hydroxymethyl)-3-(trifluoromethyl)-6,8-dihydro-5H-imidazo[1,5-a]pyrazine-7-carbonyl]phenyl]methyl]-2H-phthalazin-1-one 6 (400 mg, yield 64.0%) as a white solid. | O=C(c1cc(Cc2n[nH]c(=O)c3ccccc23)ccc1F)N1CCn2c(C(F)(F)F)nc(CO)c2C1 | null | 63.8 | null |
1,310,745 | ord_dataset-2d6edb8ffd434003bb508360153bd9bb | null | 2013-01-01T00:07:00 | true | [OH:1][CH:2]([CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:3]#[N:4].Cl.[CH3:18][OH:19]>>[OH:1][CH:2]([CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[C:3](=[NH:4])[O:19][CH3:18] | CO | N#CC(O)CCCCCCc1ccccc1 | 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 | 15 | A solution of 2-hydroxy-8-phenyloctanenitrile (5 g) in methanol (50 mL) was cooled to −78° C. and a stream of HCl (g) was introduced for 4 min. The mixture was stored at −10° C. for 15 h, then concentrated to yield methyl 2-hydroxy-8-phenyloctanimidate. (MH+=286). | COC(=N)C(O)CCCCCCc1ccccc1 | null | null | null |
1,712,217 | ord_dataset-3f2a531ffbae4b9eb1048afcd7953beb | null | 2016-01-01T00:04:00 | true | [N:1]([C:4]1[C:9]([F:10])=[CH:8][N:7]=[CH:6][C:5]=1[CH:11]=O)=[N+:2]=[N-:3].[Br:13][C:14]1[CH:19]=[C:18]([Cl:20])[C:17]([NH2:21])=[C:16]([Cl:22])[CH:15]=1.C(N(CC)CC)C>C(Cl)Cl.[Ti](Cl)(Cl)(Cl)Cl>[N:1]([C:4]1[C:9]([F:10])=[CH:8][N:7]=[CH:6][C:5]=1/[CH:11]=[N:21]/[C:17]1[C:18]([Cl:20])=[CH:19][C:14]([Br:13])=[CH:15][C:16]=1[Cl:22])=[N+:2]=[N-:3] | Nc1c(Cl)cc(Br)cc1Cl | [N-]=[N+]=Nc1c(F)cncc1C=O | 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 | 0 | 8 | A solution of 4-azido-5-fluoropyridine-3-carbaldehyde (10.0 g, 60.0 mmol) and 4-bromo-2,6-dichlorophenylamine (14.4 g, 60.0 mmol) in DCM (200 mL) was cooled to 0° C., under an atmosphere of nitrogen. Triethylamine (25 mL, 180 mmol) was added, followed by dropwise addition of titanium (IV) chloride solution (1 N in DCM, 36 mL, 36 mmol). The reaction mixture was stirred at 0° C. then allowed to reach room temperature overnight. The resultant mixture was concentrated under reduced pressure and the residue was suspended in toluene and filtered through a pad of Celite®. The filtrate was concentrated under reduced pressure to afford the title compound (quantitative yield). This was used in the next step without further purification. | [N-]=[N+]=Nc1c(F)cncc1/C=N/c1c(Cl)cc(Br)cc1Cl | null | null | null |
1,241,440 | ord_dataset-c544c0c663f54dbea4ddb52ddde7934e | null | 2013-01-01T00:01:00 | true | C([O:8][C:9]1[CH:10]=[C:11]([N:15]2[CH:19]=[N:18][CH:17]=[N:16]2)[CH:12]=[CH:13][CH:14]=1)C1C=CC=CC=1>CO.[Pd]>[N:15]1([C:11]2[CH:10]=[C:9]([OH:8])[CH:14]=[CH:13][CH:12]=2)[CH:19]=[N:18][CH:17]=[N:16]1 | c1ccc(COc2cccc(-n3cncn3)c2)cc1 | null | null | [Pd] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | 25 | null | 1-[3-(benzyloxy)phenyl]-1H-1,2,4-triazole (250 mg, 0.995 mmol) was dissolved in 5 mL methanol. The solution was degassed and backfilled with nitrogen. Palladium on carbon (10% w/w, 106 mg, 0.1 mmol) was then added. The reaction vessel was degassed and backfilled with hydrogen 3 times and stirred under a hydrogen balloon at room temperature. The reaction was stirred overnight. It was then diluted with 5 mL acetone and filtered through a plug of silica gel (5 g), which was washed thoroughly with acetone. Concentration afforded the product as white solid. LRMS calc: 161.1; obs: 162.2 (M+1). | Oc1cccc(-n2cncn2)c1 | null | null | null |
97,214 | ord_dataset-0bf72e95d80743729fdbb8b57a4bc0c6 | null | 1982-01-01T00:08:00 | true | [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]2[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([OH:19])[CH:17]=3)[NH:12][C:11]=2[CH3:20])=[CH:4][CH:3]=1.[CH2:21]([O:23][C:24](=[O:29])[C:25](Br)([CH3:27])[CH3:26])[CH3:22]>>[CH2:21]([O:23][C:24](=[O:29])[C:25]([O:19][C:16]1[CH:17]=[C:18]2[C:13](=[CH:14][CH:15]=1)[NH:12][C:11]([CH3:20])=[C:10]2[CH2:9][CH2:8][C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=1)([CH3:27])[CH3:26])[CH3:22] | Cc1[nH]c2ccc(O)cc2c1CCc1ccc(Cl)cc1 | CCOC(=O)C(C)(C)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 above compound was prepared from 3-[2-(4-chloro-phenyl)-ethyl]-2-methyl-1H-indole-5-ol and 2-bromo-2-methyl-propanoic acid ethylester using a procedure analogous to that of Example 10. | CCOC(=O)C(C)(C)Oc1ccc2[nH]c(C)c(CCc3ccc(Cl)cc3)c2c1 | null | null | null |
731,908 | ord_dataset-eb4226b4f7644a01a737e7547b70014a | null | 2006-01-01T00:09:00 | true | [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[N:8]=[CH:9][N:10](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH:11]=1.Cl>O1CCCC1>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[N:8]=[CH:9][NH:10][CH:11]=1 | c1ccc(C(c2ccccc2)(c2ccccc2)n2cnc(-c3ccccn3)c2)cc1 | null | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | null | null | A solution of the crude 4-(2-pyridyl)-1-trityl-1H-imidazole (0.69 g) in tetrahydrofuran (14 mL) was treated with 2 N hydrochloric acid (7.2 mL) and heated at reflux for 45 minutes. After cooling the reaction mixture was concentrated in vacuo and the residue was dissolved in dichloromethane (20 mL). The organic solution was successively washed with aqueous 1N sodium hydroxide (10 mL), water (20 mL) and brine (20 mL). The organic solution was then dried over anhydrous sodium sulfate, filtered, and concentrated in-vacuo to afford 0.12 g of crude 4-(2-pyridyl)imidazole, as a sticky white solid. | c1ccc(-c2c[nH]cn2)nc1 | null | 46.4 | null |
1,119,264 | ord_dataset-4226e9b4f9f845db967ed997270dcafc | null | 2011-01-01T00:12:00 | true | C([O:8][C:9]1[CH:14]=[C:13]([C:15]#[C:16][CH2:17][CH:18]2[CH2:22][CH2:21][CH2:20][S:19]2(=[O:24])=[O:23])[CH:12]=[CH:11][C:10]=1[N:25]1[S:29](=[O:31])(=[O:30])[NH:28][C:27](=[O:32])[CH2:26]1)C1C=CC=CC=1.B(Br)(Br)Br>C(Cl)Cl>[O:24]=[S:19]1(=[O:23])[CH2:20][CH2:21][CH2:22][CH:18]1[CH2:17][C:16]#[C:15][C:13]1[CH:12]=[CH:11][C:10]([N:25]2[S:29](=[O:31])(=[O:30])[NH:28][C:27](=[O:32])[CH2:26]2)=[C:9]([OH:8])[CH:14]=1 | O=C1CN(c2ccc(C#CCC3CCCS3(=O)=O)cc2OCc2ccccc2)S(=O)(=O)N1 | null | null | BrB(Br)Br | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | 25 | 18 | To a solution of 5-{2-benzyloxy-4-[3-(1,1-dioxotetrahydrothiophen-2-yl)-prop-1-ynyl]-phenyl}-1,1-dioxo-1,2,5-thiadiazolidin-3-one in methylene chloride (5 mL) is added BBr3 (0.35 mL of 1.0 M in methylene chloride) and the mixture is stirred at RT for 18 h. The solvent is removed under reduced pressure and the residue purified by preparative HPLC followed by lyophilization to give the title compound: (M−1)−=383; HPLC retention time=0.72 min. (Method A) | O=C1CN(c2ccc(C#CCC3CCCS3(=O)=O)cc2O)S(=O)(=O)N1 | null | null | null |
1,354,074 | ord_dataset-6034127657614f02860ed057b62b882e | null | 2013-01-01T00:10:00 | true | [F:1][C:2]1[CH:7]=[CH:6][C:5]([C@:8]2([CH2:32][CH2:33][CH2:34][OH:35])[O:13][C:12](=[O:14])[N:11]([C@H:15]([C:17]3[CH:22]=[CH:21][C:20](B4OC(C)(C)C(C)(C)O4)=[CH:19][CH:18]=3)[CH3:16])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.Cl[C:37]1[CH:42]=[CH:41][N:40]=[CH:39][N:38]=1>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@:8]2([CH2:32][CH2:33][CH2:34][OH:35])[O:13][C:12](=[O:14])[N:11]([C@H:15]([C:17]3[CH:18]=[CH:19][C:20]([C:37]4[CH:42]=[CH:41][N:40]=[CH:39][N:38]=4)=[CH:21][CH:22]=3)[CH3:16])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1 | C[C@@H](c1ccc(B2OC(C)(C)C(C)(C)O2)cc1)N1CC[C@](CCCO)(c2ccc(F)cc2)OC1=O | Clc1ccncn1 | null | null | null | null | null | null | null | 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 (R)-6-(4-fluorophenyl)-6-(3-hydroxypropyl)-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-oxazinan-2-one and 4-chloropyrimidine following a procedure analogous to that described in Example 1 Step 2. LC-MS Method 2 tR=1.172, m/z=392.1; 1H NMR (CDCl3) 1.28-1.40 (m, 1H), 1.52 (m, 3H), 1.64 (m, 2H), 1.81-1.99 (m, 2H), 2.09-2.37 (m, 3H), 2.90 (m, 1H), 3.51 (t, 2H), 5.68 (m, 1H), 6.88-7.07 (m, 3H), 7.16-7.28 (m, 3H), 7.58 (m, 1H), 7.79 (d, 2H), 8.61-8.80 (d, 1H), 9.18 (s, 1H). | C[C@@H](c1ccc(-c2ccncn2)cc1)N1CC[C@](CCCO)(c2ccc(F)cc2)OC1=O | null | null | null |
707,525 | ord_dataset-c8069773c1a148aca8ab417108daacc5 | null | 2006-01-01T00:05:00 | true | [C:1]([C:3]1[CH:4]=[C:5]([NH:9][C:10](=S)[C:11]2[CH:16]=[C:15]([N+:17]([O-:19])=[O:18])[CH:14]=[CH:13][C:12]=2F)[CH:6]=[CH:7][CH:8]=1)#[N:2].O.[NH2:23][NH2:24]>C(O)CCC>[N+:17]([C:15]1[CH:16]=[C:11]2[C:12](=[CH:13][CH:14]=1)[NH:24][N:23]=[C:10]2[NH:9][C:5]1[CH:4]=[C:3]([CH:8]=[CH:7][CH:6]=1)[C:1]#[N:2])([O-:19])=[O:18] | NN | N#Cc1cccc(NC(=S)c2cc([N+](=O)[O-])ccc2F)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CCCCO | null | null | null | null | null | null | null | null | null | null | null | To a solution of N-(3-Cyano-phenyl)-2-fluoro-5-nitro-thiobenzamide (8.56 g; 0.028 mol) in n-butanol (300 mL) was added hydrazine hydrate (2.54 mL; 0.053 mol) and the solution refluxed for 3 hours. The reaction mixture was concentrated in vacuo and triturated with hot ethanol to afford the title compound as a red solid (4.93 g; 62%). 1H NMR (400 MHz, DMSO-d6) δH 7.30 (1H, d), 7.45–7.60 (2H, m), 7.90 (1H, d), 8.20 (1H, d), 8.25 (1H, s), 9.20 (1H, s), 9.85 (1H, s). Mass Spectrum (ES−) m/e=278.28. | N#Cc1cccc(Nc2n[nH]c3ccc([N+](=O)[O-])cc23)c1 | null | 63.1 | null |
433,040 | ord_dataset-386da077ab2340638cada986e2ef0770 | null | 1999-01-01T00:07:00 | true | CS([O:5][CH:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH2:8][CH2:7]1)(=O)=O.O[C:18]1[CH:25]=[CH:24][C:21]([CH:22]=[O:23])=[CH:20][CH:19]=1.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[CH2:15]([O:14][C:12]([N:9]1[CH2:10][CH2:11][CH:6]([O:5][C:18]2[CH:25]=[CH:24][C:21]([CH:22]=[O:23])=[CH:20][CH:19]=2)[CH2:7][CH2:8]1)=[O:13])[CH3:16] | CCOC(=O)N1CCC(OS(C)(=O)=O)CC1 | O=Cc1ccc(O)cc1 | 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 | 80 | 12 | To a mixture of 1-(ethoxycarbonyl)piperidin-4-yl methanesulfonate (10 g) and 4-hydroxy benzaldehyde (5.8 g) in dry DMF (75 ml), K2CO3 (11 g) was added and the mixture was stirred at 80° C. for 12 h. At the end of this time, the reaction mixture was cooled, added water and extracted with EtOAc. The EtOAc extract was washed with 5% aqueous Na2CO3 solution followed by brine and dried over anhydrous sodium sulphate. The solvent was then removed by distillation under reduced pressure to give 7 g (63.6%) of the title compound as a semi solid. | CCOC(=O)N1CCC(Oc2ccc(C=O)cc2)CC1 | null | 63.4 | null |
669,991 | ord_dataset-e90cd41afe844e49875435eb99903799 | null | 2005-01-01T00:05:00 | true | CC1(C)[O:6][C:5](=[CH:7][C:8]([N:10]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[O:11][CH3:12])=[O:9])[C:4](=[O:21])O1.[CH3:23][C:24]1[C:28]([S:29]([NH2:32])(=[O:31])=[O:30])=[C:27]([CH3:33])[O:26][N:25]=1>>[F:20][C:17]1[CH:16]=[CH:15][C:14]([CH2:13][N:10]([O:11][CH3:12])[C:8](=[O:9])[CH:7]=[C:5]([OH:6])[C:4]([NH:32][S:29]([C:28]2[C:24]([CH3:23])=[N:25][O:26][C:27]=2[CH3:33])(=[O:30])=[O:31])=[O:21])=[CH:19][CH:18]=1 | CON(Cc1ccc(F)cc1)C(=O)C=C1OC(C)(C)OC1=O | Cc1noc(C)c1S(N)(=O)=O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | 2-(2,2-Dimethyl-5-oxo-[1,3]dioxolan-4-ylidene)-N-(4-fluoro-benzyl)-N-methoxy-acetamide was treated with 3,5-dimethyl-isoxazole-4-sulfonic acid amide as described in the preparation of compound 1 to yield the title compound. LCMS (M+H) calcd for C17H19FN3O7S: 428.1; found: 428.0. 1H NMR (500 MHz, CDCl3) δ: 2.44 (s, 3), 2.75 (s, 3), 3.65 (s, 3), 4.77 (s, 2), 6.45 (s, 1), 7.01 (m, 2), 7.26 (m, 2). 13C NMR (125 MHz, CDCl3) δ:10.83, 13.24, 48.33, 63.23, 92.57, 114.23, 115.71, 115.89, 130.19, 130.29, 130.96, 157.85, 158.89, 159.44, 161.71, 163.68, 170.81, 177.09. | CON(Cc1ccc(F)cc1)C(=O)C=C(O)C(=O)NS(=O)(=O)c1c(C)noc1C | null | null | null |
1,282,275 | ord_dataset-d5c54236ecd94d61aaa071461bcfc426 | null | 2013-01-01T00:04:00 | true | C(OC([N:8]1[CH2:12][CH:11]([O:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[C:16]([F:21])[CH:15]=2)[CH:10]2[N:22]([C:25](=[O:48])[CH:26]([NH:31][C:32](=[O:47])[CH:33]([N:35]([C:37]([O:39][CH2:40][C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)=[O:38])[CH3:36])[CH3:34])[C:27]([CH3:30])([CH3:29])[CH3:28])[CH2:23][CH2:24][CH:9]12)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH2:40]([O:39][C:37](=[O:38])[N:35]([CH:33]([C:32](=[O:47])[NH:31][CH:26]([C:25]([N:22]1[CH2:23][CH2:24][CH:9]2[NH:8][CH2:12][CH:11]([O:13][C:14]3[CH:19]=[CH:18][C:17]([F:20])=[C:16]([F:21])[CH:15]=3)[CH:10]12)=[O:48])[C:27]([CH3:28])([CH3:30])[CH3:29])[CH3:34])[CH3:36])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1 | CC(C(=O)NC(C(=O)N1CCC2C1C(Oc1ccc(F)c(F)c1)CN2C(=O)OC(C)(C)C)C(C)(C)C)N(C)C(=O)OCc1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | O=C(O)C(F)(F)F | null | null | null | null | null | null | null | null | null | 0 | 2 | The Boc-containing compound 34 (2.0 g, 3.0 mmol) was dissolved in DCM (30 mL) and cooled to 0° C. TFA (10 mL) was added and the reaction mixture was slowly warmed to ambient temperature. After 2 h, the reaction mixture was concentrated in vacuo and the crude residue was dissolved in EtOAc and washed successively with saturated aqueous NaHCO3 and brine. The organic extract was dried over anhydrous Na2SO4, filtered, and concentrated to afford 1.75 g of compound 35 as a white solid. Mass spectrum, m/z [573.1] (M+H)+. | CC(C(=O)NC(C(=O)N1CCC2NCC(Oc3ccc(F)c(F)c3)C21)C(C)(C)C)N(C)C(=O)OCc1ccccc1 | null | 101.9 | null |
