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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797,856 | ord_dataset-a2d74266062e4398bc26c4f876903ab8 | null | 2007-01-01T00:11:00 | true | [CH3:1][O:2][CH2:3][C:4]([NH:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][C:15]=1Br)[CH:12]([NH:17][C:18]1[CH:30]=[CH:29][C:21]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[CH:20][CH:19]=1)[CH2:11][CH2:10]2)=[O:5].[Cu][C:32]#[N:33].N>CN1C(=O)CCC1>[CH3:1][O:2][CH2:3][C:4]([NH:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][C:15]=1[C:32]#[N:33])[CH:12]([NH:17][C:18]1[CH:30]=[CH:29][C:21]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[CH:20][CH:19]=1)[CH2:11][CH2:10]2)=[O:5] | N#C[Cu] | COCC(=O)Nc1cc2c(cc1Br)C(Nc1ccc(C(=O)OC(C)(C)C)cc1)CC2 | null | N | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN1CCCC1=O | null | null | null | null | null | null | null | null | null | null | 25 | 2 | To a solution of tert-butyl 4-[N-(5-methoxyacetamido-6-bromoindan-1-yl)amino]benzoate (0.714 g, 1.50 mol) in NMP (8 ml) [1-methyl-2-pyrrolidone] was added copper (I) cyanide (0.230 g, 2.55 mmol). The reaction mixture was placed in an oil-bath preheated to 140° C. and stirred at this temperature for 2 h. More copper (I) cyanide (0.100 g, 1.10 mmol) was then added and stirring was continued for a longer 3 hours. The reaction mixture was allowed to cool to room temperature, then poured into a mixture of aqueous ammonia (d=0.88, 7 ml) and ice (˜20 ml) and the resulting brown mixture was stirred at room temperature for ˜5 min. The brown solid was collected by filtration washed with plenty of water, then suspended in dichloromethane (100 ml). The mixture was stirred at room temperature for 10 min, dried (Na2SO4), and concentrated in vacuo. Purification by column chromatography, on elution with 35% ethyl acetate in hexane, afforded an off white solid that was reprecipitated from dichloromethane-ethyl acetate/hexane: 0.328 g, (52%) m.p. 163-164° C. 1H-NMR (250 MHz, DMSO-d6, TMS) 1.50 (s, 9H, C(CH3)3), 1.85, 2.58 (2×m, 2H, indanyl 2-H), 2.89 (m, 2H, indanyl 3-H), 3.41 (s, 3H, OCH3), 4.05 (s, 2H, CH2OMe), 5.06 (m, 1H, indanyl 1-H), 6.73 (d, J=8.82 Hz, 2H, 3,5-H), 6.82 (d, J=8.37 Hz, 1H, N10—H), 7.59, 7.57 (2×s, each 1H, indanyl 4-H, 7-H), 7.66 (d, J=8.77 Hz, 2,6-H), 9.88 (s, 1H, CONH), MS (ESI, m/z) 444 {(M+Na)+, 100%}; Found: C, 68.21; H, 6.47; N, 9.81; C24H27N3O4 requires C, 68.39; H, 6.46; N, 9.97%. | COCC(=O)Nc1cc2c(cc1C#N)C(Nc1ccc(C(=O)OC(C)(C)C)cc1)CC2 | null | null | null |
726,031 | ord_dataset-0387783899c642a8b7eb4ba379bcdf5d | null | 2006-01-01T00:08:00 | true | [CH2:1]([N:4]([CH2:8][C:9]1[S:13][C:12]([C:14]([OH:16])=O)=[CH:11][CH:10]=1)[CH2:5][CH:6]=[CH2:7])[CH:2]=[CH2:3].C(N1C=CN=C1)(N1C=CN=C1)=O.[C:29]([NH:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1[NH2:43])([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30]>C1COCC1>[C:32]([O:31][C:29](=[O:30])[NH:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1[NH:43][C:14]([C:12]1[S:13][C:9]([CH2:8][N:4]([CH2:1][CH:2]=[CH2:3])[CH2:5][CH:6]=[CH2:7])=[CH:10][CH:11]=1)=[O:16])([CH3:35])([CH3:33])[CH3:34] | CC(C)(C)OC(=O)Nc1ccccc1N | C=CCN(CC=C)Cc1ccc(C(=O)O)s1 | null | O=C(n1ccnc1)n1ccnc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | 25 | 0.75 | To a solution of 2.70 g (11.38 mmol) 5-diallylaminomethyl-thiophene-2-carboxylic acid in 50 ml THF was added 2.03 g (12.51 mmol) carbonyldiimidazol. After 45 min at rt, 2.48 g (11.95 mmol) mono-boc-ortho-phenylenediamine were added to the reaction mixture, and it was stirred for 3 h at rt. The solvent was evaporated and the residue dissolved in ethyl acetate. The organic phase was washed twice with sat. NaHCO3, once with water and dried over Na2SO4. The solvent was evaporated and the residue was subjected to silica gel chromatography (ethyl acetate/heptane 2:8) to yield 4.10 g (9.59 mmol) {2-[(5-Diallylaminomethyl-thiophene-2-carbonyl)-amino]-phenyl}-carbamic acid t-butyl ester; exact MW [M+H] calc'd: 428.20; MW found [M+H]: 428.3. | C=CCN(CC=C)Cc1ccc(C(=O)Nc2ccccc2NC(=O)OC(C)(C)C)s1 | null | 84.3 | null |