377,235 | ord_dataset-846d411edee44814931e062174d7ef12 | null | 1997-01-01T00:09:00 | true | C([NH:8][CH2:9][C:10]1[O:14][N:13]=[C:12]([C:15]2[N:16]=[CH:17][N:18]3[C:24]4[CH:25]=[CH:26][CH:27]=[C:28]([C:29]([F:32])([F:31])[F:30])[C:23]=4[C:22](=[O:33])[N:21]4[CH2:34][CH2:35][C@H:20]4[C:19]=23)[N:11]=1)(OC(C)(C)C)=O>FC(F)(F)C(O)=O>[NH2:8][CH2:9][C:10]1[O:14][N:13]=[C:12]([C:15]2[N:16]=[CH:17][N:18]3[C:24]4[CH:25]=[CH:26][CH:27]=[C:28]([C:29]([F:32])([F:31])[F:30])[C:23]=4[C:22](=[O:33])[N:21]4[CH2:34][CH2:35][C@H:20]4[C:19]=23)[N:11]=1 | CC(C)(C)OC(=O)NCc1nc(-c2ncn3c2[C@@H]2CCN2C(=O)c2c-3cccc2C(F)(F)F)no1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O=C(O)C(F)(F)F | null | null | null | null | null | null | null | null | null | null | null | null | 7.8 g (15.9 mmol) of crude (S)-1-[5-(N-BOC-aminomethyl)-1,2,4-oxadiazol-3-yl]-8-trifluoromethyl-12,12a-dihydro-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-one and 30 ml of trifluoroacetic acid were stirred at room temperature for 1hour. The solution was evaporated. The residue was dissolved in water and washed three times with methylene chloride. The aqueous phase was made alkaline with conc. ammonia and extracted nine times with ethyl acetate (a total of about 1 I). By evaporating the organic phases, combined and dried over magnesium sulfate, there were obtained 4.57 g (73%) of (S)-1-(5-aminomethyl-1,2,4-oxadiazol-3-yl)-8-trifluoromethyl-12,12a-dihydro-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-one, which was used without further purification as the starting material for the Example described hereinafter. | NCc1nc(-c2ncn3c2[C@@H]2CCN2C(=O)c2c-3cccc2C(F)(F)F)no1 | null | 73.6 | null |
170,242 | ord_dataset-37d3220f708c49ad839bab296b722248 | null | 1988-01-01T00:03:00 | true | [Cl:1][C:2]1[CH:3]=[C:4]([CH:18]=[CH:19][C:20]=1[Cl:21])[CH2:5][N:6]1[C:15](=[O:16])[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[NH:8][C:7]1=[O:17].[H-].[Na+].Br[CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27].Cl>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:18]=[CH:19][C:20]=1[Cl:21])[CH2:5][N:6]1[C:15](=[O:16])[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[N:8]([CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27])[C:7]1=[O:17] | O=c1[nH]c2ccccc2c(=O)n1Cc1ccc(Cl)c(Cl)c1 | CCOC(=O)CBr | 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 | 0 | null | To a suspension of 3-(3,4-dichlorobenzyl)-1,2,3,4-tetrahydro-2,4-dioxoquinazoline (1 g) in N,N-dimethylformamide (15 ml) was added sodium hydride (60% in mineral oil, 0.17 g) with stirring at 0° C. and the mixture was stirred for 15 minutes at the same temperature. To this mixture was added ethyl bromoacetate (0.45 ml) and the mixture was stirred for 1 hour at room temperature. The reaction mixture was poured into diluted hydrochloric acid and extracted with ethyl acetate. The extract was washed with brine, dried and evaporated to give a residue. Thus obtained product was purified by recrystallization from isopropyl ether to give ethyl 2-[3-(3,4-dichlorobenzyl)-1,2,3,4-tetrahydro-2,4-dioxoquinazolin-1-yl]acetate (1.21 g). | CCOC(=O)Cn1c(=O)n(Cc2ccc(Cl)c(Cl)c2)c(=O)c2ccccc21 | null | null | null |
195,381 | ord_dataset-b83b16f2fb1a4f8782f3d82c1766cc6b | null | 1989-01-01T00:08:00 | true | [F:1][C:2]1[CH:13]=[CH:12][C:5]([O:6][CH2:7][C@H:8]([OH:11])[CH2:9][OH:10])=[CH:4][CH:3]=1.N1C=CC=CC=1.CC1C=CC(S(Cl)(=O)=O)=CC=1>ClC(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][CH2:7][C@@H:8]([OH:11])[CH2:9][OH:10])=[CH:12][CH:13]=1 | OC[C@@H](O)COc1ccc(F)cc1 | null | null | Cc1ccc(S(=O)(=O)Cl)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | c1ccncc1 | ClC(Cl)Cl | null | null | null | null | null | null | null | null | null | 25 | 8 | To a stirred mixture of 11 parts of (-)-(R)-3-(4-fluorophenoxy)-1,2-propanediol, 23.3 parts of pyridine and 240 parts of trichloromethane were added 12.3 parts of 4-methylbenzenesulfonyl chloride. The whole was stirred overnight at room temperature. It was washed successively with acid water, a sodium carbonate solution and water, dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (98:2 by volume) as eluent. The pure fractions were collected and the eluent was evaporated, yielding 13.5 parts (67.2%) of (+)-(S)-3-(4-fluorophenoxy)-1,2-propanediol, O1 -4-methylbenzenesulfonate; [α]D =+11.11° (c=0.5% in trichloromethane) (147). | OC[C@H](O)COc1ccc(F)cc1 | null | 67.2 | null |
829,329 | ord_dataset-47bd90bf5ec74fcd99ce250a56e18c8f | null | 2008-01-01T00:07:00 | true | [C:1]([C:3]1[N:8]=[C:7]([CH2:9][NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH:6]=[CH:5][CH:4]=1)#[N:2].[C:18](OC)(=[O:26])[C:19]1[C:20](=[CH:22][CH:23]=[CH:24][CH:25]=1)[SH:21].C(N(CC)CC)C>C1(C)C=CC=CC=1>[O:26]=[C:18]1[C:19]2[CH:25]=[CH:24][CH:23]=[CH:22][C:20]=2[S:21][C:1]([C:3]2[N:8]=[C:7]([CH2:9][NH:10][C:11](=[O:17])[O:12][C:13]([CH3:14])([CH3:16])[CH3:15])[CH:6]=[CH:5][CH:4]=2)=[N:2]1 | COC(=O)c1ccccc1S | CC(C)(C)OC(=O)NCc1cccc(C#N)n1 | 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 | null | null | tert-Butyl (6-cyano-2-pyridyl)methylcarbamate (1.6 g, 6.8 mmol) and methyl thiosalicylate (1.8 g, 10.9 mmol) were dissolved in toluene (6 ml), and triethylamine (3.0 ml, 21.5 mmol) was added thereto. The mixture was refluxed for 20 hrs. After cooling, the precipitates were collected by filtration and dissolved in chloroform. The solution was subjected to a silica gel column chromatography. The fractions eluted with chloroform-methanol (20:1, v/v) were collected, concentrated and recrystallized from hexane-chloroform to give the titled compound (1.8 g, 72%) as pale yellow crystals. | CC(C)(C)OC(=O)NCc1cccc(-c2nc(=O)c3ccccc3s2)n1 | null | 71.7 | null |
1,079,131 | ord_dataset-afd812677c134591a99f46ce28de2524 | null | 2011-01-01T00:08:00 | true | [CH2:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][C:7]([N+:13]([O-:15])=[O:14])=[C:6]2O)[CH3:2].O=P(Cl)(Cl)[Cl:19]>>[Cl:19][C:6]1[C:5]2[C:10](=[CH:11][CH:12]=[C:3]([CH2:1][CH3:2])[CH:4]=2)[N:9]=[CH:8][C:7]=1[N+:13]([O-:15])=[O:14] | O=P(Cl)(Cl)Cl | CCc1ccc2ncc([N+](=O)[O-])c(O)c2c1 | null | null | null | null | null | null | null | 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 is prepared in analogy to Example 19c starting from 3.6 g (16.49 mmol) 6-ethyl-3-nitro-quinolin-4-ol (Example 49d) and 24 ml POCl3. mp: 290-295° C.; MS: 237 (M++1); HPLC: tret=13.72 min (Grad 1). | CCc1ccc2ncc([N+](=O)[O-])c(Cl)c2c1 | null | null | null |
1,466,640 | ord_dataset-fd1fa959d6264608b0b7fcda16741bfd | null | 2014-01-01T00:08:00 | true | [N+:1]([C:4]1[CH:12]=[C:11]2[C:7]([CH:8]=[CH:9][NH:10]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].[C:13]([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[CH3:13][N:10]1[C:11]2[C:7](=[CH:6][CH:5]=[C:4]([N+:1]([O-:3])=[O:2])[CH:12]=2)[CH:8]=[CH:9]1 | O=C([O-])[O-] | O=[N+]([O-])c1ccc2cc[nH]c2c1 | null | [K+] | null | 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 | 8 | To a solution of 6-nitroindole (4.05 g 25 mmol) in DMF (50 mL) was added K2CO3 (8.63 g, 62.5 mmol) and Me (5.33 g, 37.5 mmol). After stirring at room temperature overnight, the mixture was poured into water and extracted with ethyl acetate. The combined organic layers were dried over Na2SO4 and concentrated under vacuum to give the product 1-methyl-6-nitro-1H-indole (4.3 g, 98%). | Cn1ccc2ccc([N+](=O)[O-])cc21 | null | 97.6 | null |
1,205,469 | ord_dataset-fb72428f30234761b4216139dc228d0c | null | 2012-01-01T00:09:00 | true | N1C=CN=C1.[CH3:6][C:7]([Si:10](Cl)([CH3:12])[CH3:11])([CH3:9])[CH3:8].[Cl:14][C:15]1[C:16]([CH3:41])=[C:17]([NH:23][C@H:24]([CH2:39][OH:40])[C:25]([NH:27][NH:28][C:29](=[O:38])[C:30]2[CH:35]=[CH:34][C:33]([C:36]#[N:37])=[CH:32][CH:31]=2)=[O:26])[CH:18]=[CH:19][C:20]=1[C:21]#[N:22].O>CN(C=O)C>[Si:10]([O:40][CH2:39][C@@H:24]([NH:23][C:17]1[CH:18]=[CH:19][C:20]([C:21]#[N:22])=[C:15]([Cl:14])[C:16]=1[CH3:41])[C:25]([NH:27][NH:28][C:29](=[O:38])[C:30]1[CH:35]=[CH:34][C:33]([C:36]#[N:37])=[CH:32][CH:31]=1)=[O:26])([C:7]([CH3:9])([CH3:8])[CH3:6])([CH3:12])[CH3:11] | Cc1c(N[C@H](CO)C(=O)NNC(=O)c2ccc(C#N)cc2)ccc(C#N)c1Cl | CC(C)(C)[Si](C)(C)Cl | null | c1c[nH]cn1 | null | 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 | 20 | Imidazole (1.3 g, 19.1 mol) and TBDMS-Cl (1.73 g, 11.46 mmol) were added sequentially to a pre-cooled (0° C.) solution of (R)—N′-(2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxypropanoyl)-4-cyanobenzohydrazide (1.52 g, 3.82 mmol) in DMF (145 mL). The reaction mixture was allowed to warm to room temperature and stirred for 20 h, whereupon the solution was poured into H2O (200 mL). The white precipitate was filtered, washed with H2O (35 mL) and taken up in CH2Cl2 (300 mL). This organic layer was washed with brine (1×160 mL), dried (Na2SO4), filtered and concentrated to provide the title compound (1.52 g, 78%). 1H NMR (400 MHz, acetone-d6, δ in ppm) 9.6 (br s, 1H), 7.97 (d, J=8.0 Hz, 2H), 7.80 (d, J=9 Hz, 2H), 7.41 (d, J=8 Hz, 1H), 6.63 (d, J=8 Hz, 3H), 5.45 (d, J=8 Hz, 1H), 4.29-4.23 (m, 1H), 4.05-4.02 (m, 2H), 2.21 (s, 3H), 0.79 (s, 9H), 0.01 (s, 6H). | Cc1c(N[C@H](CO[Si](C)(C)C(C)(C)C)C(=O)NNC(=O)c2ccc(C#N)cc2)ccc(C#N)c1Cl | null | 77.7 | null |
103,328 | ord_dataset-bdb961f26fac426eaa2de8f54a284acf | null | 1983-01-01T00:02:00 | true | [N+]([C:4]1[CH:13]=[CH:12][CH:11]=[C:6]([C:7]([O:9]C)=[O:8])[C:5]=1[C:14]([O:16][CH3:17])=[O:15])([O-])=O.[CH3:18][O-:19].[Na+]>CN(C)P(=O)(N(C)C)N(C)C.O>[C:14]([C:5]1[C:4]([O:19][CH3:18])=[CH:13][CH:12]=[CH:11][C:6]=1[C:7]([OH:9])=[O:8])([O:16][CH3:17])=[O:15] | C[O-] | COC(=O)c1cccc([N+](=O)[O-])c1C(=O)OC | null | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)P(=O)(N(C)C)N(C)C | O | null | null | null | null | null | null | null | null | null | null | 44 | Dimethyl 3-nitrophthalate (4.8 g, 20 mmol) was added to a cold solution of sodium methoxide (2.61 g, 48.3 mmol) in dry hexamethylphosphoric triamide (75 ml). The resulting dark solution was gradually brought to room temperature and the reaction mixture was stirred for 44 hrs. It was then diluted with water (125 ml) and extracted with benzene. (This extract contained a variable quantity of dimethyl 3-methoxyphthalate. The aqueous layer was acidified with hydrochloric acid and extracted with benzene. The combined organic layers were washed with water (5×30 ml) and then brine (1×15 ml), dried over sodium sulfate, filtered and evaporated to give 3.25 g (75%) of 2-carbomethoxy-3-methoxybenzoic acid, mp 140°-141° C. (benzene). Identity was confirmed by mixture mp, co-chromatography and spectroscopic comparison with an authentic sample. 1H NMR (CDCl3) δ 3.86 (3H, s, ArCO2CH3), 3.93 (3H, s, ArOCH3), 7.13 (1H, dd, J=8,2 Hz, ArH4), 7.43 (1H, t, J=8 Hz, ArH5), 7.68 (1H, dd, J=8,2 Hz, ArH6, 10.50 (1H, broad s, ArCO2H); IR (KBr) 3200 (br), 2960, 1740, 1690, 1585, 1475, 1310, 1050 cm-1 , etc.; mass spectrum m/e (rel. intensity) 211 (m+ +1,5%), 210 M+, 30%), 193 (M+ -OH, 2%), 180 (M+ -2CH3, 100%), 179 (M+ -OCH3, 10%), etc. | COC(=O)c1c(OC)cccc1C(=O)O | null | 77.3 | null |
729,787 | ord_dataset-eb4226b4f7644a01a737e7547b70014a | null | 2006-01-01T00:09:00 | true | [C:1]1([CH:7]([O:14][C:15]([C:17]2[N:18]3[CH:21]([CH2:22][CH2:23][C:24]=2[SH:25])[C@@H:20]([NH:26][C:27](=[O:57])/[C:28](/[C:50]2[N:51]=[C:52]([NH2:56])[S:53][C:54]=2[Cl:55])=[N:29]\[O:30][C:31]([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:19]3=[O:58])=[O:16])[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:59]([O:63][C:64]([NH:66][CH2:67][CH2:68][S:69][CH2:70][C:71]1[CH:72]=[N:73][CH:74]=[CH:75][C:76]=1Cl)=[O:65])([CH3:62])([CH3:61])[CH3:60].O>CN(C)C=O>[C:1]1([CH:7]([O:14][C:15]([C:17]2[N:18]3[CH:21]([CH2:22][CH2:23][C:24]=2[S:25][C:76]2[CH:75]=[CH:74][N:73]=[CH:72][C:71]=2[CH2:70][S:69][CH2:68][CH2:67][NH:66][C:64]([O:63][C:59]([CH3:62])([CH3:61])[CH3:60])=[O:65])[C@@H:20]([NH:26][C:27](=[O:57])/[C:28](/[C:50]2[N:51]=[C:52]([NH2:56])[S:53][C:54]=2[Cl:55])=[N:29]\[O:30][C:31]([C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=2)[C:19]3=[O:58])=[O:16])[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1 | CC(C)(C)OC(=O)NCCSCc1cnccc1Cl | Nc1nc(/C(=N/OC(c2ccccc2)(c2ccccc2)c2ccccc2)C(=O)N[C@H]2C(=O)N3C(C(=O)OC(c4ccccc4)c4ccccc4)=C(S)CCC23)c(Cl)s1 | 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 | null | 8 | To a solution of (7R)-7-[(Z)-2-(2-amino-5-chlorothiazol-4-yl)-2-(triphenylmethoxyimino]-acetamido]-3-mercapto-8-oxo-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylate diphenylmethyl ester (3.0 g, 0.0036 mol) in dimethylformamide (30 mL) was added 3-(N-tert-butoxycarbonylaminoethylthiomethyl)-4-chloropyridine (1.3 g, 0.0043 mol) at room temperature. After stirring overnight, the reaction mixture was treated with water (200 mL), and the solid that formed was filtered and dried to afford the crude title compound (2.9 g). | CC(C)(C)OC(=O)NCCSCc1cnccc1SC1=C(C(=O)OC(c2ccccc2)c2ccccc2)N2C(=O)[C@H](NC(=O)/C(=N\OC(c3ccccc3)(c3ccccc3)c3ccccc3)c3nc(N)sc3Cl)C2CC1 | null | 73.7 | null |
1,097,806 | ord_dataset-af85e6f81c2d49f08086afd6d9e6959c | null | 2011-01-01T00:10:00 | true | [N:1]1[CH:2]=[CH:3][N:4]2[C:9]=1[CH:8]=[CH:7][C:6]([O:10][C:11]1[CH:12]=[C:13]([CH:15]=[CH:16][CH:17]=1)[NH2:14])=[N:5]2.C(N(CC)CC)C.[C:25]1([N:31]=[C:32]=[O:33])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>O1CCCC1>[N:1]1[CH:2]=[CH:3][N:4]2[C:9]=1[CH:8]=[CH:7][C:6]([O:10][C:11]1[CH:12]=[C:13]([NH:14][C:32]([NH:31][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[O:33])[CH:15]=[CH:16][CH:17]=1)=[N:5]2 | O=C=Nc1ccccc1 | Nc1cccc(Oc2ccc3nccn3n2)c1 | 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 | 25 | 18 | To a solution of 3-(imidazo[1,2-b]pyridazin-6-yloxy)aniline (181 mg, 0.80 mmol) and triethylamine (0.011 mL, 0.08 mmol) in tetrahydrofuran (10 mL) was added phenyl isocyanate (0.104 mL, 0.96 mmol), and the mixture was stirred at room temperature for 18 hr. The reaction mixture was concentrated under reduced pressure, and the residue was purified by NH silica gel column chromatography (ethyl acetate/methanol=100/0→90/10) and precipitated from ethyl acetate to give the title compound (196 mg, 71%) as a white powder. | O=C(Nc1ccccc1)Nc1cccc(Oc2ccc3nccn3n2)c1 | null | 70.9 | null |