1,370,799 | ord_dataset-d23f2f15886d4c22b7d7ba5f0e203e81 | null | 2013-01-01T00:12:00 | true | [H-].[Na+].[C:3]([O:11][CH2:12][CH3:13])(=[O:10])[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].Cl[C:15]1[N:20]=[CH:19][CH:18]=[CH:17][N:16]=1>CN(C)C=O>[N:16]1[CH:17]=[CH:18][CH:19]=[N:20][C:15]=1[CH:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[C:3]([O:11][CH2:12][CH3:13])=[O:10] | Clc1ncccn1 | CCOC(=O)CC(=O)OCC | null | [H-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | 25 | 0.5 | 4.80 g of sodium hydride (55% oil dispersion) was suspended in 50 ml of N,N-dimethylformamide. Into this, 17.60 g of diethyl malonate was added dropwise over a period of about 0.5 hours at room temperature under a nitrogen atmosphere. The mixture was stirred further for 0.5 hours at the same temperature, then, to the mixture was added 5.73 g of 2-chloropyrimidine. The mixture was stirred for 3 hours at 100° C. The reaction mixture was allowed to cool to room temperature. To the reaction mixture was added ice water, and extracted with ethyl acetate. The organic layer was washed with saturated brine three times, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. 18.84 g of the resultant residue was subjected to silica gel column chromatography, to obtain 5.09 g of diethyl (2-pyrimidinyl)malonate. | CCOC(=O)C(C(=O)OCC)c1ncccn1 | null | 42.7 | null |
562,508 | ord_dataset-7c28974b7fcf4c9c86d5f2a42ba328a2 | null | 2002-01-01T00:09:00 | true | C([NH:5][C:6]([NH:8][C@@H:9]([CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([N+:19]([O-:21])=[O:20])[CH:14]=1)[CH2:10]O)=[S:7])(C)(C)C.[ClH:22]>>[ClH:22].[N+:19]([C:15]1[CH:14]=[C:13]([CH:18]=[CH:17][CH:16]=1)[CH2:12][C@H:9]1[CH2:10][S:7][C:6]([NH2:5])=[N:8]1)([O-:21])=[O:20] | CC(C)(C)NC(=S)N[C@H](CO)Cc1cccc([N+](=O)[O-])c1 | null | 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 | 7 | The process is performed as in Example 2, starting with N-(tert-butyl)-N′-[(1S)-2-hydroxy-1-(3-nitrobenzyl)ethyl]thiourea in 80 cm3 of aqueous 6N hydrochloric acid. The heating time is 7 hours. The product is isolated in an identical manner and then purified by chromatography under an argon pressure of 80 kPa, on a column of silica gel (particle size 40-63μ; diameter 3.5 cm; height 30 cm), eluting with a dichloromethane/methanol mixture (95/5 by volume). The fractions corresponding to the expected product are collected. These fractions are combined and then concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. 3.90 g of (−)-(4S)-4-(3-nitrobenzyl)-4,5-dihydro-1,3-thiazol-2-ylamine hydrochloride are obtained in the form of a white solid melting at 220° C. (αD20=−18.4±0.05 at a concentration of 0.5% in methanol). | NC1=N[C@@H](Cc2cccc([N+](=O)[O-])c2)CS1 | null | null | null |
1,126,688 | ord_dataset-285df12e34cd46e993e3c8ebc3a8962a | null | 2012-01-01T00:01:00 | true | [C:1]([C:4]1[CH:18]=[CH:17][C:7]([O:8][CH2:9][C:10]([N:12]([CH2:15][CH3:16])[CH2:13][CH3:14])=[O:11])=[CH:6][CH:5]=1)(=O)[CH3:2].[CH2:19]([NH2:22])[CH2:20][NH2:21]>C(O)(=O)C>[NH2:21][CH2:20][CH2:19][NH:22][CH:1]([C:4]1[CH:18]=[CH:17][C:7]([O:8][CH2:9][C:10]([N:12]([CH2:15][CH3:16])[CH2:13][CH3:14])=[O:11])=[CH:6][CH:5]=1)[CH3:2] | NCCN | CCN(CC)C(=O)COc1ccc(C(C)=O)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(=O)O | null | null | null | null | null | null | null | null | null | null | null | null | By using 2-(4-acetylphenoxy)-N,N-diethylacetamide (250 mg), ethylenediamine (400 μl) and acetic acid (700 μl) as starting materials, the title compound (52.9 mg) was obtained in the same manner as that of Reference Example 64, (1). | CCN(CC)C(=O)COc1ccc(C(C)NCCN)cc1 | null | null | null |
294,858 | ord_dataset-bb4579c57ddc48c6a01fad97dacb6293 | null | 1994-01-01T00:08:00 | true | [CH2:1]([C:3]([CH2:22][CH3:23])([P:18]([OH:21])([OH:20])=[O:19])[C@H:4]1[CH2:13][CH2:12][C@@H:11]2[C@@H:6]([CH2:7][CH2:8][N:9]([C:14]([O:16][CH3:17])=[O:15])[CH2:10]2)[CH2:5]1)[CH3:2].[CH3:24][OH:25]>C1(C)C=CC(S([O-])(=O)=O)=CC=1.C([N+](CC)(CC)CC)C>[CH2:22]([C:3]([CH2:1][CH3:2])([P:18]([OH:20])([OH:21])=[O:19])[CH:4]1[CH2:13][CH2:12][CH:11]2[CH:6]([CH2:7][CH:8]([O:25][CH3:24])[N:9]([C:14]([O:16][CH3:17])=[O:15])[CH2:10]2)[CH2:5]1)[CH3:23] | CCC(CC)([C@H]1CC[C@H]2CN(C(=O)OC)CC[C@H]2C1)P(=O)(O)O | CO | null | CC[N+](CC)(CC)CC | Cc1ccc(S(=O)(=O)[O-])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 | Four carbon plate electrodes were immersed into a solution containing the compound from Example 1 (250 mg), tetraethylammonium p-toluenesulfonate (21 mg), in methanol (10 ml). A constant current of 0.5 A was applied to the electrodes. Additional methanol (7.8 ml) was added to the reaction to replace methanol which was lost due to evaporation. After 550 coulombs of current had passed, the electrodes were removed and the solution was added to 10% brine. This mixture was extracted with ether (3×15 ml). The combined ether extracts were washed with water and with brine, dried over magnesium sulfate, and concentrated in vacuo at room temperature to give 237 ml of the title compound as an oil. The material was stored in the refrigerator and used in the next step without further purification. | CCC(CC)(C1CCC2CN(C(=O)OC)C(OC)CC2C1)P(=O)(O)O | null | null | null |
1,739,566 | ord_dataset-eacfee6d16d8455a93348409f1b37be4 | null | 2016-01-01T00:06:00 | true | C([O:4][C:5](=[O:26])[CH2:6][CH2:7][CH2:8][C:9]1[N:13]([CH3:14])[C:12]2[CH:15]=[CH:16][C:17]([N:19]([CH2:23][CH2:24][Cl:25])[CH2:20][CH2:21][Cl:22])=[CH:18][C:11]=2[N:10]=1)(C)C.[ClH:27]>O>[CH3:14][N:13]1[C:9]([CH2:8][CH2:7][CH2:6][C:5]([OH:26])=[O:4])=[N:10][C:11]2[CH:18]=[C:17]([N:19]([CH2:20][CH2:21][Cl:22])[CH2:23][CH2:24][Cl:25])[CH:16]=[CH:15][C:12]1=2.[ClH:27] | CC(C)OC(=O)CCCc1nc2cc(N(CCCl)CCCl)ccc2n1C | null | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | null | null | null | null | null | null | null | null | null | null | 37.5 | 1 | 4-{5-[Bis-(2-chloroethyl)amino]-1-methyl-1H-benzimidazol-2-yl}-butyric acid isopropyl ester (3 g) is charged into a round bottom flask and 50% hydrochloric acid solution (21 mL) is slowly added. The mixture is heated to 35-40° C., maintained for about 90 minutes, and concentrated under vacuum at about 55-58° C., to give a viscous mass. Warm water (12 mL, 55-60° C.) is added and the mixture is stirred for about 1 hour. The obtained solid is collected by filtration, washed with water (3 mL), and dried under vacuum at 45-50° C. for 4 hours to give bendamustine hydrochloride. Yield: 2.2 g (75%). | Cn1c(CCCC(=O)O)nc2cc(N(CCCl)CCCl)ccc21 | null | null | null |
1,251,797 | ord_dataset-c544c0c663f54dbea4ddb52ddde7934e | null | 2013-01-01T00:01:00 | true | C[O:2][C:3](=[O:18])[CH:4]([O:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([N:13]2[CH:17]=[N:16][N:15]=[N:14]2)[CH:8]=1)[CH3:5].[Li+].[OH-].O1CCOCC1>>[N:13]1([C:9]2[CH:8]=[C:7]([CH:12]=[CH:11][CH:10]=2)[O:6][CH:4]([CH3:5])[C:3]([OH:18])=[O:2])[CH:17]=[N:16][N:15]=[N:14]1 | COC(=O)C(C)Oc1cccc(-n2cnnn2)c1 | null | null | [Li+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1COCCO1 | null | null | null | null | null | null | null | null | null | null | 25 | 3 | To a 25 mL round-bottom flask equipped with a magnetic stir bar was added 2-(3-tetrazol-1-yl-phenoxy)-propionic acid methyl ester 30 (326 mg, 1.3 mmol, 1.0 eq.), 2N LiOH (2.6 mL, 2.6 mmol, 2.0 eq), and 1,4-dioxane (2.6 ml, 2.6 mmol, 2.0 eq). The reaction mixture was then stirred at room temperature for 3 hours. The reaction mixture was concentrated, diluted with water (5 mL), acidified with 1 N HCl (adjust pH=3.5), and then extracted with 3× EtOAc (25 mL each). The organic layer was dried with Na2SO4, concentrated, and dried under high vacuum to yield 2-(3-tetrazol-1-yl-phenoxy)-propionic acid 31 (230.3 mg, 98% yield). LC/MSD (HP Series 1100 MSD) MS (ES+) m/z 235.0 (M+H)+1 1H-NMR, Varian 400 MHz (MeOH-d4) δ 9.76 (s, 1H), 7.52 (t, 1H), 7.45 (d, 2H), 7.08 (d, 1H), 4.93 (q, 1H), 1.62 (d, 3H) ppm. | CC(Oc1cccc(-n2cnnn2)c1)C(=O)O | null | 75.6 | null |
815,804 | ord_dataset-50f99930fc41474db226bc80774b38df | null | 2008-01-01T00:04:00 | true | [OH:1][C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][C:12]=1[OH:13])[CH:5]=[CH:6][C:7]([OH:9])=[O:8]>S(Cl)(Cl)=O>[C:7]([OH:9])(=[O:8])/[CH:6]=[CH:5]/[C:4]1[CH:10]=[CH:11][C:12]([OH:13])=[C:2]([OH:1])[CH:3]=1 | O=C(O)C=Cc1ccc(O)c(O)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O=S(Cl)Cl | null | null | null | null | null | null | null | null | null | null | 50 | 5 | 3,4-Dihydroxycinnamic acid (1.13 g, 6.27 mmole) was dissolved in thionyl chloride (25 ml) and the solution was stirred for 5 hours at 40-60° C. The solvent was removed, the residue was dissolved in thoroughly dried ethyl acetate and the solution was slowly added to a solution of 5-methoxy tryptamine (1.2 g) in benzene, which contained also ethylamine (1 ml). The mixture was stirred overnight, water (10 ml) was added and the mixture again stirred for 15 minutes. The solvents were removed, the residue was dissolved in ethyl acetate and the solution was washed successively with water, saturated NaHCO3 solution, water and brine, and then dried over Na2SO4. The solvent was removed and the product was purified by column chromatography using 1:9 methanol/dichloromethane. The purification process was repeated three times to remove byproducts. The fraction identified as the caffeic acid 5-methoxytryptamide was further purified by recrystallization from ethyl acetate/hexane solution. The compound was obtained as white crystals (yield about 60%). | O=C(O)/C=C/c1ccc(O)c(O)c1 | null | 60 | null |