1,493,798 | ord_dataset-366bdd9ee72d474cbe6f3f9e54dd96d2 | null | 2014-01-01T00:10:00 | true | [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8](Cl)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[Cl:12][C:13]1[CH:25]=[N:24][C:16]2[NH:17][C:18]3[CH2:23][CH2:22][NH:21][CH2:20][C:19]=3[C:15]=2[CH:14]=1.O>N1C=CC=CC=1>[Cl:12][C:13]1[CH:25]=[N:24][C:16]2[NH:17][C:18]3[CH2:23][CH2:22][N:21]([S:8]([C:5]4[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=4)(=[O:10])=[O:9])[CH2:20][C:19]=3[C:15]=2[CH:14]=1 | Clc1cnc2[nH]c3c(c2c1)CNCC3 | O=S(=O)(Cl)c1ccc(Cl)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | c1ccncc1 | O | null | null | null | null | null | null | null | null | null | 25 | 8 | 4-Chlorobenzenesulfonyl chloride (56 mg, 0.26 mmol) was added to a solution of 3-chloro-6,7,8,9-tetrahydro-5H-dipyrido[2,3-b;3′,4′-d]pyrrole (50 mg, 0.24 mmol) in pyridine (2 mL), and the reaction was stirred overnight at room temperature. The reaction mixture was added to water (20 mL), and the resulting precipitate was filtered and dried under vacuum to provide 33 (92 mg, 99% yield) as a yellow solid. LC-MS (M+H=382, obsd.=382). | O=S(=O)(c1ccc(Cl)cc1)N1CCc2[nH]c3ncc(Cl)cc3c2C1 | null | 100.3 | null |
1,476,559 | ord_dataset-c3c1091f873b4f40827973a6f1f9b685 | null | 2014-01-01T00:09:00 | true | [NH2:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[SH:9].Br[CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH2:11]([S:9][C:3]1[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=1[NH2:1])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1 | Nc1cc(Cl)ccc1S | BrCc1ccccc1 | null | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | null | null | Following General Procedure A, the title compound (819 mg, 100%) was prepared from 2-amino-4-chlorobenzenethiol (700 mg, 4.39 mmol), (bromomethyl)benzene (560 mg, 2.92 mmol), K2CO3 (2.0 g, 14.62 mmol) in DMF (20 ml). | Nc1cc(Cl)ccc1SCc1ccccc1 | null | 112.3 | null |
1,264,903 | ord_dataset-d3580a12b15e46cc91aa73f4f1a4a8cc | null | 2013-01-01T00:03:00 | true | [Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[S:16][N:15]=[C:14]([C:17]3[C:18]([CH2:26][CH3:27])=[C:19]([CH2:23][CH:24]=O)[CH:20]=[CH:21][CH:22]=3)[N:13]=2)[CH:5]=[N:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].[NH:28]1[CH2:33][CH2:32][CH:31]([C:34]([O:36][CH2:37][CH3:38])=[O:35])[CH2:30][CH2:29]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[S:16][N:15]=[C:14]([C:17]3[C:18]([CH2:26][CH3:27])=[C:19]([CH2:23][CH2:24][N:28]4[CH2:33][CH2:32][CH:31]([C:34]([O:36][CH2:37][CH3:38])=[O:35])[CH2:30][CH2:29]4)[CH:20]=[CH:21][CH:22]=3)[N:13]=2)[CH:5]=[N:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10] | CCc1c(CC=O)cccc1-c1nsc(-c2cnc(OC(C)C)c(Cl)c2)n1 | CCOC(=O)C1CCNCC1 | null | CC(=O)O[BH-](OC(C)=O)OC(C)=O | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | null | 8 | To a solution of [3-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-thiadiazol-3-yl)-2-ethylphenyl]acetaldehyde (D111) (2 g, 2.488 mmol) in Dichloromethane (DCM) (10 mL) was added ethyl 4-piperidinecarboxylate (0.430 g, 2.74 mmol). The reaction solution was stirred for 5 min before sodium triacetoxyborohydride (0.791 g, 3.73 mmol) was added. The reaction solution was stirred overnight. The reaction solution was washed with water, dried, concentrated and purified by ISCO column chromatography to afford the crude product ethyl 1-{2-[3-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-thiadiazol-3-yl)-2-ethylphenyl]ethyl}-4-piperidinecarboxylate (D112) (450 mg). MS (ES): C28H35ClN4O3S requires 542.2. found 543.2 (M+H+). | CCOC(=O)C1CCN(CCc2cccc(-c3nsc(-c4cnc(OC(C)C)c(Cl)c4)n3)c2CC)CC1 | null | 33.3 | null |
620,781 | ord_dataset-c9f990dde2dc45d0948ecbe037a0d819 | null | 2004-01-01T00:01:00 | true | [O:1]([C:8]1[CH:9]=[C:10]([C:14]2[CH2:18][CH:17]([CH2:19][CH2:20][CH:21]=O)[O:16][N:15]=2)[CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:23]1([CH:29]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[N:30]2[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]2)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[CH:29]([N:30]1[CH2:35][CH2:34][N:33]([CH2:21][CH2:20][CH2:19][CH:17]2[O:16][N:15]=[C:14]([C:10]3[CH:11]=[CH:12][CH:13]=[C:8]([O:1][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)[CH:9]=3)[CH2:18]2)[CH2:32][CH2:31]1)([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1 | O=CCCC1CC(c2cccc(Oc3ccccc3)c2)=NO1 | c1ccc(C(c2ccccc2)N2CCNCC2)cc1 | null | CC(=O)O[BH-](OC(C)=O)OC(C)=O | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | null | null | 3-[3-(3-Phenoxyphenyl)-4,5-dihydroisoxazol-5-yl]propanal (27.1 mg, 0.087 mmol), 1-(diphenylmethyl)piperazine (20.0 mg, 0.078 mmol), molecular sieve (5 beads) and NaBH(OAc)3 (50.0 mg, 0.237 mmol) were reacted in 3 mL of methylene chloride for about 12 hr. With the following processes the same as in Example 1, 20.2 mg (53.3%) of the target compound was obtained. | c1ccc(Oc2cccc(C3=NOC(CCCN4CCN(C(c5ccccc5)c5ccccc5)CC4)C3)c2)cc1 | null | 48.7 | null |
202,033 | ord_dataset-19e5fc80c1554f4f8641c835e055f02b | null | 1990-01-01T00:01:00 | true | [OH:1][C:2]1[CH:18]=[CH:17][C:5]([O:6][CH2:7][CH2:8][CH2:9][CH2:10][C:11]([CH3:16])([CH3:15])[C:12]([NH2:14])=[O:13])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[Br:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30]Br>C(O)C>[Br:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][O:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][CH2:7][CH2:8][CH2:9][CH2:10][C:11]([CH3:15])([CH3:16])[C:12]([NH2:14])=[O:13])=[CH:17][CH:18]=1 | CC(C)(CCCCOc1ccc(O)cc1)C(N)=O | BrCCCCCBr | null | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | null | null | null | null | null | null | null | null | null | null | null | null | A mixture of 3.0 g 6-(4-hydroxyphenoxy)-2,2-dimethylhexanamide, 50 ml ethanol, 2.5 g potassium carbonate and 3.6 g 1,5-dibromopentane was heated under reflux overnight with stirring. The solvent was distilled off under reduced pressure, the residue was extracted with chloroform, the extract was washed with water and worked up as usual. The crude product thus obtained was purified by silica gel column chromatography, affording 2.90 g of 6-[p-(5-bromopentyloxy)phenoxy]-2,2-dimethylhexanamide. | CC(C)(CCCCOc1ccc(OCCCCCBr)cc1)C(N)=O | null | 60.7 | null |
1,621,651 | ord_dataset-35c51552812941cda45194a013d34bb9 | null | 2015-01-01T00:08:00 | true | [CH3:1]CN(CC)CC.[CH2:8]([O:15][N:16]1[C:22](=[O:23])[N:21]2[CH2:24][C@H:17]1[CH2:18][CH2:19][C@H:20]2[C:25]1[O:26][C:27]([N:30]2[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]2)=[N:28][N:29]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.CI>CN(C=O)C>[CH2:8]([O:15][N:16]1[C:22](=[O:23])[N:21]2[CH2:24][C@H:17]1[CH2:18][CH2:19][C@H:20]2[C:25]1[O:26][C:27]([N:30]2[CH2:35][CH2:34][N:33]([CH3:1])[CH2:32][CH2:31]2)=[N:28][N:29]=1)[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1 | O=C1N2C[C@@H](CC[C@H]2c2nnc(N3CCNCC3)o2)N1OCc1ccccc1 | CCN(CC)CC | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CI | CN(C)C=O | null | null | null | null | null | null | null | null | null | 25 | 6 | Et3N (631 μL, 4.5 mmol) was added to a solution of crude (2S,5R)-6-(benzyloxy)-2-(5-(piperazin-1-yl)-1,3,4-oxadiazol-2-yl)-1,6-diaza-bicyclo[3.2.1]octan-7-one (997 mg) in DMF (15 mL). Then, MeI (106 μL, 1.6 mmol) was slowly added at 0° C. The mixture was stirred at rt for 6 hrs then, the mixture was concentrated and purified by reverse phase column chromatography (gradient elution, 0 to 80% of acetonitrile in water) to give (2S,5R)-6-(benzyloxy)-2-(5-(4-methylpiperazin-1-yl)-1,3,4-oxadiazol-2-yl)-1,6-diaza-bicyclo[3.2.1]octan-7-one (202 mg, 34% for two steps) as a yellow solid. ESI-MS (EI+, m/z): 399.3 [M+H]+. | CN1CCN(c2nnc([C@@H]3CC[C@@H]4CN3C(=O)N4OCc3ccccc3)o2)CC1 | null | 19.5 | null |
1,607,308 | ord_dataset-9cecb3a8d3b9494191b28dcefea66af2 | null | 2015-01-01T00:07:00 | true | Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]([NH2:14])=[N:12][CH:13]=2)=[C:4]([F:15])[CH:3]=1.CC1(C)C(C)(C)[O:20][B:19](B2OC(C)(C)C(C)(C)O2)[O:18]1.CC([O-])=O.[K+].Cl>CCOC(C)=O.O1CCOCC1>[NH2:14][C:11]1[N:12]=[CH:13][C:8]([C:5]2[CH:6]=[CH:7][C:2]([B:19]([OH:20])[OH:18])=[CH:3][C:4]=2[F:15])=[CH:9][CH:10]=1 | Nc1ccc(-c2ccc(Cl)cc2F)cn1 | CC1(C)OB(B2OC(C)(C)C(C)(C)O2)OC1(C)C | null | CC(=O)[O-] | Cl | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOC(C)=O | C1COCCO1 | null | null | null | null | null | null | null | null | null | 80 | 0.33 | 5-(4-Chloro-2-fluorophenyl)pyridin-2-amine (2.0 g, 9.0 mmol), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (2.9 g, 11.0 mmol), chloro(2-dicyclohexyl-phosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) (0.14 g, 0.18 mmol), and KOAc (2.7 g, 27 mmol) were combined in a sealable reaction vessel under nitrogen, and then treated with anhydrous 1,4-dioxane (100 mL, sparged with nitrogen). The vessel was sealed and then heated at 80° Celsius for 16 hours. The mixture was cooled to rt, HCl (1 m, 50 mL) was added and the mixture stirred for 20 min. The mixture was then diluted with EtOAc (200 mL) and the aqueous phase was collected. The organic phase was extracted with 1 M HCl (2×75 mL). The combined aqueous phases were cooled in an icebath and the pH was adjusted to ca. 7 using solid sodium bicarbonate. The resulting precipitate was collected by filtration, washed well with water, and dried to provide the title compound (2.1 g, 98%). MS (CI): mass calcd. for C11H10BFN2O2, 232.08; m/z found, 233.1 [M+H]+. 1H NMR (500 MHz, DMSO-d6) δ 8.29-8.20 (s, 2H), 8.18-8.13 (s, 1H), 7.80-7.72 (m, 1H), 7.69-7.63 (m, 1H), 7.63-7.57 (m, 1H), 7.51-7.44 (m, 1H), 6.84-6.57 (m, 3H). | Nc1ccc(-c2ccc(B(O)O)cc2F)cn1 | null | 100.6 | null |
349,308 | ord_dataset-66f304805e5d47fc8d3c722b1bd8dfa2 | null | 1996-01-01T00:12:00 | true | [F:1][C:2]1[C:3]([CH3:27])=[C:4]2[C:9](=[CH:10][C:11]=1F)[N:8]([C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=1[F:20])[CH:7]=[C:6]([C:21]([O:23]CC)=[O:22])[C:5]2=[O:26].[NH:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1>C(#N)C>[F:1][C:2]1[C:3]([CH3:27])=[C:4]2[C:9](=[CH:10][C:11]=1[N:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1)[N:8]([C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=1[F:20])[CH:7]=[C:6]([C:21]([OH:23])=[O:22])[C:5]2=[O:26] | CCOC(=O)c1cn(-c2ccc(F)cc2F)c2cc(F)c(F)c(C)c2c1=O | C1CNCCN1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC#N | null | null | null | null | null | null | null | null | null | null | null | null | A solution of 0.76 g (2.00 mmol) of ethyl 6,7-difluoro-1-(2,4-difluorophenyl)-1,4-dihydro-5-methyl-4-oxo-3-quinolinecarboxylate, 0.69 g (8.00 mmol) of anhydrous piperazine, and 30 mL of acetonitrile was refluxed for 18 hours, cooled, and concentrated. The residue was dissolved in 20 mL 6N hydrochloric acid and refluxed for 3 hours. The suspension was cooled, concentrated by half and filtered, and the solids were washed with water. The crude product was suspended in water which was made basic (pH 12), and the resulting solution was filtered and neutralized to pH 6.8. The precipitate which formed was filtered, washed with water, and dried to give 0.58 g of the title compound, mp 198°-200° C. | Cc1c(F)c(N2CCNCC2)cc2c1c(=O)c(C(=O)O)cn2-c1ccc(F)cc1F | null | 69.5 | null |
1,184,865 | ord_dataset-9cd817a75dfc4fe7ad19d4232772d5ff | null | 2012-01-01T00:07:00 | true | CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[C:22]([C:24]1[CH:25]=[C:26]([CH:30]=[CH:31][C:32]=1[O:33][CH:34]([CH3:36])[CH3:35])[C:27]([OH:29])=O)#[N:23].O[NH:38][C:39]([C:41]1[CH:42]=[C:43]2[C:47](=[CH:48][CH:49]=1)[NH:46][C:45]([CH2:50][OH:51])=[CH:44]2)=[NH:40]>CN(C=O)C.CCOC(C)=O>[OH:51][CH2:50][C:45]1[NH:46][C:47]2[C:43]([CH:44]=1)=[CH:42][C:41]([C:39]1[N:40]=[C:27]([C:26]3[CH:30]=[CH:31][C:32]([O:33][CH:34]([CH3:36])[CH3:35])=[C:24]([CH:25]=3)[C:22]#[N:23])[O:29][N:38]=1)=[CH:49][CH:48]=2 | N=C(NO)c1ccc2[nH]c(CO)cc2c1 | CC(C)Oc1ccc(C(=O)O)cc1C#N | null | CCN=C=NCCCN(C)C | On1nnc2ccccc21 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | CCOC(C)=O | null | null | null | null | null | null | null | null | null | 80 | 0.25 | EDCI (144 mg) and HOBT (104 mg) were added to a solution of 3-cyano-4-[(1-methylethyl)oxy]benzoic acid (can be prepared as described on WO2005/58848, 144 mg) in DMF (5 mL) at RT. The resulting solution was stirred for 15 min. N-Hydroxy-2-(hydroxymethyl)-1H-indole-5-carboximidamide (D25) (144 mg) was added and the reaction mixture was stirred at RT for 1 hour. The reaction mixture was heated to 80° C. and stirred at that temperature for 4 hours. EtOAc (50 mL) was added and the organic solution was washed with water (50 mL), saturated aqueous sodium bicarbonate solution (50 mL) and water (50 mL). The organic fraction was dried over anhydrous magnesium sulfate. The dried solution was concentrated. The residue was recrystallized from EtOAc/ether to afford 5-{3-[2-(hydroxymethyl)-1H-indol-5-yl]-1,2,4-oxadiazol-5-yl}-2-[(1-methylethyl)oxy]benzonitrile (E12) (70 mg) as a light brown solid. δH (DMSO-d6, 400 MHz): 1.39 (6H, d), 4.65 (2H, d), 4.99 (1H, m), 5.36 (1H, t), 6.46 (1H, s), 7.49 (1H, d), 7.56 (1H, d), 7.79 (1H, dd), 8.28 (1H, dd), 8.42 (1H, d), 8.52 (1H, d), 11.43 (1H, s). MS (ES): C21H18N4O3 requires 374; found 375.0 (M+H+). | CC(C)Oc1ccc(-c2nc(-c3ccc4[nH]c(CO)cc4c3)no2)cc1C#N | null | 26.6 | null |
1,246,519 | ord_dataset-c544c0c663f54dbea4ddb52ddde7934e | null | 2013-01-01T00:01:00 | true | [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[C:15]([CH3:16])=[C:14]([CH3:17])[C:13]([N:18]4[CH2:23][CH2:22][N:21](C(OC(C)(C)C)=O)[CH2:20][CH2:19]4)=[N:12][N:11]3[C:31]=2[C:32]2[CH:37]=[CH:36][N:35]=[CH:34][CH:33]=2)=[CH:4][CH:3]=1.FC(F)(F)C(O)=O>ClCCl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[C:15]([CH3:16])=[C:14]([CH3:17])[C:13]([N:18]4[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]4)=[N:12][N:11]3[C:31]=2[C:32]2[CH:33]=[CH:34][N:35]=[CH:36][CH:37]=2)=[CH:4][CH:3]=1 | Cc1c(N2CCN(C(=O)OC(C)(C)C)CC2)nn2c(-c3ccncc3)c(-c3ccc(F)cc3)nc2c1C | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O=C(O)C(F)(F)F | ClCCl | null | null | null | null | null | null | null | null | null | 25 | 4 | To a solution of 0.43 g (0.86 mmol) of tert-butyl 4-[2-(4-fluorophenyl)-7,8-dimethyl-3-pyrid-4-ylimidazo[1,2-b]pyridazin-6-yl]piperazine-1-carboxylate in 5 mL of dichloromethane at 0° C. is added dropwise 0.64 mL (8.6 mmol) of trifluoroacetic acid. After stirring for 4 hours at room temperature, a further 0.64 mL (8.6 mmol) of trifluoroacetic acid is added and the reaction mixture is left for 18 hours. The solvent is then removed under reduced pressure and the residue is taken up in water. The resulting aqueous phase is washed with ether and then basified by addition of aqueous sodium hydrogen carbonate solution. The product is extracted with dichloromethane, the organic phase is dried over sodium sulfate and filtered, and the solvent is evaporated off to give 0.285 g of a white powder. | Cc1c(N2CCNCC2)nn2c(-c3ccncc3)c(-c3ccc(F)cc3)nc2c1C | null | 82.3 | null |
1,399,550 | ord_dataset-12dc3bd21bcf44d09e5b4249afe15161 | null | 2014-01-01T00:02:00 | true | [C:1](O)(=[O:3])[CH3:2].[NH2:5][CH2:6][C@@H:7]1[O:11][C:10](=[O:12])[N:9]([C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)=[C:15]([F:25])[CH:14]=2)[CH2:8]1.C(OC(=O)C)(=O)C>O>[CH3:2][C:1]([NH:5][CH2:6][C@@H:7]1[O:11][C:10](=[O:12])[N:9]([C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH2:20][CH2:21][O:22][CH2:23][CH2:24]3)=[C:15]([F:25])[CH:14]=2)[CH2:8]1)=[O:3] | NC[C@H]1CN(c2ccc(N3CCOCC3)c(F)c2)C(=O)O1 | CC(=O)O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CC(=O)OC(C)=O | null | null | null | null | null | null | null | null | null | 50 | 2 | (S)-5-(aminomethyl)-3-(3-fluoro-4-morpholinophenyl)oxazolidin-2-one acetate (3.5 g, 10 mmol) was dissolved in 20 mL of water. The solution was heated to 50° C. and then acetic anhydride (0.72 g, 12 mmol) was added dropwise and stirred at 50° C. for 2 hours. The mixture was cooled down to 0° C. to crystallize, filtered, washed with water, dried and recrystallized with ethyl acetate to provide 3.0 g of Linezolid in 88% yield. | CC(=O)NC[C@H]1CN(c2ccc(N3CCOCC3)c(F)c2)C(=O)O1 | null | 88.9 | null |
801,704 | ord_dataset-56a22bc0c3b14f87b9aa3f2fc6488ee7 | null | 2007-01-01T00:12:00 | true | [OH:1][N:2]1[C:6](=[O:7])[C:5]2=[CH:8][CH:9]=[CH:10][CH:11]=[C:4]2[C:3]1=[O:12].[C:13]1(B(O)O)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.N1C=CC=CC=1>[Cu]Cl.ClCCCl>[O:1]([N:2]1[C:3](=[O:12])[C:4]2=[CH:11][CH:10]=[CH:9][CH:8]=[C:5]2[C:6]1=[O:7])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1 | OB(O)c1ccccc1 | O=C1c2ccccc2C(=O)N1O | null | Cl[Cu] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | c1ccncc1 | ClCCCl | null | null | null | null | null | null | null | null | null | 25 | null | A 20 mL scintillation vial was charged with N-hydroxyphthalimide (163 mg, 1.0 mmol), copper (I) chloride (99 mg, 1.0 mmol), freshly activated 4 Å molecular sieves (˜250 mg), and phenylboronic acid (244 mg, 2.0 mmol). 1,2-Dichloroethane (5 mL) was added followed by pyridine (90 μL, 1.1 mmol), resulting in a light brown suspension. The cap was loosely applied such that the reaction suspension was open to air and stirred at room temperature until completion as detected by analytical RP-HPLC (mixture color turned from brown to emerald green as the reaction proceeded). Upon completion (˜48 h), the mixture was adsorbed onto silica gel and concentrated to a powder. Flash chromatographic purification over silica (25% EtOAc in hexanes) afforded N-phenoxyphthalimide 9 as a white solid (216 mg, 90%); see below for characterization data. | O=C1c2ccccc2C(=O)N1Oc1ccccc1 | null | 90.3 | null |
263,197 | ord_dataset-a7bd0db0684c464bb02ff6a36065fee3 | null | 1993-01-01T00:03:00 | true | [CH2:1]([C:8]([C:21]#[N:22])([CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:9]([O:11]CC)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[K+]>O.C(O)C.O>[CH2:14]([C:8]([C:21]#[N:22])([CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:9]([OH:11])=[O:10])[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1 | CCOC(=O)C(C#N)(Cc1ccccc1)Cc1ccccc1 | null | null | [K+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | O | null | null | null | null | null | null | null | null | null | null | null | Ethyl 2-benzyl-2-cyano-3-phenylpropionate (3.20 g, 11 mmol) was saponified at room temperature overnight with potassium hydroxide (6.17 g, 0.11 mol) in 10% water/ethanol. The mixture was diluted with water (200 mL) and extracted with hexane (2×50 mL). The aqueous layer was acidified with 1M phosphoric acid and extracted with methylene chloride (4×100 mL). The combined organic extracts were dried over magnesium sulfate and freed of solvent to afford 2-benzyl-2-cyano-3-phenylpropionic acid (2.94 g, 11 mmol) as a colorless solid: 1H NMR (CDCl3, 300 MHz) δ 7.34 (br s, 10 H), 3.24 (dd, J=13.5, 57 Hz); mass spectrum m/e 283 (M+NH4+). | N#CC(Cc1ccccc1)(Cc1ccccc1)C(=O)O | null | 100 | null |
1,049,954 | ord_dataset-dd320ded4b3f4764af39de99491533f7 | null | 2011-01-01T00:04:00 | true | C(OC([O:8][NH:9][C:10]([C:12]1[CH:13]=[N:14][C:15]([N:18]2[CH2:23][CH:22]3[CH:20]([CH:21]3[CH2:24][NH:25][CH2:26][C:27]3[CH:36]=[CH:35][C:34]4[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=4)[CH:28]=3)[CH2:19]2)=[N:16][CH:17]=1)=[O:11])C)C(C)C.Cl.O1CCOCC1>C(Cl)Cl>[OH:8][NH:9][C:10]([C:12]1[CH:13]=[N:14][C:15]([N:18]2[CH2:23][CH:22]3[CH:20]([CH:21]3[CH2:24][NH:25][CH2:26][C:27]3[CH:36]=[CH:35][C:34]4[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=4)[CH:28]=3)[CH2:19]2)=[N:16][CH:17]=1)=[O:11] | CC(C)COC(C)ONC(=O)c1cnc(N2CC3C(CNCc4ccc5ccccc5c4)C3C2)nc1 | 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 | 0.17 | N-(1-Isobutoxyethoxy) 2-(6-{[(naphthalen-2-ylmethyl)amino]methyl}-3-azabicyclo[3.1.0]hex-3-yl)pyrimidine-5-carboxamide (43 mg, 0.09 mmol) was stirred in DCM (2 ml) at r.t. under N2 and 4M HCl in dioxane (45 μl, 0.18 mmol) was added. This immediately caused a solid to precipitate. The reaction was allowed to stir for 10 min and then the solvent was removed in vacuo to give the title compound as a white solid (16 mg, 50%). LCMS purity 98%, m/z 390 [M+H]+, 1H NMR (300 MHz, d6-DMSO) δ: 1.91 (2H, m), 2.50 (1H, m), 2.99 (2H, m), 3.55 (2H, m), 3.88 (2H, d, J=11.7 Hz), 4.34 (2H, m), 7.58 (2H, m), 7.68 (1H, m), 7.95 (2H, m), 8.03 (2H, m), 8.66 (2H, s), 9.11 (2H, br s), 11.07 (1H, br s). | O=C(NO)c1cnc(N2CC3C(CNCc4ccc5ccccc5c4)C3C2)nc1 | null | 45.6 | null |
979,751 | ord_dataset-f886e51ba1484c76a94bce1482f1eab9 | null | 2010-01-01T00:07:00 | true | Cl[C:2]1[C:11]2[C:6](=[N:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1.[NH2:12][C:13]1[CH:18]=[C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=2)[CH:16]=[CH:15][C:14]=1[S:28][C:29]1[CH:34]=[CH:33][C:32]([OH:35])=[CH:31][CH:30]=1>>[Cl:27][C:24]1[CH:25]=[CH:26][C:21]([CH2:20][O:19][C:17]2[CH:16]=[CH:15][C:14]([S:28][C:29]3[CH:34]=[CH:33][C:32]([OH:35])=[CH:31][CH:30]=3)=[C:13]([NH:12][C:2]3[C:11]4[C:6](=[N:7][CH:8]=[CH:9][CH:10]=4)[N:5]=[CH:4][CH:3]=3)[CH:18]=2)=[CH:22][CH:23]=1 | Nc1cc(OCc2ccc(Cl)cc2)ccc1Sc1ccc(O)cc1 | Clc1ccnc2ncccc12 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The product from Example 16c (50 mg, 0.30 mmol) was reacted with the product from Example 143a (107 mg, 0.30 mmol) for 24 h following the procedure from Example 1g giving the crude title compound which was purified by HPLC with TFA providing the product as a trifluoroacetic acid (50 mg, 27%). 1H NMR (300 MHz, DMSO-d6) δ ppm: 5.14 (s, 2 H) 6.31 (d, J=7.36 Hz, 1 H) 6.64 (d, J=8.82 Hz, 2 H) 7.05-7.40 (m, J=8.46 Hz, 4 H) 7.46 (m, J=5.52 Hz, 3 H) 7.93 (m, J=4.41 Hz, 1 H) 8.48 (d, J=6.98 Hz, 1 H) 9.17 (m, J=1.47 Hz, J=5.88 Hz, 3 H) 9.79 (s,1 H) 11.15 (br s, 1 H) 14.54 (br s, 1 H); MS (ESI+) m/z,486 (M+H−TFA)+; (ESI−) m/z,484 (M−H−TFA)−. | Oc1ccc(Sc2ccc(OCc3ccc(Cl)cc3)cc2Nc2ccnc3ncccc23)cc1 | null | null | null |
1,347,066 | ord_dataset-6034127657614f02860ed057b62b882e | null | 2013-01-01T00:10:00 | true | [OH-].[Na+].C([O:5][C:6](=[O:26])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][N:13]1[CH:17]=[CH:16][C:15]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[O:24][CH3:25])=[N:14]1)C>CO>[CH3:25][O:24][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[C:15]1[CH:16]=[CH:17][N:13]([CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][C:6]([OH:26])=[O:5])[N:14]=1 | CCOC(=O)CCCCCCn1ccc(-c2ccccc2OC)n1 | null | null | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | null | 8 | Add 2 N sodium hydroxide (20 mL) to a solution of 7-[3-(2-Methoxyphenyl)pyrazol-1-yl]heptanoic acid ethyl ester (3.75 g, 11.4 mmol) in methanol (40 mL) at room temperature under nitrogen and stir the mixture for 8 hours. Remove the solvent under reduced pressure, dilute the residue with water (100 mL), acidify to pH 3 with 1 N HCl, extract with ethyl acetate (200 mL), and dry over sodium sulfate. Remove the solvent under reduced pressure to provide 7-[3-(2-methoxyphenyl)pyrazol-1-yl]heptanoic acid (3.06 g, 89%). APCI mass spectrum m/z 303 [C17H22N2O3+H]+. | COc1ccccc1-c1ccn(CCCCCCC(=O)O)n1 | null | 88.8 | null |
642,430 | ord_dataset-ce71a906ea9c4399a2014cbaaff88c8f | null | 2004-01-01T00:07:00 | true | C([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([C:13]([O:15][CH3:16])=[O:14])[CH:11]=2)[C:6](=[C:17](OCC)[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:5]1=[O:27])(=O)C.[CH3:28][N:29]([CH3:44])[CH2:30][CH2:31][N:32]([C:37]1[CH:43]=[CH:42][C:40]([NH2:41])=[CH:39][CH:38]=1)[C:33](=[O:36])[CH2:34][CH3:35]>>[CH3:44][N:29]([CH3:28])[CH2:30][CH2:31][N:32]([C:37]1[CH:38]=[CH:39][C:40]([NH:41]/[C:17](=[C:6]2\[C:5](=[O:27])[NH:4][C:12]3[C:7]\2=[CH:8][CH:9]=[C:10]([C:13]([O:15][CH3:16])=[O:14])[CH:11]=3)/[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:42][CH:43]=1)[C:33](=[O:36])[CH2:34][CH3:35] | CCC(=O)N(CCN(C)C)c1ccc(N)cc1 | CCOC(=C1C(=O)N(C(C)=O)c2cc(C(=O)OC)ccc21)c1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Prepared from 1-acetyl-3-(1-ethoxy-1-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(N-(2-dimethylamino-ethyl)-N-propionyl-amino)-aniline Rf value: 0.5 (silica gel, methylene chloride/methanol=9:1) C30H32N4O4 | CCC(=O)N(CCN(C)C)c1ccc(N/C(=C2\C(=O)Nc3cc(C(=O)OC)ccc32)c2ccccc2)cc1 | null | null | null |
1,322,932 | ord_dataset-cfad8b3f00044bcda60a96b019f09872 | null | 2013-01-01T00:08:00 | true | Cl.[NH2:2][CH2:3][C:4]1[C:13](=[O:14])[C:12]2[C:7](=[N:8][C:9]([C:15]([F:18])([F:17])[F:16])=[CH:10][CH:11]=2)[N:6]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:5]=1[C:25]([O:27][CH3:28])=[O:26].[Cl:29][C:30]1[CH:31]=[C:32]([CH:36]=[CH:37][C:38]=1[Cl:39])[C:33](O)=[O:34]>>[CH3:28][O:27][C:25]([C:5]1[N:6]([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:7]2[C:12]([C:13](=[O:14])[C:4]=1[CH2:3][NH:2][C:33](=[O:34])[C:32]1[CH:36]=[CH:37][C:38]([Cl:39])=[C:30]([Cl:29])[CH:31]=1)=[CH:11][CH:10]=[C:9]([C:15]([F:16])([F:17])[F:18])[N:8]=2)=[O:26] | O=C(O)c1ccc(Cl)c(Cl)c1 | COC(=O)c1c(CN)c(=O)c2ccc(C(F)(F)F)nc2n1-c1ccccc1 | 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 | 3-[(3,4-Dichloro-benzoylamino)-methyl]-4-oxo-1-phenyl-7-trifluoromethyl-1,4-dihydro-[1,8]-naphthyridine-2-carboxylic acid methyl ester was prepared starting from intermediate J and 3,4-dichlorobenzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.90 (d, J=8.06 Hz, 1H) 8.80 (t, J=4.63 Hz, 1H) 8.04 (d, J=1.81 Hz, 1H) 7.97 (d, J=8.06 Hz, 1H) 7.67-7.83 (m, 2H) 7.51-7.60 (m, 3H) 7.35-7.47 (m, 2H) 4.44 (d, J=4.83 Hz, 2H) 3.39 (s, 3H). MS calcd. for C25H16Cl2F3N3O4 [(M+H)+] 549.0, obsd. 549.9. | COC(=O)c1c(CNC(=O)c2ccc(Cl)c(Cl)c2)c(=O)c2ccc(C(F)(F)F)nc2n1-c1ccccc1 | null | null | null |