372,730 | ord_dataset-ee5599340390470d8e5b5ac1feddf9d6 | null | 1997-01-01T00:08:00 | true | [C:1]([NH:4][CH:5]([O:16]CC)[C:6]([NH:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:7])(=[O:3])[CH3:2].B(F)(F)F.CCOCC.O.C([O-])(O)=O.[Na+]>>[C:1]([NH:4][CH:5]([OH:16])[C:6]([NH:8][CH2:9][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)=[O:7])(=[O:3])[CH3:2] | CCOC(NC(C)=O)C(=O)NCc1ccccc1 | null | null | FB(F)F | O=C([O-])O | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOCC | O | null | null | null | null | null | null | null | null | null | null | null | Reacting 2-acetamido-N-benzyl-2-ethoxyacetamide (1.00 g, 4.0 mmol), BF3.Et2O (0.91 g, 6.4 mmol) and H2O (0.12 g, 6.7 mmol) followed by aqueous NaHCO3 workup gave an aqueous reaction mixture. The solution was then extracted with EtOAc (3×50 mL), and the combined EtOAc extracts were dried (Na2SO4), and concentrated in vacuo. The residue was purified by flash column chromatography on SiO2 gel (3% MeOH/CHCl3) to give the desired product as a white solid. | CC(=O)NC(O)C(=O)NCc1ccccc1 | null | null | null |
868,169 | ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b | null | 2009-01-01T00:03:00 | true | [Br:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([NH:12][CH3:13])=[CH:9][CH:10]=2)[C:5](=[O:14])[N:4]([CH:15]([CH3:17])[CH3:16])[N:3]=1.[H-].[Na+].[CH3:20][S:21][CH2:22][CH2:23]Cl.O>CN(C=O)C>[Br:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([N:12]([CH3:13])[CH2:23][CH2:22][S:21][CH3:20])=[CH:9][CH:10]=2)[C:5](=[O:14])[N:4]([CH:15]([CH3:17])[CH3:16])[N:3]=1 | CSCCCl | CNc1ccc2c(Br)nn(C(C)C)c(=O)c2c1 | null | [H-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | O | null | null | null | null | null | null | null | null | null | 25 | 0.5 | 4-Bromo-2-isopropyl-7-methylamino-2H-phthalazin-1-one (0.095 g, 0.32 mmol) was dissolved in DMF (5 ml). To this was added NaH (60%, 0.015 g, 0.38 mmol) as a suspension in DMF (2 ml). The mixture was stirred at RT for 30 min then chloroethyl methyl sulfide (0.042 g, 0.38 mmol) was added in one portion as a solution in DMF (1 ml) and the reaction mixture was heated to 70° C. for 24 hours. After this time, the reaction mixture was cooled to RT and water (10 ml) was added cautiously, the mixture was extracted with EtOAc (3×10 ml), the organic layers were combined, dried (MgSO4), filtered and concentrated under vacuum. Flash column chromatography (elution: 70% hexane, 30% EtOAc) gave the title compound (0.021 g, 18% yield) as a white solid. δH (400 MHz, CDCl3), 7.73 (1H, d), 7.48 (1H, d), 7.13 (1 H, d), 5.41-5.29 (1H, m), 3.71 (2H, t), 3.18 (3H, s), 3.15 (3H, s), 2.73 (2H, t), 1.41 (6H, d). | CSCCN(C)c1ccc2c(Br)nn(C(C)C)c(=O)c2c1 | null | 17.7 | null |
1,770,361 | ord_dataset-0b32b90cc77b4a3db47ad263e0bbc1a8 | null | 2016-01-01T00:09:00 | true | [Br:1][C:2]1[S:23][C:5]2[N:6]([CH3:22])[C:7](=[O:21])[N:8]([CH2:11][CH2:12][CH2:13][O:14][CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][O:16]3)[C:9](=[O:10])[C:4]=2[C:3]=1[CH2:24]Br.CS(C)=[O:28]>CC(=O)OCC.O>[Br:1][C:2]1[S:23][C:5]2[N:6]([CH3:22])[C:7](=[O:21])[N:8]([CH2:11][CH2:12][CH2:13][O:14][CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][O:16]3)[C:9](=[O:10])[C:4]=2[C:3]=1[CH:24]=[O:28] | Cn1c(=O)n(CCCOC2CCCCO2)c(=O)c2c(CBr)c(Br)sc21 | CS(C)=O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CCOC(C)=O | null | null | null | null | null | null | null | null | null | 50 | null | To a solution of 6-bromo-5-(bromomethyl)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl) thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (1.7 g, 3.43 mmol) in DMSO (20 mL) was added IBX (1.92 g, 6.85 mmol). The reaction was heated at 50° C. for 2 h, cooled to RT then diluted with EA (80 mL) and water (50 mL). The organic layer was dried over Na2SO4 and concentrated to a residue which was purified by chromatography eluted with PE/EA (5:1) to give 6-bromo-1-methyl-2,4-dioxo-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carbaldehyde (500 mg, 33.8% yield) as a yellow oil. LCMS: MH+ 431 and TR=1.313 min. | Cn1c(=O)n(CCCOC2CCCCO2)c(=O)c2c(C=O)c(Br)sc21 | null | 33.8 | null |