1,730,273 | ord_dataset-36057d699ac5449e9c37eb99abf78b03 | null | 2016-01-01T00:05:00 | true | [NH2:1][C@@H:2]([C:6]([OH:8])=[O:7])[C@H:3]([CH3:5])[OH:4].C([O-])(O)=O.[Na+].[C:14]1([CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][O:26][C:27](N2C=CC=CC2=O)=[O:28])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>O.C1COCC1>[OH:4][C@@H:3]([CH3:5])[C@@H:2]([NH:1][C:27]([O:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)=[O:28])[C:6]([OH:8])=[O:7] | C[C@H](O)[C@@H](N)C(=O)O | O=C(OCCCCCCc1ccccc1)n1ccccc1=O | null | O=C([O-])O | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | 15 | To a stirred mixture of D-threonine (0.12 g, 1.0 mmol) and NaHCO3 (0.13 g, 1.5 mmol) in H2O (3.5 mL), the crude mixture containing 6-phenylhexyl-2-pyridyl-carbonate and 6-phenylhexyl-2-oxopyridine 1-carboxylate (0.45 g, 1.5 mmol) in THF (3.5 mL) was added. After 15 h at rt, the crude mixture was rotary evaporated to remove the organics and subsequently extracted with Et2O (3×5 mL). The aqueous phase was acidified with 2M HCl solution to pH 2-3 and subsequently extracted with AcOEt (3×10 mL). The organic fraction was dried over Na2SO4, filtered and concentrated to dryness to afford the title compound (0.25 g, 78%) as transparent oil, which was used in the next step without further purification. MS (ESI) m/z: 324 [M−H]+; (ESI) m/z: 322 [M−H]−. 1H NMR (DMSO-d6): δ 1.08 (d, J=6.4 Hz, 3H), 1.24-1.40 (m, 4H), 1.46-1.63 (m, 4H), 2.56 (t, J=7.6 Hz, 2H), 3.88-3.99 (m, 3H), 4.00-4.12 (m, 1H), 6.67 (d, J=9.0 Hz, 1H), 7.13-7.21 (m, 3H), 7.22-7.31 (m, 2H), 12.40 (br s, 1H). | C[C@H](O)[C@@H](NC(=O)OCCCCCCc1ccccc1)C(=O)O | null | 77.3 | null |
712,203 | ord_dataset-c8a367b56b4f406b878f51867b157d19 | null | 2006-01-01T00:06:00 | true | [CH:1]1([NH2:7])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl:8][C:9]1[CH:14]=[C:13]([Cl:15])[CH:12]=[CH:11][C:10]=1[C:16]1[N:17]=[C:18]([C:30](OCC)=[O:31])[N:19]([CH3:29])[C:20]=1[C:21]1[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:22]=1[Cl:28]>>[CH:1]1([NH:7][C:30]([C:18]2[N:19]([CH3:29])[C:20]([C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:22]=3[Cl:28])=[C:16]([C:10]3[CH:11]=[CH:12][C:13]([Cl:15])=[CH:14][C:9]=3[Cl:8])[N:17]=2)=[O:31])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1 | CCOC(=O)c1nc(-c2ccc(Cl)cc2Cl)c(-c2ccc(Cl)cc2Cl)n1C | NC1CCCCC1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Using essentially the same procedure as Example 30, Step E, but using cyclohexylamine (1 mL), ethyl 4,5-di-(2,4-dichlorophenyl)-1-methylimidazole-2-carboxylate (10 mg, 0.022 mmol) from Example 30, Step D was converted to the title compound. HPLC/MS: 496 (M+1), 498 (100%, M+3), 500 (M+5); Rt=5.04 min. | Cn1c(C(=O)NC2CCCCC2)nc(-c2ccc(Cl)cc2Cl)c1-c1ccc(Cl)cc1Cl | null | null | null |
302,279 | ord_dataset-bfcf5a01f1a04ec585ba3f28cb93c8c9 | null | 1995-01-01T00:01:00 | true | [C:1]1([N:7]=[C:8]=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[F:10][C:11]1[CH:29]=[CH:28][C:14]2[C:15]([CH:18]3[CH2:23][CH2:22][N:21]([CH2:24][CH2:25][CH2:26][OH:27])[CH2:20][CH2:19]3)=[N:16][O:17][C:13]=2[CH:12]=1.[ClH:30]>C1(C)C=CC=CC=1.CCOCC>[ClH:30].[F:10][C:11]1[CH:29]=[CH:28][C:14]2[C:15]([CH:18]3[CH2:23][CH2:22][N:21]([CH2:24][CH2:25][CH2:26][O:27][C:8](=[O:9])[NH:7][C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)[CH2:20][CH2:19]3)=[N:16][O:17][C:13]=2[CH:12]=1 | O=C=Nc1ccccc1 | OCCCN1CCC(c2noc3cc(F)ccc23)CC1 | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Cc1ccccc1 | CCOCC | null | null | null | null | null | null | null | null | null | 25 | null | Phenylisocyanate (0.36 g, 3 mmol) and 3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidino]propanol (0.3 g, 1.1 mmol) was refluxed in toluene (25 ml) for 6 h. The mixture was cooled to room temperature and hydrochloric acid in ether was added. The resulting precipitate was recrystallized from ethanol/ether and isopropanol/ether to give 180 mg of the title compound as white crystals. M.p. 204.5°-205.5° C. MS (70 eV): m/z 397 (39%, M+), 278 (4), 259 (26), 233 (50), 178 (28), 96 (100). | O=C(Nc1ccccc1)OCCCN1CCC(c2noc3cc(F)ccc23)CC1 | null | null | null |
949,386 | ord_dataset-3feb2a95f66e4706a4a50c977ccd9bf8 | null | 2010-01-01T00:04:00 | true | [O:1]=[C:2]1[CH2:10][C:9]2[C:4](=[CH:5][C:6]([C:11]([C:13]3[CH:14]=[C:15]([NH:19][C:20](=[O:22])[CH3:21])[CH:16]=[CH:17][CH:18]=3)=[O:12])=[CH:7][CH:8]=2)[NH:3]1.[CH:23](OCC)=[O:24].[O-]CC.[Na+].Cl>C(O)C>[OH:24][CH:23]=[C:10]1[C:9]2[C:4](=[CH:5][C:6]([C:11]([C:13]3[CH:14]=[C:15]([NH:19][C:20](=[O:22])[CH3:21])[CH:16]=[CH:17][CH:18]=3)=[O:12])=[CH:7][CH:8]=2)[NH:3][C:2]1=[O:1] | CC(=O)Nc1cccc(C(=O)c2ccc3c(c2)NC(=O)C3)c1 | CCOC=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 | 78 | null | N-[3-(2-Oxo-2,3-dihydro-1H-indole-6-carbonyl)-phenyl]-acetamide (0.957 g, 3.25 mmol) and ethyl formate (0.781 mL, 9.75 mmol) were dissolved in anhydrous ethanol (6.50 mL). The resulting solution was treated in dropwise fashion with a 21 wt % solution of sodium ethoxide in ethanol (6.07 mL, 16.26 mmol). This reaction mixture was heated at 78° C. for 1 h, producing a black oil. Subsequently, the reaction mixture was cooled to room temperature, and then the reaction pH was adjusted to pH 1 with dropwise addition of 1M HCl(aq) causing the formation of a pale orange precipitate. The suspension was filtered yielding an orange solid as the pure N-[3-(3-Hydroxymethylene-2-oxo-2,3-dihydro-1H-indole-6-carbonyl)-phenyl]-acetamide (0.752 g, 2.33 mmol, 71%). | CC(=O)Nc1cccc(C(=O)c2ccc3c(c2)NC(=O)C3=CO)c1 | null | 71.7 | null |
363,867 | ord_dataset-c2ad1656a3ca4d08888ffb6e3f3a2742 | null | 1997-01-01T00:05:00 | true | C[O:2][C:3](=[O:24])[C@@H:4]1[CH2:8][CH2:7][CH2:6][N:5]1[CH:9]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C@@H:10]1[C@@H:14]([CH2:15][CH3:16])[CH2:13][CH2:12][NH:11]1.[OH-].[Na+].Cl>CO>[C:20]([O:19][C:17]([CH:9]([C@@H:10]1[C@@H:14]([CH2:15][CH3:16])[CH2:13][CH2:12][NH:11]1)[N:5]1[CH2:6][CH2:7][CH2:8][C@H:4]1[C:3]([OH:24])=[O:2])=[O:18])([CH3:23])([CH3:22])[CH3:21] | CC[C@H]1CCN[C@@H]1C(C(=O)OC(C)(C)C)N1CCC[C@H]1C(=O)OC | null | 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 | 0 | 3 | N-[(tert-Butyloxy)carbonyl-3(S)-ethylpyrrolidin-2(S)-ylmethyl]-proline methyl ester 0.081 g, 0.238 mmol) was dissolved in CH3OH (2 mL), cooled to 0° C. and treated with 1N NaOH solution (0.952 mL, 0.952 mmol). After stirring at 23° C. for 3 h, the solution was neutralized with 1N HCl (0.952 mL, 0.952 mmol), concentrated to remove the CH3OH, then lyophilized and the residue used as is. | CC[C@H]1CCN[C@@H]1C(C(=O)OC(C)(C)C)N1CCC[C@H]1C(=O)O | null | null | null |
702,529 | ord_dataset-c408dfed796e4354b61e312e67f7143f | null | 2006-01-01T00:04:00 | true | C(=O)([O-])[O-].[K+].[K+].[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([OH:30])[CH:25]=2)=[O:21])[CH2:16][CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8].Br[CH2:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>CC(C)=O>[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([O:30][CH2:32][CH2:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[CH:25]=2)=[O:21])[CH2:16][CH2:15]1)=[O:13])([CH3:10])([CH3:8])[CH3:9] | CC(C)(C)OC(=O)N1CCN(C(=O)OCc2cccc(O)c2)CC1 | BrCCc1ccccc1 | null | O=C([O-])[O-] | [K+] | 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 | 25 | null | potassium carbonate (0.072 g, 0.52 mmol) was added to a solution of piperazine-1,4-dicarboxylic acid (3-hydroxy)benzyl ester tert-butyl ester (0.16 g, 0.48 mmol) in acetone (5 mL) at 0° C. and the reaction mixture was stirred at 0° C. for 30 min. (2-Bromoethyl)-benzene (0.097 g, 0.52 mmol) was added and the reaction mixture was allowed to warm to room temperature and then heated under reflux for 24 h. After cooling, the reaction mixture was concentrated in vacuo and the residue was partitioned between water (20 mL) and ethyl acetate (20 mL). The organic phase was separated, washed with saturated brine (25 mL), dried (MgSO4) and concentrated in vacuo to give an oil which was purified by column chromatography [SiO2; heptane-ethyl acetate (3:1)] to yield the title compound (0.10 g, 48%) as a colourless oil. 1H-NMR (400 MHz, CDCl3): 1.46 (9H, s), 3.10 (2H, t, J=7.0 Hz), 3.40 (4H, m), 3.46 (4H, m), 4.18 (2H, t, J=7.0 Hz), 5.09 (2H, s), 6.84 (1H, m), 6.88 (1H, m), 6.91 (1H, m) and 7.22–7.34 (6H, m). | CC(C)(C)OC(=O)N1CCN(C(=O)OCc2cccc(OCCc3ccccc3)c2)CC1 | null | 47.3 | null |
277,447 | ord_dataset-ad17798fcea64e26ba91604fca520090 | null | 1993-01-01T00:10:00 | true | [C:1]([Si:5]([CH2:8]Cl)([CH3:7])[CH3:6])([CH3:4])([CH3:3])[CH3:2].[I-:10].[Na+]>CC(C)=O>[C:1]([Si:5]([CH2:8][I:10])([CH3:7])[CH3:6])([CH3:4])([CH3:3])[CH3:2] | [I-] | CC(C)(C)[Si](C)(C)CCl | null | [Na+] | 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 | null | 24 | t-Butyl(chloromethyl)dimethylsilane [Makoto Kumada, Mitsuo Ishikawa, Sajiro Meada and Katsuyata Ikura, J. Organometal. Chem. 2, 146, (1964)] (16.4 g, 0.1 mmol) and sodium iodide (60 g, 0.4 mmol) in acetone (500 ml) are refluxed with stirring during 24 hours. The reaction mixture is cooled, filtered and the solvent is evaporated under reduced pressure. The residue is dissolved in ether and washed with water. The organic layer is dried over sodium sulfate, filtered and concentrated under reduced pressure to afford t-butyl(iodomethyl)dimethylsilane (20.9 g, 80%) as a slightly yellow oil. | CC(C)(C)[Si](C)(C)CI | null | 81,576.9 | null |
1,452,030 | ord_dataset-a86112d52cd54525a5e36d41f18aced2 | null | 2014-01-01T00:07:00 | true | Cl[C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([NH2:9])[N:3]=1.[Cl:10][C:11]1[CH:12]=[C:13](B(O)O)[C:14]([F:17])=[N:15][CH:16]=1.C([O-])(=O)C.[K+]>CCO.O>[Cl:10][C:11]1[CH:12]=[C:13]([C:2]2[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([NH2:9])[N:3]=2)[C:14]([F:17])=[N:15][CH:16]=1 | OB(O)c1cc(Cl)cnc1F | Cc1nc(N)nc(Cl)n1 | null | CC(=O)[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | O | null | null | null | null | null | null | null | null | null | 100 | null | To a 20 mL microwave reaction tube was added 4-chloro-6-methyl-1,3,5-triazin-2-amine (Example 9, 1.00 g, 6.94 mmol), 5-chloro-2-fluoropyridin-3-ylboronic acid (Combi-Blocks, 1.62 g, 9.22 mmol), potassium acetate (Aldrich, 2.07 g, 21.1 mmol) and Am-Phos (Aldrich, 0.247 g, 0.349 mmol) in EtOH (12 mL) and water (1.2 mL). The mixture was degassed by bubbling argon through for 5 min. The tube was heated in an microwave reactor (Biotage) at 100° C. for 20 min. The reaction mixture was partitioned between water (100 mL) and 25% IPA in chloroform with 1% NH4OH (60 mL). The aqueous phase was extracted with 25% IPA in chloroform with 1% NH4OH (2×50 mL). The combined organic phases were washed with saturated aqueous sodium chloride (40 mL). The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo. Adding DCM to the residue resulted in precipitate formation. The solid was collected via filtration and washed with MeOH to afford 4-(5-chloro-2-fluoropyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (0.937 g) as a light yellow powder. The filtrate and the wash were combined and concentrated, then purified by column chromatography (eluent: iPrOH (w/10% NH4OH) in CHCl3 0.25% to 6.25%) followed by washing with MeOH to afford additional product (0.149 g) as a white solid. The total yield is 1.08 g (65%). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.54 (dd, J=8.02, 2.74 Hz, 1H) 8.46-8.51 (m, 1H) 7.73 (s, 2H) 2.37 (s, 3H). m/z (ESI, positive ion) m/z: 240.1 (M+H)+. | Cc1nc(N)nc(-c2cc(Cl)cnc2F)n1 | null | 56.3 | null |
1,363,750 | ord_dataset-d932d1d683704a8bad3d064bcb197acc | null | 2013-01-01T00:11:00 | true | [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH2:10][CH:11]([CH3:16])[C:12](=[O:15])[NH:13][N:14]=2)=[CH:5][CH:4]=1.CI.[C:19]([O-])([O-])=O.[Cs+].[Cs+]>>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[C:11]([CH3:16])[C:12](=[O:15])[N:13]([CH3:19])[N:14]=2)=[CH:5][CH:4]=1 | O=C([O-])[O-] | COc1ccc(C2=NNC(=O)C(C)C2)cc1 | null | [Cs+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CI | null | null | null | null | null | null | null | null | null | null | null | null | The product of step 2 (6-(4-methoxy-phenyl)-2,4-dimethyl-2H-pyridazin-3-one) was prepared as described for example 22 step 2 using 6-(4-methoxy-phenyl)-4-methyl-4,5-dihydro-2H-pyridazin-3-one, MeI and Cs2CO3. | COc1ccc(-c2cc(C)c(=O)n(C)n2)cc1 | null | null | null |
1,403,102 | ord_dataset-7456bda2326f4bebaa874a5474d4cc0d | null | 2014-01-01T00:03:00 | true | [CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([CH:13]2[CH2:17][C:16]3[CH:18]=[C:19](B4OC(C)(C)C(C)(C)O4)[CH:20]=[CH:21][C:15]=3[O:14]2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2].Br[C:32]1[CH:37]=[CH:36][C:35]([S:38]([CH3:41])(=[O:40])=[O:39])=[CH:34][N:33]=1>>[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([CH:13]2[CH2:17][C:16]3[CH:18]=[C:19]([C:32]4[CH:37]=[CH:36][C:35]([S:38]([CH3:41])(=[O:40])=[O:39])=[CH:34][N:33]=4)[CH:20]=[CH:21][C:15]=3[O:14]2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2] | CC(C)OC(=O)N1CCC(C2Cc3cc(B4OC(C)(C)C(C)(C)O4)ccc3O2)CC1 | CS(=O)(=O)c1ccc(Br)nc1 | null | null | null | null | null | null | null | 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 is prepared from 4-[5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-2,3-dihydro-benzofuran-2-yl]-piperidine-1-carboxylic acid isopropyl ester and 2-bromo-5-methanesulfonyl-pyridine following a procedure analogous to that described in Example 1. | CC(C)OC(=O)N1CCC(C2Cc3cc(-c4ccc(S(C)(=O)=O)cn4)ccc3O2)CC1 | null | 58 | null |