1,385,553 | ord_dataset-31641fb65b34430fa7435229b949b604 | null | 2014-01-01T00:01:00 | true | [N:1]([CH:4]1[CH2:13][CH2:12][C:11]2[CH:10]=[C:9]([C:14]#[N:15])[CH:8]=[CH:7][C:6]=2[C:5]1=[O:16])=[N+:2]=[N-:3].O.[BH4-].[Na+]>C1COCC1>[N:1]([CH:4]1[CH2:13][CH2:12][C:11]2[CH:10]=[C:9]([C:14]#[N:15])[CH:8]=[CH:7][C:6]=2[CH:5]1[OH:16])=[N+:2]=[N-:3] | N#Cc1ccc2c(c1)CCC(N=[N+]=[N-])C2=O | null | null | [BH4-] | [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 | 0 | 0.75 | Racemic 6-azido-5-oxo-5,6,7,8-tetrahydronaphthalene-2-carbonitrile (28 mg, 0.13 mmol) was dissolved in THF (1253 mL) and water (66.0 mL) at 0° C. To this solution was added sodium borohydride (6.49 mg, 0.17 mmol). The resulting solution was stirred at 0° C. for 45 min. After that, the reaction was quenched by several drops of 1N HCl. The mixture was loaded to an ISCO 13 g column directly and purified by ISCO Combiflash Companion (10% ethyl acetate-hexane for 3 min then ramp to 50% ethyl acetate-hexane over 7 min then 20% ethyl acetate-hexane for 5 more min, product came out 8-10 min) to afford racemic (5S*,6R*)-6-azido-5-hydroxy-5,6,7,8-tetrahydronaphthalene-2-carbonitrile (15.0 mg, 0.07 mmol, 53.1%) as a white solid. NMR showed that the product was a mixture of around 6:1 two diastereomers; LCMS=215.22 [M+H]+. | N#Cc1ccc2c(c1)CCC(N=[N+]=[N-])C2O | null | 53.8 | null |
1,367,331 | ord_dataset-d932d1d683704a8bad3d064bcb197acc | null | 2013-01-01T00:11:00 | true | [I:1][C:2]1[CH:3]=[N:4][NH:5][CH:6]=1.[H-].[Na+].[CH2:9]1[CH2:13]O[CH2:11][CH2:10]1>>[CH2:13]([N:4]1[CH:3]=[C:2]([I:1])[CH:6]=[N:5]1)[CH2:9][CH2:10][CH3:11] | Ic1cn[nH]c1 | C1CCOC1 | null | [H-] | [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 | 70 | 8 | To a stirred suspension of 4-iodopyrazole (0.3 g, 1.55 mmol) and 60% NaH (0.08 g, 2 mmol) in anhydrous THF (1 ml) butyl bromide (0.5 ml) was added and the mixture was stirred overnight at 70° C. The mixture was quenched with saturated NH4Cl and extracted with EtOAc (50 ml). The organic layer was washed with H2O, dried over MgSO4 and filtered. The filtrate was distilled off and the residue was dried in vacuo to give 1-butyl-4-iodo-1H-pyrazole (0.39 g, 100%), as colourless oil. 1H NMR (CDCl3) 7.47 (s, 1H); 7.39 (s, 1H); 4.09 (t, 2H, J=7.14 Hz); 1.85-1.75 (m, 2H); 1.35-1.23 (m, 2H); 0.91 (t, 3H, J=7.32 Hz). To a stirred solution of the above product (0.36 g, 1.44 mmol) in anhydrous THF (0.5 ml) 2M iPrMgCl in THF (2 ml) was added at 0° C. and after warming up to room temperature anhydrous DMF (1 ml) was added to it. This was stirred for 1 h at room temperature, than quenched with saturated NH4Cl and extracted with EtOAc (30 ml). The organic layer was washed with H2O, dried over MgSO4 and filtered. The filtrate was evaporated to dryness to give 1-butyl-1H-pyrazole-4-carbaldehyde (0.27 g; 100%), as pale oil. 1H NMR (CDCl3) 9.82 (s, 1H); 7.93 (s, 1H); 7.89 (s, 1H); 4.13 (t, 2H, J=7.11 Hz); 1.9-1.8 (m, 2H); 1.4-1.22 (m, 2H); 0.92 (t, 3H, J=7.29 Hz). To a stirred solution of above aldehyde (0.22 g, 1.44 mmol) in the mixture of dioxane and H2O (15 ml: 3 ml) KMnO4 (0.25 g; 1.58 mmol) was added over a period of 30 min. The mixture was evaporated to dryness and the residue was treated in the mixture of EtOAc and MeOH (20 ml: 5 ml) and filtered through Celite pad. The filtrate was evaporated to dryness to give the title compound (0.24 g; 100%), as creamy crystalline solid. 1H NMR (CDCl3) 7.8 (s, 1H); 7.56 (b, 1H); 4.05 (b, 2H); 1.7 (b, 2H); 1.18 (b, 2H); 0.83 (b, 3H). | CCCCn1cc(I)cn1 | null | 100 | null |
628,938 | ord_dataset-0a66204fc43e49c2922e6f9107e6b62f | null | 2004-01-01T00:03:00 | true | [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:33]=[CH:34][C:35]=1[O:36][CH3:37])[CH2:6][CH:7]1[C:16]2[C:11](=[CH:12][C:13]([O:18][CH3:19])=[C:14]([OH:17])[CH:15]=2)[CH2:10][CH2:9][N:8]1[CH2:20][C:21]([NH:23][CH:24]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH2:26][CH2:25]1)=[O:22].[CH2:38](Br)[CH2:39][CH2:40][CH3:41]>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:33]=[CH:34][C:35]=1[O:36][CH3:37])[CH2:6][CH:7]1[C:16]2[C:11](=[CH:12][C:13]([O:18][CH3:19])=[C:14]([O:17][CH2:38][CH2:39][CH2:40][CH3:41])[CH:15]=2)[CH2:10][CH2:9][N:8]1[CH2:20][C:21]([NH:23][CH:24]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH2:26][CH2:25]1)=[O:22] | COc1cc2c(cc1O)C(Cc1ccc(OC)c(OC)c1)N(CC(=O)NC1CCc3ccccc31)CC2 | CCCCBr | null | null | null | null | null | null | null | 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 by reaction of 2-[1-(3,4-dimethoxy-benzyl)-7-hydroxy-6-methoxy-3,4-dihydro-1H-isoquinolin-2-yl]-N-(indan-1-yl)-acetamide with butyl bromide | CCCCOc1cc2c(cc1OC)CCN(CC(=O)NC1CCc3ccccc31)C2Cc1ccc(OC)c(OC)c1 | null | null | null |