1,113,520 | ord_dataset-375a420ee9b042918ddca20f02df37d3 | null | 2011-01-01T00:11:00 | true | [CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:48][CH3:49])=[C:10]([CH2:19][NH:20][C:21]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([NH:31][CH2:32][C:33]4[CH:34]=[C:35]([C:40]5[CH:45]=[CH:44][CH:43]=[C:42]([CH2:46][OH:47])[CH:41]=5)[C:36]([F:39])=[CH:37][CH:38]=4)=[O:30])[CH:24]=3)=[O:22])[C:11]([NH:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2]>C1COCC1.O=[Mn]=O>[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:48][CH3:49])=[C:10]([CH2:19][NH:20][C:21]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([NH:31][CH2:32][C:33]4[CH:34]=[C:35]([C:40]5[CH:45]=[CH:44][CH:43]=[C:42]([CH:46]=[O:47])[CH:41]=5)[C:36]([F:39])=[CH:37][CH:38]=4)=[O:30])[CH:24]=3)=[O:22])[C:11]([NH:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2] | CCc1nc2c(cnn2CC)c(NC2CCOCC2)c1CNC(=O)c1cccc(C(=O)NCc2ccc(F)c(-c3cccc(CO)c3)c2)c1 | null | null | O=[Mn]=O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | 25 | 16 | To N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N′-{[6-fluoro-3′-(hydroxymethyl)-3-biphenylyl]methyl}-1,3-benzenedicarboxamide (0.665 g, 1 mmol) in THF (20 mL) was added MnO2 (0.869 g, 10.00 mmol) and the mixture was stirred at room temperature for 16 h. More MnO2 (10 eq) was added and stirred at room temperature for 4 h and then again for 22 h and then more MnO2 (10 eq) was added. This mixture was stirred at room temperature for 21 h and 94 h then filtered and concentrated to afford the title compound (0.6472 g, 98%). LC-MS m/z 663 (M+H)+. | CCc1nc2c(cnn2CC)c(NC2CCOCC2)c1CNC(=O)c1cccc(C(=O)NCc2ccc(F)c(-c3cccc(C=O)c3)c2)c1 | null | 97.7 | null |
117,853 | ord_dataset-3708161f4ba04e959b9a7a8d59fd86e1 | null | 1984-01-01T00:05:00 | true | [C:1]([NH:3][C:4](=[N:7][CH2:8][CH2:9][S:10][CH2:11][C:12]1[NH:16][CH:15]=[N:14][C:13]=1[CH3:17])SC)#[N:2].[CH2:18]([NH2:23])[CH2:19][CH2:20][C:21]#[CH:22]>C(#N)C>[C:1]([NH:3][C:4]([NH:7][CH2:8][CH2:9][S:10][CH2:11][C:12]1[NH:16][CH:15]=[N:14][C:13]=1[CH3:17])=[N:23][CH2:18][CH2:19][CH2:20][C:21]#[CH:22])#[N:2] | CSC(=NCCSCc1[nH]cnc1C)NC#N | C#CCCCN | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC#N | null | null | null | null | null | null | null | null | null | null | null | 96 | A mixture of N-cyano-N'-{2-[(4-methyl-5-imidazolyl)methylthio]ethyl}-S-methylisothiourea (3.00 g., 0.0111 mole) and 4-pentyn-1-amine (3.69 g., 0.0445 mole) in 60 ml. of acetonitrile was stirred at reflux for 24 hours, and then allowed to stand at room temperature for 96 hours. The solvent and excess amine were removed under reduced pressure and the residual yellow gum was purified by chromatography on 50 g. of 100-200 mesh silica gel, using gradient elution with methylene chloride/methanol (99:1-96:4). The middle fractions indicated by TLC to be pure were combined and evaporated to give 1.91 g. of yellow gum which was crystallized at -15° C. from 18 ml. of ethyl acetate. The resulting white solid (1.25 g.) was recrystallized at -15° C. from 10 ml. of acetonitrile to give 1.063 g. of product; m.p. 99°-103° C. | C#CCCCN=C(NC#N)NCCSCc1[nH]cnc1C | null | null | null |
1,401,261 | ord_dataset-7456bda2326f4bebaa874a5474d4cc0d | null | 2014-01-01T00:03:00 | true | C(OC([N:8]1[CH2:12][CH2:11][C@H:10]([O:13][NH2:14])[CH2:9]1)=O)(C)(C)C.[ClH:15]>CCOC(C)=O>[ClH:15].[ClH:15].[NH:8]1[CH2:12][CH2:11][C@H:10]([O:13][NH2:14])[CH2:9]1 | CC(C)(C)OC(=O)N1CC[C@H](ON)C1 | null | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOC(C)=O | null | null | null | null | null | null | null | null | null | null | null | null | (S)-1-tert-Butoxycarbonyl-3-pyrrolidinyloxyamine (1.67 g) was dissolved in a 5M HCl solution in EtOAc (20 ml). After 1 h the solvent was removed under reduced pressure to give (S)-3-pyrrolidinyloxyamine dihydrochloride (1.04 g, 73%) as an off-white solid. | NO[C@H]1CCNC1 | null | 73 | null |
332,062 | ord_dataset-1558660634294cc8ad7e01746e9083fd | null | 1996-01-01T00:06:00 | true | [CH2:1]([C:3]1[CH:4]=[C:5]([OH:20])[CH:6]=[CH:7][C:8]=1[O:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][CH:17]([CH3:19])[CH3:18])=[CH:12][CH:11]=1)[CH3:2].C(=O)([O-])[O-].[K+].[K+].[Br:27][C:28]([Br:32])=[CH:29][CH2:30]Br>CN(C)C=O>[CH2:1]([C:3]1[CH:4]=[C:5]([O:20][CH2:30][CH:29]=[C:28]([Br:32])[Br:27])[CH:6]=[CH:7][C:8]=1[O:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][CH:17]([CH3:19])[CH3:18])=[CH:12][CH:11]=1)[CH3:2] | BrCC=C(Br)Br | CCc1cc(O)ccc1Oc1ccc(OC(C)C)cc1 | null | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | 0 | null | To a mixture of 0.65 g of 3-ethyl-4-(4-isopropoxyphenoxy)phenol, 0.35 g of potassium carbonate and 10 ml of N,N-dimethylformamide, a solution prepared by dissolving 0.73 g of 1,1,3-tribromo-1-propene in 5 ml of N,N-dimethylformamide was added dropwise at room temperature with stirring. After stirring at room temperature for 12 hours, the reaction solution was poured into ice-water, and extracted twice with 50 ml, of diethyl ether. Then, the ether layers were combined, washed with water, dried over anhydrous magnesium sulfate and then concentrated to give a crude product. This crude product was subjected to silica gel chromatography to give 0.80 g of 3-ethyl-4-(4-isopropoxyphenoxy)-1-(3,3-dibromo-2-propenyloxy)benzene, yield 71%; nD23.0 1.5761. | CCc1cc(OCC=C(Br)Br)ccc1Oc1ccc(OC(C)C)cc1 | null | 71.3 | null |
425,210 | ord_dataset-1ecf96d88f254270bff816ee7eeffef6 | null | 1999-01-01T00:02:00 | true | N(C(OCC)=O)=NC(OCC)=O.O[C@H:14]1[CH2:18][N:17]([C:19]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][C:26]([N+:29]([O-:31])=[O:30])=[CH:25][CH:24]=2)=[O:20])[C@H:16]([C:32]([N:34]2[CH2:39][CH2:38][N:37]([CH2:40][CH2:41][O:42][C:43]([O:45][CH2:46][C:47]3[CH:52]=[CH:51][C:50]([N+:53]([O-:55])=[O:54])=[CH:49][CH:48]=3)=[O:44])[CH2:36][CH2:35]2)=[O:33])[CH2:15]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[SH:75]CC(O)=O>O1CCCC1>[SH:75][C@@H:14]1[CH2:18][N:17]([C:19]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][C:26]([N+:29]([O-:31])=[O:30])=[CH:25][CH:24]=2)=[O:20])[C@H:16]([C:32]([N:34]2[CH2:39][CH2:38][N:37]([CH2:40][CH2:41][O:42][C:43]([O:45][CH2:46][C:47]3[CH:52]=[CH:51][C:50]([N+:53]([O-:55])=[O:54])=[CH:49][CH:48]=3)=[O:44])[CH2:36][CH2:35]2)=[O:33])[CH2:15]1 | O=C(O)CS | O=C(OCCN1CCN(C(=O)[C@@H]2C[C@@H](O)CN2C(=O)OCc2ccc([N+](=O)[O-])cc2)CC1)OCc1ccc([N+](=O)[O-])cc1 | null | CCOC(=O)N=NC(=O)OCC | c1ccc(P(c2ccccc2)c2ccccc2)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | null | 0.17 | A solution of 36.5 g of diethyl azodicarboxylate in 100 ml of tetrahydrofuran was added dropwise, whilst ice-cooling, to a solution of 105 g of (2S,4R)-4-hydroxy-2-{4-[2-(4-nitrobenzyloxycarbonyl)oxyethyl]-1-piperazinylcarbonyl}-1-(4-nitrobenzyloxycarbonyl)pyrrolidine [prepared as described in steps 90(b)(i), 90(b)(i') and 90(b)(i") above] and 55 g of triphenylphosphine in 700 ml of tetrahydrofuran, and the resulting mixture was stirred at the same temperature for 10 minutes. A solution of 15.9 g of mercaptoacetic acid in 100 ml of tetrahydrofuran was then added dropwise to the mixture, and the mixture was stirred at room temperature for 1 hour. At the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure, and the concentrate was dissolved in 1.5 liters of ethyl acetate. The resulting solution was then washed with water and with an aqueous solution of sodium chloride, in that order, after which it was dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure, and then the residue was mixed with 400 ml of diisopropyl ether. The diisopropyl ether-soluble materials were extracted and discarded. The same extraction operations were repeated four times, and then the resulting residue was purified by column chromatography through 3 kg of silica gel, using a gradient elution method, with mixtures of ethyl acetate and methanol ranging from 1:0 to 20:1 by volume as the eluent, to give 88.4 g of the title compound, as a colorless powder. | O=C(OCCN1CCN(C(=O)[C@@H]2C[C@H](S)CN2C(=O)OCc2ccc([N+](=O)[O-])cc2)CC1)OCc1ccc([N+](=O)[O-])cc1 | null | 82.9 | null |
1,173,111 | ord_dataset-d24cc23b3db94284bb83a2ccdd9eb880 | null | 2012-01-01T00:05:00 | true | Br[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][CH:9]=2)[N:4]([S:11]([C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=2)(=[O:13])=[O:12])[CH:3]=1.[Cl:21][C:22]1[CH:27]=[C:26](B(O)O)[CH:25]=[CH:24][N:23]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.C(OCC)(=O)C.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>[Cl:21][C:22]1[CH:27]=[C:26]([C:2]2[C:10]3[C:5](=[N:6][CH:7]=[CH:8][CH:9]=3)[N:4]([S:11]([C:14]3[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=3)(=[O:13])=[O:12])[CH:3]=2)[CH:25]=[CH:24][N:23]=1 | Cc1ccc(S(=O)(=O)n2cc(Br)c3cccnc32)cc1 | OB(O)c1ccnc(Cl)c1 | 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 | CCOC(C)=O | null | null | null | null | null | null | null | null | null | null | null | A mixture of azaindole 3 (80 mg, 0.23 mmol), 2-chloropyridine-4-boronic acid (41 mg, 0.27 mmol), Pd(Ph3P)4 (20 mg, 0.11 mmol) and 2 M sodium carbonate (0.34 mL, 0.68 mmol) in 2 mL of DME was microwaved on high at 160° C. for under nitrogen for 15 minutes. Diluted with ethyl acetate and the organic phase washed with water and brine then dried (Na2SO4) and concentrated in vacuo. The residue was subjected to flash chromatography (40% EtOAc/60% hexanes) to give 60 mg (68%) of the desired product 14. 1H NMR CDCl3 8.6 (d, 2H), 8.1 (m, 4H), 7.25 (m, 5H), 2.5 (s, 3H). The 2-chloropyridine could be displaced, for example, with benzylamine in a microwave reaction at 250° C. for 30 min followed by deprotection to give compound 15. | Cc1ccc(S(=O)(=O)n2cc(-c3ccnc(Cl)c3)c3cccnc32)cc1 | null | 68 | null |
1,183,857 | ord_dataset-9cd817a75dfc4fe7ad19d4232772d5ff | null | 2012-01-01T00:07:00 | true | [NH2:1][C@:2]1([C:14]([O:16][CH3:17])=[O:15])[CH2:6][CH2:5][C@@H:4]([C:7]2[CH:12]=[CH:11][C:10]([Br:13])=[CH:9][CH:8]=2)[CH2:3]1.[CH2:18]([O:25][C:26](ON1C(=O)CCC1=O)=[O:27])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C.O>[CH2:18]([O:25][C:26]([NH:1][C@:2]1([C:14]([O:16][CH3:17])=[O:15])[CH2:6][CH2:5][C@@H:4]([C:7]2[CH:12]=[CH:11][C:10]([Br:13])=[CH:9][CH:8]=2)[CH2:3]1)=[O:27])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1 | COC(=O)[C@@]1(N)CC[C@@H](c2ccc(Br)cc2)C1 | O=C(OCc1ccccc1)ON1C(=O)CCC1=O | null | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CC#N | null | null | null | null | null | null | null | null | null | 25 | 1 | To (1R,3R)-methyl 1-amino-3-(4-bromophenyl)cyclopentanecarboxylate (1.5 g, 5.03 mmol) in acetonitrile (7.2 ml) and water (1.800 ml) was added N-(Benzyloxycarbonyloxy)succinimide (1.254 g, 5.03 mmol) followed by potassium carbonate (0.695 g, 5.03 mmol). The reaction mixture was stirred for 1 hour at room temperature. The solvent was removed and the remaining aqueous slurry was taken up in water and ethyl acetate. The organic layer was removed and washed with brine, dried over MgSO4 and concentrated in vacuo. The crude was purified by flash chromatography to yield (1R,3R)-methyl 1-(benzyloxycarbonylamino)-3-(4-bromophenyl)cyclopentanecarboxylate (1.4 g, 3.24 mmol, 64.4% yield) as an off white gum. | COC(=O)[C@@]1(NC(=O)OCc2ccccc2)CC[C@@H](c2ccc(Br)cc2)C1 | null | 64.4 | null |
195,473 | ord_dataset-b83b16f2fb1a4f8782f3d82c1766cc6b | null | 1989-01-01T00:08:00 | true | Cl[CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1/[CH:13]=[CH:14]/[C:15]1[S:16][C:17]2[CH:23]=[CH:22][CH:21]=[CH:20][C:18]=2[N:19]=1.[NH:24]1[CH:28]=[CH:27][N:26]=[CH:25]1.Cl>>[N:24]1([CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2/[CH:13]=[CH:14]/[C:15]2[S:16][C:17]3[CH:23]=[CH:22][CH:21]=[CH:20][C:18]=3[N:19]=2)[CH:28]=[CH:27][N:26]=[CH:25]1 | c1c[nH]cn1 | ClCCCCOc1ccccc1/C=C/c1nc2ccccc2s1 | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The named compound was prepared as described in Example 38 starting with (H) of Example 38 (3.0 g, 8.7 mmol) and using imidazole in place of dipropylamine to produce 1.5 g (46% yield) of the named compound as the HCl salt, mp 214°-217° C. IR(KBr): 3400, 1595 cm-1. MS: 376(MH+). 1H NMR (CD3OD): δ 9.01 (s, 1H), 7.88-6.91 (m, 12H), 4.21 (t, J=5.2 Hz, 2H), 3.34 (t, J=5.2 Hz, 2H), 2.25 (m, 4H). | C(=C/c1ccccc1OCCCCn1ccnc1)\c1nc2ccccc2s1 | null | 46 | null |
179,188 | ord_dataset-4d84abdf99524e0fb6c42ab2a3300790 | null | 1988-01-01T00:10:00 | true | [F:1][C:2]1[CH:3]=[C:4]([C:10]([F:13])([F:12])[F:11])[CH:5]=[CH:6][C:7]=1[O:8]C.S(=O)(=O)(O)O.[N+:19]([O-])([O-:21])=[O:20].[K+]>ClCCCl>[F:1][C:2]1[CH:3]=[C:4]([C:10]([F:13])([F:12])[F:11])[CH:5]=[C:6]([N+:19]([O-:21])=[O:20])[C:7]=1[OH:8] | O=[N+]([O-])[O-] | COc1ccc(C(F)(F)F)cc1F | null | O=S(=O)(O)O | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCCl | null | null | null | null | null | null | null | null | null | null | 0 | null | The product from (c) (4.1 g) in 1,2-dichloro-ethane (25 ml) was chilled to -10° C. and concentrated sulphuric acid (25 ml) added. The mixture was stirred and kept at -5° to -10° C. while potassium nitrate (2.3 g) was added in portions over a period of 30 minutes. The mixture was stirred for a further 30 minutes at below 0° C. and then poured on to ice (150 ml). The mixture was extracted with chloroform (150 ml) and the extracts washed with water (100 ml), dried (MgSO4) and evaporated to give 3-fluoro-4-hydroxy-5-nitrobenzotrifluoride as a pale yellow liquid (4.1 g). | O=[N+]([O-])c1cc(C(F)(F)F)cc(F)c1O | null | 86.2 | null |
453,439 | ord_dataset-3bcdb559226a40d89406474c02d082d1 | null | 1999-01-01T00:12:00 | true | [Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[O:13][N:12]=[C:11]([OH:14])[CH:10]=2)[CH:5]=[CH:6][C:7]=1[Cl:8].[C:15]([O:19][C:20]([NH:22][CH2:23][CH2:24]O)=[O:21])([CH3:18])([CH3:17])[CH3:16]>>[C:15]([O:19][C:20]([NH:22][CH2:23][CH2:24][O:14][C:11]1[CH:10]=[C:9]([C:4]2[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=2)[O:13][N:12]=1)=[O:21])([CH3:18])([CH3:17])[CH3:16] | CC(C)(C)OC(=O)NCCO | Oc1cc(-c2ccc(Cl)c(Cl)c2)on1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | 5-(3,4-Dichlorophenyl)-3-hydroxyisoxazole (0.3 g) and 2-(N-tert-butoxycarbonylamino)ethanol (0.23 g) were subjected to reaction and post-treatment in a similar manner to that described in Example 9(a) to obtain the title compound (0.41 g, 85%) as a colorless powder. | CC(C)(C)OC(=O)NCCOc1cc(-c2ccc(Cl)c(Cl)c2)on1 | null | 84.2 | null |