658,546 | ord_dataset-be508e976bbb4586a0cc3368302a62f8 | null | 2005-01-01T00:01:00 | true | [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1.C[Al](C)C.C([O:15][C:16]([C:18]1[NH:22][N:21]=[C:20]([CH3:23])[CH:19]=1)=O)C>C(Cl)Cl>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([NH:1][C:16]([C:18]2[NH:22][N:21]=[C:20]([CH3:23])[CH:19]=2)=[O:15])=[N:3][CH:4]=1 | Nc1ccc(Br)cn1 | CCOC(=O)c1cc(C)n[nH]1 | null | C[Al](C)C | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | null | 4 | A solution of 2-amino-5-bromopyridine (0.200 g, 1.16 mmol 1.0 equiv), in 5 mls of methylene chloride, under argon, was treated with trimethylaluminum (0.312 mL, 2.0 N in hexanes, 4.0 equiv) at room temperature for 30 min. To the solution was added ethyl-3-methylpyrazole-5-carboxylate (0.356 g, 2.0 equiv). After 4 hrs, the volatile was evaporated, and the residue was redissolved into EtOAc, washed with 0.5N HCl, 0.2 N K2CO3, and saturated aqueous NaCl. The organic layer was dried over Na2SO4, filtered, evaporated and purified via flash chromatography on silica gel to give N-(5-bromo-2-pyridinyl)-(3-methyl)5-pyrazolecarboxamide (0.160 g, 49%). MS found for C10H9BrN4O (M+H)+: 281, 283. Step 2: A solution of N-(5-bromo-2-pyridinyl)-(3-methyl)5-pyrazolecarboxamide (0.060 g, 0.213 mmol, 1.0 equiv) in 2 mL of acetonitrile was treated with triphosgene (0.063 g, 1.0 equiv) at room temperature for 5 min under argon. To the solution was added 4-[(2-t-butylaminosulfonyl)phenyl]phenylamine (0.071 g, 1.1 equiv) After 1 hr, the volatile was evaporated and the residue was redissolved into EtOAc, washed with 0.5N HCl, 0.2 N K2CO3, and saturated aqueous NaCl. The organic layer was dried over Na2SO4, filtered, evaporated, purified via flash chromatography on silica gel and then reacted in 2 mL of trifluoroacetic acid for 16 hrs at room temperature. TFA was then evaporated and the residue was redissolved into EtOAc, washed with 0.5N HCl, 0.2 N K2CO3, and saturated aqueous NaCl. The organic layer was dried over Na2SO4, filtered, evaporated, and triturated with diethyl ether to give N-(5-bromo-2-pyridinyl)-(2-4-[(2-aminosulfonyl)phenyl]phenylaminocarbonyl)5-methyl-pyrazolcarboxamide (0.0024 g, 2%). MS found for C23H19BrN6O4S (M+H)+: 555, 557. | Cc1cc(C(=O)Nc2ccc(Br)cn2)[nH]n1 | null | 49.1 | null |
176,670 | ord_dataset-07db50a3ce6941919df30a9e2898988f | null | 1988-01-01T00:08:00 | true | [OH:1][CH:2]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:3]1[C:8]2[S:9][C:10]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[C:11](COC)[C:7]=2[CH:6]=[CH:5][N:4]=1.C[OH:28]>Cl>[OH:1][CH:2]([C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)[C:3]1[C:8]2[S:9][C:10]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[C:11]([OH:28])[C:7]=2[CH:6]=[CH:5][N:4]=1 | CO | COCc1c(-c2ccccc2)sc2c(C(O)c3ccccc3)nccc12 | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | A solution of 0.61 g (1.8 mmol) of 7-(hydroxyphenylmethyl)-3-methoxymethyl-2-phenyl-6-azabenzo[b]thiophene in 2.7 mL of 2M HCl and 2.7 mL of methanol was heated at reflux for 30 minutes. The solution was cooled and partitioned between ethyl acetate and water. The ethyl acetate layer was dried and concentrated to afford 0.50 g (93%) of white solid, m.p. 214°-215° C. | Oc1c(-c2ccccc2)sc2c(C(O)c3ccccc3)nccc12 | null | 93 | null |
516,790 | ord_dataset-a495451286334c5c9bbcbd48a00c1350 | null | 2001-01-01T00:09:00 | true | C[O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[NH:13][C:12]([C:14]3[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=3)=[N:11][C:10]=2[C:23]([NH:25][C:26]2[S:27][CH:28]=[CH:29][N:30]=2)=[O:24])=[CH:5][CH:4]=1.B(Br)(Br)Br.O>ClCCl>[OH:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[NH:13][C:12]([C:14]3[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=3)=[N:11][C:10]=2[C:23]([NH:25][C:26]2[S:27][CH:28]=[CH:29][N:30]=2)=[O:24])=[CH:5][CH:4]=1 | COc1ccc(-c2[nH]c(-c3ccc([N+](=O)[O-])cc3)nc2C(=O)Nc2nccs2)cc1 | null | null | BrB(Br)Br | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | ClCCl | null | null | null | null | null | null | null | null | null | null | 24 | 5-(4-Methoxyphenyl)-2-(4-nitrophenyl)-N-(2-thiazolyl)-imidazole-4-carboxamide (2.1 g) obtained in Example 47 was dissolved in dichloromethane (210 ml) and boron tribromide (3 ml) was added. The mixture was stirred for one day. The reaction mixture was poured into cold water and the precipitated crystals were collected by filtration to give 5-(4-hydroxyphenyl)-2-(4-nitrophenyl)-N-(2-thiazolyl)-imidazole-4-carboxamide (1.7 g). | O=C(Nc1nccs1)c1nc(-c2ccc([N+](=O)[O-])cc2)[nH]c1-c1ccc(O)cc1 | null | 83.7 | null |
606,615 | ord_dataset-273fda773e864aaf9b71a30a2d9f2162 | null | 2003-01-01T00:08:00 | true | [C:1]1([CH:7]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[O:8][CH:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][NH:18][C:19]3[CH:20]=[CH:21][C:22]4[N:23]([C:25](=[O:28])[NH:26][N:27]=4)[N:24]=3)[CH2:11][CH2:10]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].Br[CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40]>CN(C)C=O>[C:29]1([CH:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[O:8][CH:9]2[CH2:10][CH2:11][N:12]([CH2:15][CH2:16][CH2:17][NH:18][C:19]3[CH:20]=[CH:21][C:22]4[N:23]([C:25](=[O:28])[N:26]([CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40])[N:27]=4)[N:24]=3)[CH2:13][CH2:14]2)[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1 | CCOC(=O)CBr | O=c1[nH]nc2ccc(NCCCN3CCC(OC(c4ccccc4)c4ccccc4)CC3)nn12 | null | [H-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | 25 | 1 | 0.550 g of 6-[3-[4-(diphenylmethoxy)piperidino]propylamino][1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one was suspended in 3 ml of N,N-dimethylformamide; 0.058 g of 60% oily sodium hydride was added, followed by stirring at room temperature for 1 hour. Under ice cooling, 0.160 ml of ethyl bromoacetate was added, followed by stirring at room temperature for 2 hours. After ice water was added, the reaction mixture was extracted with ethyl acetate; the extract was washed with saturated saline and dried over magnesium sulfate. After concentration under reduced pressure, the residue was subjected to silica gel column chromatography and eluted with ethyl acetate-methanol-triethylamine (90:10:1). The desired fraction was collected and concentrated; the crystal obtained was filtered, washed with diethyl ether, and dried, to yield 0.332 g of the title compound. | CCOC(=O)Cn1nc2ccc(NCCCN3CCC(OC(c4ccccc4)c4ccccc4)CC3)nn2c1=O | null | null | null |
1,354,861 | ord_dataset-6034127657614f02860ed057b62b882e | null | 2013-01-01T00:10:00 | true | [CH2:1]([C:9]1[N:10]=[C:11]2[C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=3[NH:15][C:14]3[N:22]=[CH:23][CH:24]=[CH:25][C:13]=3[N:12]2[CH:26]=1)[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Br:27]N1C(=O)CCC1=O>C1COCC1>[Br:27][C:26]1[N:12]2[C:13]3[CH:25]=[CH:24][CH:23]=[N:22][C:14]=3[NH:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[C:11]2=[N:10][C:9]=1[CH2:1][CH2:2][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1 | c1ccc(CCc2cn3c(n2)-c2ccccc2Nc2ncccc2-3)cc1 | O=C1CCC(=O)N1Br | 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 | 25 | 0.5 | To a solution 2-phenethyl-9H-benzo[f]imidazo[1,2-d]pyrido[2,3-b][1,4]diazepine (0.374 g, 1 eq.) in THF (50 mL) was added N-bromosuccinimide (0.206 g, 1.05 eq.). The reaction was stirred at room temperature for 30 minutes, poured onto water (100 mL) and extracted with dichloromethane (2×100 mL). The organic extracts were combined, washed with brine (1×50 mL) and dried over sodium sulfate. After filtration and concentration under reduced pressure, the crude product, 3-bromo-2-phenethyl-9H-benzo[f]imidazo[1,2-d]pyrido[2,3-b][1,4]diazepine (0.197 g, 42%) was obtained as an orange solid. LCMS: 419 [M+H]. | Brc1c(CCc2ccccc2)nc2n1-c1cccnc1Nc1ccccc1-2 | null | 42.7 | null |
516,824 | ord_dataset-a495451286334c5c9bbcbd48a00c1350 | null | 2001-01-01T00:09:00 | true | [Cl:1][C:2]1[CH:3]=[C:4]([S:8]([N:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH:13]=[C:12]2[C:20]([O:22]C)=[O:21])(=[O:10])=[O:9])[CH:5]=[CH:6][CH:7]=1.[I-].[Li+].Cl>N1C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([S:8]([N:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH:13]=[C:12]2[C:20]([OH:22])=[O:21])(=[O:9])=[O:10])[CH:5]=[CH:6][CH:7]=1 | COC(=O)c1cc2ccccc2n1S(=O)(=O)c1cccc(Cl)c1 | null | null | Cl | [I-] | [Li+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | c1ccncc1 | null | null | null | null | null | null | null | null | null | null | 25 | null | Methyl N-(3-chlorophenylsulphonyl)indole-2-carboxylate (0.56 g) and lithium iodide (2.0 g) were dissolved in pyridine and heated at reflux for 6 hours, cooled to room temperature and poured into 2M HCl and extracted with diethyl ether. Combined organic extracts were dried (MgSO4) and concentrated in vacuo to give an oil which was purified by column chromatography using DCM-2% methanol as eluent to give the desired product as a white solid (0.24 g, 45%), mp 216-217°; NMR δ (CD3SOCD3) 7.30-8.10 (m, 9H); M/z(−) 334 (M−H+), 290, 226, 191, 180, 116. | O=C(O)c1cc2ccccc2n1S(=O)(=O)c1cccc(Cl)c1 | null | 44.6 | null |