790,138 | ord_dataset-530502f8e61e455784f93c5faa45c94b | null | 2007-01-01T00:09:00 | true | [C:1]([N:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1)(=[O:3])[CH3:2].Br[CH2:11][CH2:12][OH:13].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[C:1]([N:4]1[CH2:9][CH2:8][N:7]([CH2:11][CH2:12][OH:13])[CH2:6][CH2:5]1)(=[O:3])[CH3:2] | CC(=O)N1CCNCC1 | 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 | null | null | A mixture of 1-acetylpiperazine (2.5 g, 19.5 mmol), 2-bromoethanol (1.38 ml, 19.5 mmol) and potassium carbonate (6.7 g, 48.8 mmol) in acetonitrile (30 ml) was heated at reflux for 3 hours. The mixture was cooled, filtered and concentrated under reduced pressure. The residue was purified by column chromatography eluting with methylene chloride/methanol (9/1) to give 2-(4-acetylpiperazin-1-yl)ethanol (1.89 g, 56%) as a colourless oil. | CC(=O)N1CCN(CCO)CC1 | null | 56.3 | null |
1,581,517 | ord_dataset-380e279f82154dba9e08ab51b3bdd08a | null | 2015-01-01T00:05:00 | true | [NH2:1][C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:12][OH:13]>C(Cl)Cl.[O-2].[O-2].[Mn+4]>[NH2:1][C:2]1[C:7]([C:8]([F:9])([F:10])[F:11])=[CH:6][CH:5]=[CH:4][C:3]=1[CH:12]=[O:13] | Nc1c(CO)cccc1C(F)(F)F | null | null | [Mn+4] | [O-2] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | 25 | 18 | Manganese dioxide (27 g, 0.32 mol) was added to a solution of [2-amino-3-(trifluoromethyl)phenyl]methanol (12.0 g, 0.063 mol) in DCM (150 mL) and the mixture was stirred for 18 h at room temperature. After this time, more manganese dioxide (27 g, 0.32 mol) was added, and the reaction mixture was left for a further 18 h. The reaction mixture was filtered through Celite, then the solvent was removed in vacuo to afford the title compound (9.5 g, 80%) as an orange oil. δH (DMSO-d6) 9.93 (s, 1H), 7.68 (m, 2H), 6.82 (m, 3H). | Nc1c(C=O)cccc1C(F)(F)F | null | 79.7 | null |
474,579 | ord_dataset-d56f0a7ec215495c92e641d9fa932d28 | null | 2000-01-01T00:09:00 | true | [SH:1][C:2]1[NH:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.[CH2:11]([N:15]=[C:16]=[O:17])[CH2:12][CH2:13][CH3:14]>>[CH2:11]([NH:15][C:16]([N:3]1[C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[NH:6][C:2]1=[S:1])=[O:17])[CH2:12][CH2:13][CH3:14] | CCCCN=C=O | Sc1nc2ccccc2[nH]1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | 135 | null | The mixture of 2-mercaptobenzimidazole (29.30 g, 0.195 mole) and butyl isocyanate (48.3 mL, 0.33 mole) in a 500 ml of round-bottom flask equipped with a condenser was heated to 130-140° C. in an oil bath for 45 min. After the reaction mixture was cooled to room temperature, the solid was filtered, washed with hexane, and dried under vacuum to give 43.48 g (89%) of 1-(butylcarbamoyl)-1,3-dihydrobenz-imidazole-2-thione as white crystals: mp 179-180° C. | CCCCNC(=O)n1c(=S)[nH]c2ccccc21 | null | 89.4 | null |
1,023,845 | ord_dataset-136cfada6ce247b4919085a57363459e | null | 2011-01-01T00:01:00 | true | [C:1]([Si:5]([CH3:38])([CH3:37])[O:6][C:7]1[CH:8]=[C:9]([C:13]2[N:14]=[C:15]([N:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)[C:16]3[S:21][C:20]([CH2:22][N:23]4[CH2:28][C@H:27]([CH3:29])[NH:26][C@H:25]([CH3:30])[CH2:24]4)=[CH:19][C:17]=3[N:18]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[C:46](Cl)(=[O:48])[CH3:47]>ClCCl>[C:1]([Si:5]([CH3:38])([CH3:37])[O:6][C:7]1[CH:8]=[C:9]([C:13]2[N:14]=[C:15]([N:31]3[CH2:32][CH2:33][O:34][CH2:35][CH2:36]3)[C:16]3[S:21][C:20]([CH2:22][N:23]4[CH2:24][C@H:25]([CH3:30])[N:26]([C:46](=[O:48])[CH3:47])[C@H:27]([CH3:29])[CH2:28]4)=[CH:19][C:17]=3[N:18]=2)[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:2])[CH3:3] | CC(=O)Cl | C[C@@H]1CN(Cc2cc3nc(-c4cccc(O[Si](C)(C)C(C)(C)C)c4)nc(N4CCOCC4)c3s2)C[C@H](C)N1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | CCN(CC)CC | null | null | null | null | null | null | null | null | null | null | 8 | To a solution of 2-[3-(tert-butyl-dimethyl-silanyloxy)-phenyl]-6-((3R,5S)-3,5-dimethyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (80 mg, 0.14 mmol) in dichloromethane (5 mL) was added triethylamine (40 μL, 2.0 equivalents) followed by acetyl chloride (15 μL, 1.5 eq.). After stirring overnight, the reaction mixture was diluted with dichloromethane, washed with aqueous sodium carbonate solution, dried (MgSO4) and the solvent removed in vacuo to yield 1-((2R,6S)-4-{2-[3-(tert-butyl-dimethyl-silanyloxy)-phenyl]-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl}-2,6-dimethyl-piperazin-1-yl)-ethanone (80 mg) as a white solid. Removal of the tert-butyldimethylsilyl protecting group was performed as described above to yield the title compound. | CC(=O)N1[C@H](C)CN(Cc2cc3nc(-c4cccc(O[Si](C)(C)C(C)(C)C)c4)nc(N4CCOCC4)c3s2)C[C@@H]1C | null | null | null |
909,492 | ord_dataset-46d216f2c4374ef5b9df90427e2a4cd4 | null | 2009-01-01T00:09:00 | true | N[C:2]1[C:6]([C:7]#[N:8])=[C:5]([S:9][CH3:10])[S:4][C:3]=1[C:11]([O:13][CH2:14][CH3:15])=[O:12].N(OCCC(C)C)=O>CN(C)C=O>[C:7]([C:6]1[CH:2]=[C:3]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[S:4][C:5]=1[S:9][CH3:10])#[N:8] | CCOC(=O)c1sc(SC)c(C#N)c1N | null | null | CC(C)CCON=O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | 25 | null | A solution of 50 g (0.21 mol) of ethyl 3-amino-4-cyano-5-methylsulfanylthiophene-2-carboxylate in 500 mL of dimethylformamide under an argon atmosphere is heated to a temperature in the region of 60° C., and a solution of 71.1 mL (0.45 mol) of isopentyl nitrite in 100 mL of dimethylformamide is then introduced with stirring, while maintaining the temperature between 65 and 70° C. The reaction mixture is then stirred at a temperature in the region of 60° C. for 2.5 hours, and then cooled to a temperature in the region of 25° C. and stirred for one hour. The mixture is then treated with 1 L of ice-cold water and then stirred at a temperature in the region of 0° C. for one hour. The precipitate obtained is filtered off and then washed successively three times with 200 mL of water and three times with 200 mL of petroleum ether. 40.5 g (86%) of ethyl 4-cyano-5-methylsulfanylthiophene-2-carboxylate are thus obtained, after drying under reduced pressure, in the form of a yellow crystalline powder melting at 100° C. MS-CI (NH3): 245(+)=(M+NH4)(+). | CCOC(=O)c1cc(C#N)c(SC)s1 | null | 84.8 | null |
275,326 | ord_dataset-02ee2261663048188cf6d85d2cc96e3f | null | 1993-01-01T00:09:00 | true | [CH2:1]([OH:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:9][OH:10]>>[C:1]1([C:2]2[C:7](=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:9][O:10]1)=[O:8] | CO | OCc1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The procedure described in method F is repeated, except that the methanol is replaced by 50 ml of benzyl alcohol, affording a phthalide compound of the formula ##STR19## melting point 183°-184° C. | O=C1OCc2ccccc21 | null | null | null |
1,519,142 | ord_dataset-8c74302143c04eb9983e4b3a7ead2d72 | null | 2014-01-01T00:12:00 | true | [CH3:1][C:2]1([CH3:22])[CH2:11][CH2:10][C:9]([CH3:13])([CH3:12])[C:8]2[CH:7]=[C:6]([C:14]3[N:15]=[C:16]([CH2:19][CH2:20][NH2:21])[S:17][CH:18]=3)[CH:5]=[CH:4][C:3]1=2.[C:23]([O:27][C:28]([NH:30][C@@H:31]([CH2:35][OH:36])[C:32](O)=[O:33])=[O:29])([CH3:26])([CH3:25])[CH3:24]>>[C:23]([O:27][C:28](=[O:29])[NH:30][C@H:31]([C:32](=[O:33])[NH:21][CH2:20][CH2:19][C:16]1[S:17][CH:18]=[C:14]([C:6]2[CH:5]=[CH:4][C:3]3[C:2]([CH3:22])([CH3:1])[CH2:11][CH2:10][C:9]([CH3:12])([CH3:13])[C:8]=3[CH:7]=2)[N:15]=1)[CH2:35][OH:36])([CH3:26])([CH3:24])[CH3:25] | CC(C)(C)OC(=O)N[C@@H](CO)C(=O)O | CC1(C)CCC(C)(C)c2cc(-c3csc(CCN)n3)ccc21 | null | null | null | null | null | null | null | 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 preparation is carried out as already described starting from 186 mg (0.59 mmol) of 2-[4-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)thiazol-2-yl]ethylamine from step b and 133 mg (0.65 mmol) of (S)-2-tert-butoxycarbonylamino-3-hydroxypropionic acid. | CC(C)(C)OC(=O)N[C@@H](CO)C(=O)NCCc1nc(-c2ccc3c(c2)C(C)(C)CCC3(C)C)cs1 | null | null | null |
836,807 | ord_dataset-074f86301ec5441ab3b52d902ac06949 | null | 2008-01-01T00:09:00 | true | [Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:16])=[C:6]([C:8]2[CH:13]=[C:12](Cl)[N:11]=[C:10]([NH2:15])[N:9]=2)[CH:7]=1.[NH2:17][C:18]1[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[CH:20][CH:19]=1>>[NH2:15][C:10]1[N:11]=[C:12]([NH:17][C:18]2[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[CH:20][CH:19]=2)[CH:13]=[C:8]([C:6]2[CH:7]=[C:2]([Br:1])[CH:3]=[CH:4][C:5]=2[CH3:16])[N:9]=1 | Cc1ccc(Br)cc1-c1cc(Cl)nc(N)n1 | N#Cc1ccc(N)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 | Following the method described in Example 26, 4-(5-bromo-2-methyl-phenyl)-6-chloro-pyrimidin-2-ylamine and 4-amino-benzonitrile provided the title compound (72% yield). 1H NMR (CD3OD) δ 2.40 (s, 3H, CH3), 6.38 (s, 1H, Ar), 7.39 (d, 1H, J=8.9 Hz, Ar), 7.68-7.69 (m, 2H, Ar), 7.78-7.80 (m, 2H, Ar), 8.07 (d, 2H, J=7.6 Hz, Ar). | Cc1ccc(Br)cc1-c1cc(Nc2ccc(C#N)cc2)nc(N)n1 | null | 72 | null |
1,558,184 | ord_dataset-4e54080057a44c3887653391e24c90b6 | null | 2015-01-01T00:03:00 | true | [H-].[Na+].[Br:3][C:4]1[CH:5]=[C:6]([CH2:21][OH:22])[CH:7]=[N:8][C:9]=1[O:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=1.Cl[C:24]1[CH:25]=[C:26]2[N:33]([CH3:34])[CH2:32][CH2:31][N:27]2[C:28](=[O:30])[N:29]=1>C1COCC1>[Br:3][C:4]1[CH:5]=[C:6]([CH2:21][O:22][C:24]2[CH:25]=[C:26]3[N:33]([CH3:34])[CH2:32][CH2:31][N:27]3[C:28](=[O:30])[N:29]=2)[CH:7]=[N:8][C:9]=1[O:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:18])([F:19])[F:20])[CH:12]=1 | OCc1cnc(Oc2cccc(C(F)(F)F)c2)c(Br)c1 | CN1CCn2c1cc(Cl)nc2=O | 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 | Prepared in a manner similar to that described for E1 using NaH (6.89 mg, 0.172 mmol), (5-bromo-6-(3-(trifluoromethyl)phenoxy)pyridin-3-yl)methanol (60 mg, 0.17 mmol) in THF (8 mL) and 7-chloro-1-methyl-2,3-dihydroimidazo[1,2-c]pyrimidin-5(1H)-one (32.0 mg, 0.172 mmol). | CN1CCn2c1cc(OCc1cnc(Oc3cccc(C(F)(F)F)c3)c(Br)c1)nc2=O | null | null | null |
1,231,064 | ord_dataset-e96f5a2842f14e5380461c234100f05a | null | 2012-01-01T00:12:00 | true | [C:1]([O:5][C:6](=[O:31])[CH2:7][O:8][C@H:9]1[CH2:14][CH2:13][CH2:12][C@@H:11]([O:15][C:16]2[C:17]3[C:24]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)=[CH:23][O:22][C:18]=3[N:19]=[CH:20][N:21]=2)[CH2:10]1)([CH3:4])([CH3:3])[CH3:2].C1C(=O)N([Br:39])C(=O)C1>ClC(Cl)(Cl)Cl>[C:1]([O:5][C:6](=[O:31])[CH2:7][O:8][C@H:9]1[CH2:14][CH2:13][CH2:12][C@@H:11]([O:15][C:16]2[C:17]3[C:24]([C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=4)=[C:23]([Br:39])[O:22][C:18]=3[N:19]=[CH:20][N:21]=2)[CH2:10]1)([CH3:4])([CH3:2])[CH3:3] | O=C1CCC(=O)N1Br | CC(C)(C)OC(=O)CO[C@H]1CCC[C@@H](Oc2ncnc3occ(-c4ccccc4)c23)C1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClC(Cl)(Cl)Cl | null | null | null | null | null | null | null | null | null | null | 60 | 2 | Suspend 100 mg (0.236 mmol) of (+/−)-cis-({3-[(5-phenylfuro[2,3-d]pyrimidin-4-yl)oxy]cyclohexyl}oxy)acetic acid tert-butyl ester in 0.2 ml of tetrachloromethane and add 46.1 mg (0.259 mmol) of NBS. Stir the reaction mixture at 60° C. for a total of 2 h, and add a further 23 mg of NBS after 1 h. After cooling, remove the tetrachloromethane under reduced pressure and purify the residue by preparative RP-HPLC (eluent: acetonitrile/water). 43.6 mg (36.8% of theory) of the target product are obtained. | CC(C)(C)OC(=O)CO[C@H]1CCC[C@@H](Oc2ncnc3oc(Br)c(-c4ccccc4)c23)C1 | null | null | null |
1,336,078 | ord_dataset-08852243bba44cb28769a5833f1515fe | null | 2013-01-01T00:09:00 | true | [CH2:1]([O:3][C:4]([C:6]1[CH:14]=[C:13]2[C:9]([C:10]([CH:25]=[O:26])=[C:11]([CH:22]([CH3:24])[CH3:23])[N:12]2[CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=2)=[CH:8][CH:7]=1)=[O:5])[CH3:2].[O-:27]Cl=O.[Na+]>CC(O)(C)C.CC(=CC)C.O>[CH2:1]([O:3][C:4]([C:6]1[CH:14]=[C:13]2[C:9]([C:10]([C:25]([OH:27])=[O:26])=[C:11]([CH:22]([CH3:23])[CH3:24])[N:12]2[CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=2)=[CH:8][CH:7]=1)=[O:5])[CH3:2] | [O-][Cl+][O-] | CCOC(=O)c1ccc2c(C=O)c(C(C)C)n(Cc3ccccn3)c2c1 | null | CC=C(C)C | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CC(C)(C)O | null | null | null | null | null | null | null | null | null | 25 | 12 | Following General Procedure D, ethyl3-formyl-2-isopropyl-1-(pyridin-2-ylmethyl)-1H-indole-6-carboxylate (Compound 36, 287 mg, 0.82 mmol) in t-BuOH (6 ml), 2-methyl-2-butene (2.29 ml) was added a solution of NaH2PO4 (1.97 g, 16.4mmol) and NaClO2 (80%, 1.48 g, 16.4 mmol) in H2O (6 ml). The mixture was stirred at room temperature for 12 h. The reaction mixture was extracted with EtOAc (×3) and the combined organic layer was washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by chromatography on silica gel (0→50% EtOAc-hexanes) to yield the title compound as a light yellow solid. | CCOC(=O)c1ccc2c(C(=O)O)c(C(C)C)n(Cc3ccccn3)c2c1 | null | null | null |
992,143 | ord_dataset-b6d8835b0c934476a36e6149e7597487 | null | 2010-01-01T00:09:00 | true | [SH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:5]#[N:6].C(=O)([O-])[O-].[K+].[K+].Br[CH2:23][CH2:24][CH2:25][O:26][Si:27]([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28]>CN(C)C=O>[Si:27]([O:26][CH2:25][CH2:24][CH2:23][S:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)[C:5]#[N:6])([C:30]([CH3:31])([CH3:32])[CH3:33])([CH3:29])[CH3:28] | CC(C)(C)[Si](C)(C)OCCCBr | N#Cc1ccc(-c2ccccc2)c(S)c1 | null | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | 25 | 16 | To a solution of 3-mercapto-4-phenylbenzonitrile (0.44 g) in N,N-dimethylformamide (5.0 mL) was added potassium carbonate (0.43 g). Then (3-bromopropoxy)-tert-butyldimethylsilane (0.72 mL) was added, and the resulting mixture was stirred at room temperature for 16 hours. The reaction mixture was partitioned between diethyl ether (55 mL) and water (10 mL). The organic layer was washed with water (10 mL×2) and brine (10 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: hexane/ethylacetate=3/2) to give the title compound (0.8 g). | CC(C)(C)[Si](C)(C)OCCCSc1cc(C#N)ccc1-c1ccccc1 | null | null | null |
1,337,046 | ord_dataset-08852243bba44cb28769a5833f1515fe | null | 2013-01-01T00:09:00 | true | Br[CH2:2][CH2:3][N:4]1[C:28](=[O:29])[N:7]2[CH:8]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([OH:27])[CH:22]=3)[C:9]3[NH:10][C:11]4[C:16]([C:17]=3[CH2:18][C:6]2([CH3:30])[C:5]1=[O:31])=[CH:15][C:14]([O:19][CH3:20])=[CH:13][CH:12]=4.[CH2:32]([NH2:34])[CH3:33]>CO>[CH2:32]([NH:34][CH2:2][CH2:3][N:4]1[C:28](=[O:29])[N:7]2[CH:8]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([OH:27])[CH:22]=3)[C:9]3[NH:10][C:11]4[C:16]([C:17]=3[CH2:18][C:6]2([CH3:30])[C:5]1=[O:31])=[CH:15][C:14]([O:19][CH3:20])=[CH:13][CH:12]=4)[CH3:33] | CCN | COc1ccc2[nH]c3c(c2c1)CC1(C)C(=O)N(CCBr)C(=O)N1C3c1cccc(O)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | null | null | The title compound is prepared similarly as described for example 30 using (3aSR,10RS)-2-(2-Bromoethyl)-10-(3-hydroxy-phenyl)-6-methoxy-3a-methyl-3a,4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta[b]-fluorene-1,3-dione (example 24) and a 2 M solution of ethyl amine in methanol as starting materials. | CCNCCN1C(=O)N2C(c3cccc(O)c3)c3[nH]c4ccc(OC)cc4c3CC2(C)C1=O | null | null | null |
98,560 | ord_dataset-b37811c5ed724c3b844cc4d2b5640398 | null | 1982-01-01T00:09:00 | true | [CH2:1]([NH:17][C:18]1[CH:30]=[CH:29][C:21]([CH2:22][CH2:23][C:24](OCC)=[O:25])=[CH:20][CH:19]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].[H-].[Al+3].[Li+].[H-].[H-].[H-]>>[CH2:1]([NH:17][C:18]1[CH:30]=[CH:29][C:21]([CH2:22][CH2:23][CH2:24][OH:25])=[CH:20][CH:19]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16] | CCCCCCCCCCCCCCCCNc1ccc(CCC(=O)OCC)cc1 | null | null | [Al+3] | [H-] | [Li+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | By a method analogous to that described in Example 16, ethyl 4-hexadecylaminohydrocinnamate is reduced with lithium aluminum hydride to provide the title compound. | CCCCCCCCCCCCCCCCNc1ccc(CCCO)cc1 | null | null | null |
1,610,583 | ord_dataset-9cecb3a8d3b9494191b28dcefea66af2 | null | 2015-01-01T00:07:00 | true | [F:1]C1C=C2C(=CC=1)NC=C2C=O.C(O[C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[N:22]([C:26]([NH2:28])=[O:27])[CH:21]=[C:20]2[N:29]=[C:30]=[O:31])C=C>>[F:1][C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[N:22]([C:26]([NH2:28])=[O:27])[CH:21]=[C:20]2[N:29]=[C:30]=[O:31] | O=Cc1c[nH]c2ccc(F)cc12 | C=CCOc1ccc2c(c1)c(N=C=O)cn2C(N)=O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | was prepared from 5-fluoro-1H-indole-3-carbaldehyde using the protocol described for steps C, D and E in scheme A4 for the preparation of 5-allyloxy-3-isocyanato-indole-1-carboxylic acid amide. | NC(=O)n1cc(N=C=O)c2cc(F)ccc21 | null | null | null |
995,685 | ord_dataset-b6d8835b0c934476a36e6149e7597487 | null | 2010-01-01T00:09:00 | true | [CH3:1][N:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[N:4]=[C:3]1[CH2:11][C:12]1[CH:21]=[CH:20][C:15]([C:16]([O:18]C)=[O:17])=[CH:14][CH:13]=1.[OH-].[Na+]>CO>[CH3:1][N:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[N:4]=[C:3]1[CH2:11][C:12]1[CH:21]=[CH:20][C:15]([C:16]([OH:18])=[O:17])=[CH:14][CH:13]=1 | COC(=O)c1ccc(Cc2nc3ccccc3n2C)cc1 | null | null | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | 25 | null | A solution of methyl 4-[(1-methyl-1H-benzimidazol-2-yl)methyl]benzoate (7.0 g, 25 mmol) in methanol was treated with 2.5 N sodium hydroxide, heated at reflux temperature for 2 h, cooled to room temperature and concentrated in vacuo. The residue was dissolved in water and acidified with 6N HCl solution and filtered. The filtercake was air dried to afford 4-[(1-methyl-1H-benzoimidazol-2-yl)methyl]benzoic acid in 81% yield; 1H NMR (400 MHz, DMSO-d6): 7.90 (d, J=8 Hz, 2H), 7.57 (d, J=8 Hz, 1H), 7.49 (d, J=8 Hz, 1H), 7.40 (d, J=8 Hz, 2H), 7.17-7.20 (m, 2H), 4.39 (s, 2H), 3.70 (s, 3H). LCMS (ESI+) 276 (MH+). | Cn1c(Cc2ccc(C(=O)O)cc2)nc2ccccc21 | null | 81 | null |
605,595 | ord_dataset-273fda773e864aaf9b71a30a2d9f2162 | null | 2003-01-01T00:08:00 | true | [Cl:1][C:2]1[CH:13]=[CH:12][C:5](/[CH:6]=[CH:7]/[C:8]([O:10][CH3:11])=[O:9])=[C:4]([NH:14]S(C2C=CC=CC=2)(=O)=O)[CH:3]=1.[CH:24]1([C:28]([CH2:30]Br)=[O:29])[CH2:27][CH2:26][CH2:25]1>>[CH3:11][O:10][C:8](=[O:9])[CH2:7][C:6]1[C:5]2[C:4](=[CH:3][C:2]([Cl:1])=[CH:13][CH:12]=2)[NH:14][C:30]=1[C:28]([CH:24]1[CH2:27][CH2:26][CH2:25]1)=[O:29] | COC(=O)/C=C/c1ccc(Cl)cc1NS(=O)(=O)c1ccccc1 | O=C(CBr)C1CCC1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The title compound was prepared according to the procedure described in Example 57 from methyl trans-4-chloro-2-(phenylsulfonylamino)cinnamate (step 1 of Example 8, Method A) and bromomethyl cyclobutyl ketone*. | COC(=O)Cc1c(C(=O)C2CCC2)[nH]c2cc(Cl)ccc12 | null | null | null |
1,710,904 | ord_dataset-3f2a531ffbae4b9eb1048afcd7953beb | null | 2016-01-01T00:04:00 | true | [C:1]([N:8]1[CH2:16][CH2:15][CH2:14][C@H:10]([C:11]([OH:13])=O)[CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[CH3:17][NH:18][CH2:19][CH2:20][O:21][CH2:22][CH2:23][O:24][CH2:25][CH2:26][O:27][CH2:28][CH2:29][O:30][CH2:31][CH2:32][O:33][CH2:34][CH2:35][O:36][CH2:37][CH2:38][O:39][CH3:40].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH3:40][O:39][CH2:38][CH2:37][O:36][CH2:35][CH2:34][O:33][CH2:32][CH2:31][O:30][CH2:29][CH2:28][O:27][CH2:26][CH2:25][O:24][CH2:23][CH2:22][O:21][CH2:20][CH2:19][N:18]([CH3:17])[C:11]([C@H:10]1[CH2:14][CH2:15][CH2:16][N:8]([C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2])[CH2:9]1)=[O:13] | CC(C)(C)OC(=O)N1CCC[C@H](C(=O)O)C1 | CNCCOCCOCCOCCOCCOCCOCCOC | null | CN(C)C(On1nnc2cccnc21)=[N+](C)C | F[P-](F)(F)(F)(F)F | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | CCN(C(C)C)C(C)C | null | null | null | null | null | null | null | null | null | null | 1 | To a solution of Boc-(S)-nipecotic acid (137 mg, 0.60 mmol), N-methyl-2,5,8,11,14,17,20-heptaoxadocosan-22-amine 135c.1 (310 mg, 0.88 mmol) and DIPEA (335 mg, 2.6 mmol) in DMF (3 mL) was added HATU (285 mg, 0.75 mmol). The reaction was stirred for 1 hour and then the DMF was removed under vacuum. The residue was added to saturated aqueous NaHCO3 (10 mL) and extracted with DCM (3×20 mL). The combined organic layers were dried (Na2SO4) and concentrated to give (S)-tert-butyl 3-(2,5,8,11,14,17,20-heptaoxadocosan-22-yl(methyl)carbamoyl)piperidine-1-carboxylate (720 mg). | COCCOCCOCCOCCOCCOCCOCCN(C)C(=O)[C@H]1CCCN(C(=O)OC(C)(C)C)C1 | null | 212.5 | null |
133,767 | ord_dataset-34cf5f1378de4e34844aea93a2f9a9d3 | null | 1985-01-01T00:08:00 | true | [Na].[O-]CC.[Na+].[S:6]1[CH:10]=[CH:9][CH:8]=[C:7]1[CH:11]([OH:16])[C:12]([O:14]C)=O.[F:17][C:18]([F:29])([F:28])[C:19]1[CH:20]=[C:21]([CH2:25][C:26]#[N:27])[CH:22]=[CH:23][CH:24]=1>C(O)C.O>[S:6]1[CH:10]=[CH:9][CH:8]=[C:7]1[CH:11]1[C:12](=[O:14])[C:25]([C:21]2[CH:22]=[CH:23][CH:24]=[C:19]([C:18]([F:28])([F:17])[F:29])[CH:20]=2)=[C:26]([NH2:27])[O:16]1 | COC(=O)C(O)c1cccs1 | N#CCc1cccc(C(F)(F)F)c1 | null | CC[O-] | [Na+] | [Na] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CCO | null | null | null | null | null | null | null | null | null | null | null | A dry, 250-ml, three-neck, round-bottom flask equipped with a mechanical stirrer, addition funnel and a reflux condenser bearing a nitrogen inlet tube was charged with 4.2 g of sodium and 100 ml of absolute ethanol. To the resulting sodium ethoxide solution was added dropwise a mixture of 21.1 g of methyl thien-2-yl-hydroxyacetate and 22.7 g of m-trifluoromethylphenyl-acetonitrile in 20 ml of ethanol. The resulting mixture was heated at reflux for 4-5 hours after which time it was added to 300-400 ml of water and extracted with petroleum ether. The aqueous phase was acidified with aqueous 10 weight percent hydrochloric acid and extracted two times with diethyl ether. The ether extracts were washed twice with saturated aqueous sodium bicarbonate, dried over magnesium sulfate and concentrated in vacuo to yield a thick dark oil. This oil was triturated with 20-30% ether/petroleum ether which afforded 4.9 g of the title compound as a tan powder. | NC1=C(c2cccc(C(F)(F)F)c2)C(=O)C(c2cccs2)O1 | null | 12.3 | null |
1,205,264 | ord_dataset-fb72428f30234761b4216139dc228d0c | null | 2012-01-01T00:09:00 | true | O1[C:5]2([CH2:10][CH2:9][C:8]([C:11]3[C:12]([O:17][CH3:18])=[N:13][CH:14]=[CH:15][CH:16]=3)=[CH:7][CH2:6]2)[O:4]CC1.Cl>C(#N)C>[CH3:18][O:17][C:12]1[C:11]([C:8]2[CH2:9][CH2:10][C:5](=[O:4])[CH2:6][CH:7]=2)=[CH:16][CH:15]=[CH:14][N:13]=1 | COc1ncccc1C1=CCC2(CC1)OCCO2 | null | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC#N | null | null | null | null | null | null | null | null | null | null | 25 | null | To a mixture of 3-(1,4-Dioxa-spiro[4.5]dec-7-en-8-yl)-2-methoxy-pyridine (as prepared in the previous step, 211 mg, 0.854 mmol) in acetonitrile was added aqueous HCl (5 mL, 5 mmol, 1M). The mixture was stirred at room temperature until HPLC indicated consumption of starting material. The reaction mixture was poured onto saturated sodium bicarbonate solution and extracted with ethyl acetate. The organic layer washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography (SiO2, 0-10% MeOH/CH2Cl2) to afford 4-(2-methoxy-pyridin-3-yl)-cyclohex-3-enone. | COc1ncccc1C1=CCC(=O)CC1 | null | null | null |
1,174,393 | ord_dataset-0f9d2dbe929a45c3892ae75e81e99443 | null | 2012-01-01T00:06:00 | true | [C:1]([O:9][CH2:10][C@@:11]1([C:26]#[CH:27])[O:15][C@@H:14]([N:16]2[CH:24]=[C:22]([CH3:23])[C:20](=[O:21])[NH:19][C:17]2=[O:18])[CH2:13][C@H:12]1[OH:25])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(CC)CC.[Si]([O:39][S:40]([C:43](F)(F)F)(=O)=[O:41])(C)(C)C.O=O>CC([O-])=O.CC([O-])=O.[Pd+2]>[C:1]([O:9][CH2:10][C@@:11]1([C:26]#[CH:27])[O:15][C@@H:14]([N:16]2[CH:24]=[C:22]([CH3:23])[C:20](=[O:21])[NH:19][C:17]2=[O:18])[CH2:13][C@H:12]1[O:25][S:40]([CH3:43])(=[O:41])=[O:39])(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1 | C[Si](C)(C)OS(=O)(=O)C(F)(F)F | C#C[C@]1(COC(=O)c2ccccc2)O[C@@H](n2cc(C)c(=O)[nH]c2=O)C[C@H]1O | null | [Pd+2] | CC(=O)[O-] | O=O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(CC)CC | null | null | null | null | null | null | null | null | null | null | null | 0.5 | To a stirring mixture of 4 (3.58 g, 8.72 mmol) and Et3N (6.1 ml, 43.6 mmol) was added Me3SiOSO2CF3 (2.56 mL, 13.0 mmol) at 0° C. under positive pressure of dry Ar. The mixture was stirred for 30 min at the same temperature, and then partitioned between CH2Cl2 and sat. aqueous NaHCO3. The organic layer was dried (Na2SO4) and evaporated. The residue was dissolved in DMSO (12 mL). To this solution was added Pd(OAc)2 (98 mg, 0.44 mmol), and the mixture was stirred for 36 h under positive pressure of O2. The mixture was partitioned between EtOAc and brine. The organic layer was dried (Na2SO4), evaporated, and chromatographed on a silica gel column (hexane/EtOAc=5/1) to give 5 (3.13 g, 88%) as a white solid. | C#C[C@]1(COC(=O)c2ccccc2)O[C@@H](n2cc(C)c(=O)[nH]c2=O)C[C@H]1OS(C)(=O)=O | null | 80 | null |
579,316 | ord_dataset-a9ba4801408c4b01922886164c10a391 | null | 2003-01-01T00:01:00 | true | F[B-](F)(F)F.[CH3:6][C:7]1[CH:12]=[C:11]([CH3:13])[C:10]([CH3:14])=[CH:9][C:8]=1[C:15]1[CH:20]=[C:19]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:18]=[C:17]([C:27]2[CH:32]=[C:31]([CH3:33])[C:30]([CH3:34])=[CH:29][C:28]=2[CH3:35])[O+]=1.[PH3:36]>C(O)CCC>[CH3:6][C:7]1[CH:12]=[C:11]([CH3:13])[C:10]([CH3:14])=[CH:9][C:8]=1[C:15]1[CH:20]=[C:19]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:18]=[C:17]([C:27]2[CH:32]=[C:31]([CH3:33])[C:30]([CH3:34])=[CH:29][C:28]=2[CH3:35])[P:36]=1 | Cc1cc(C)c(-c2cc(-c3ccccc3)cc(-c3cc(C)c(C)cc3C)[o+]2)cc1C | P | null | F[B-](F)(F)F | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCCCO | null | null | null | null | null | null | null | null | null | null | null | null | 2.1 g (4.4 mmol) of 2,6-bis(2,4,5-trimethylphenyl)-4-phenylpyrylium tetrafluoroborate in 150 ml of n-butanol were used as starting material. The autoclave product obtained after the reaction with PH3 was evaporated to about 50 ml under reduced pressure at about 80° C. The solid which precipitated was filtered off with suction, washed with n-pentane and subsequently dissolved in toluene. The toluene solution was then washed with water until the aqueous phase was neutral. After removing the solvent and washing with a little n-pentane, the residue was dissolved in dichloromethane. The resulting solution was diluted with methanol and then evaporated under reduced pressure at 30° C. until a solid precipitated. The solid was filtered off with suction, washed with a little n-pentane and subsequently dried in a high vacuum. Yield: 0.8 g (45%) of light-yellow solid. | Cc1cc(C)c(-c2cc(-c3ccccc3)cc(-c3cc(C)c(C)cc3C)p2)cc1C | null | null | null |
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