661,325 | ord_dataset-04d607efe1d9485eb99fafa06880f62e | null | 2005-01-01T00:02:00 | true | N1C=CC=CC=1.[NH2:7][C:8]1[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[C:10]([Cl:18])[CH:9]=1.[CH3:19][N:20]([CH3:25])[S:21](Cl)(=[O:23])=[O:22]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH3:19][N:20]([CH3:25])[S:21]([NH:7][C:8]1[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[C:10]([Cl:18])[CH:9]=1)(=[O:23])=[O:22] | CN(C)S(=O)(=O)Cl | COC(=O)c1ccc(N)cc1Cl | null | CN(C)c1ccncc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | c1ccncc1 | ClCCl | null | null | null | null | null | null | null | null | null | 25 | 16 | Pyridine (0.4 mL) was added to a solution of methyl 4-amino-2-chlorobenzoate (0.3 g) in CH2Cl2 (10 mL) at 0° C. under N2. N,N-Dimethylsulfamoyl chloride (0.21 mL) was added and the mixture was stirred at room temperature for 16 hours and refluxed for 5 hours. DMAP (0.4 g) was added and the mixture was stirred for 3 hours. The mixture was diluted with CH2Cl2 (100 mL), washed successively with 1N HCl, brine, satd. NaHCO3 and brine, dried and evaporated. The residue was purified by flash column chromatography (silica gel; eluent: EtOAc/hexane 1:3) to give 0.31 g of methyl 4-(N,N-dimethylsulfamoyl)amino-2-chlorobenzoate. ESMS: m/z 293 (MH+) | COC(=O)c1ccc(NS(=O)(=O)N(C)C)cc1Cl | null | null | null |
1,211,261 | ord_dataset-dc3bb1b1ac4e4229a3fc28fb559a9777 | null | 2012-01-01T00:10:00 | true | [CH2:1]([O:4][CH2:5][C:6]([CH2:17][OH:18])([CH2:12][O:13][CH2:14][CH:15]=[CH2:16])[CH2:7][O:8][CH2:9][CH:10]=[CH2:11])[CH:2]=[CH2:3].[H-].[Na+].[CH2:21](Br)[CH:22]=[CH2:23]>C1COCC1>[CH2:9]([O:8][CH2:7][C:6]([CH2:17][O:18][CH2:23][CH:22]=[CH2:21])([CH2:12][O:13][CH2:14][CH:15]=[CH2:16])[CH2:5][O:4][CH2:1][CH:2]=[CH2:3])[CH:10]=[CH2:11] | C=CCOCC(CO)(COCC=C)COCC=C | C=CCBr | 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 | 30.7 g (0.12 mol) of pentaerythritol triallylether was dissolved in 100 ml of dry THF and 4.4 g (0.18 mol) of NaH was added in small portions while stirring. After gas evolution had ceased, 16 ml (0.18 mol) of allyl bromide was added and the reaction mixture was stirred overnight at room temperature. In order to drive the reaction to completion, it was subsequently brought to reflux and stirred for 1 hr. The precipitated salts were removed by filtration over ca. 1 cm of Celite 545 and the solvent and excess allyl bromide were evaporated, yielding 35.3 g (99.5%) of a pale yellow oil. The raw product was dissolved in 100 ml of diethyl ether and washed subsequently with 50 ml of 0.1 M aqueous KHSO4 and 50 ml of saturated aqueous NaHCO3 solution. Drying the organic layer with MgSO4 and evaporation of the solvent yielded 34.4 g (97%) of the pure product. | C=CCOCC(COCC=C)(COCC=C)COCC=C | null | 99.2 | null |
1,353,569 | ord_dataset-6034127657614f02860ed057b62b882e | null | 2013-01-01T00:10:00 | true | Cl.[CH2:2]([O:9][CH:10]1[CH2:14][CH2:13][N:12](C(OC(C)(C)C)=O)[CH2:11]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1>C(OCC)(=O)C.C(OCC)C>[CH2:2]([O:9][CH:10]1[CH2:14][CH2:13][NH:12][CH2:11]1)[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1 | CC(C)(C)OC(=O)N1CCC(OCc2ccccc2)C1 | null | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOC(C)=O | CCOCC | null | null | null | null | null | null | null | null | null | null | 0.25 | Hydrogen chloride (4N) in ethyl acetate (1.5 ml) was added to a solution of crude 3-benzyloxy-1-(tert-butoxycarbonyl)-pyrrolidine (705 mg) in diethyl ether (3 ml) and the mixture was stirred for 15 minutes. Reaction was quenched with water, and the solution was washed with diethyl ether. After addition of aqueous sodium hydroxide to make the solution basic, the solution was extracted with diethyl ether and the organic layer was washed with brine and dried over sodium sulfate. Removal of the solvent under reduced pressure afforded 3-benzyloxy-pyrrolidine (182 mg, 37%). | c1ccc(COC2CCNC2)cc1 | null | 40.4 | null |
318,030 | ord_dataset-eb32c2b9cbdf4fc39ce6c9fe0fa11430 | null | 1995-01-01T00:10:00 | true | [F:1][C:2]([F:13])([F:12])[C:3]1[O:4][C:5]([CH3:11])=[C:6]([C:8](=[O:10])[CH3:9])[N:7]=1.[BrH:14].BrBr>C(O)(=O)C>[F:13][C:2]([F:1])([F:12])[C:3]1[O:4][C:5]([CH3:11])=[C:6]([C:8](=[O:10])[CH2:9][Br:14])[N:7]=1 | CC(=O)c1nc(C(F)(F)F)oc1C | Br | null | BrBr | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(=O)O | null | null | null | null | null | null | null | null | null | null | 80 | null | 5.8 g (0.02 mol) of 2-Trifluoromethyl-5-methyl-4-acetyl-oxazole are dissolved in 30 ml of glacial acetic acid, and 3 ml of a 33% strength solution of hydrogen bromide in glacial acetic acid are added. The mixture is heated to 80° C. and, over the course of 1 hour, a solution of 3.2 g (0.02 mol) of bromine in 10 ml of glacial acetic acid is added. After a further 30 minutes the glacial acetic acid is removed. The residue which remains is a dark oil which is reacted further as the crude product. | Cc1oc(C(F)(F)F)nc1C(=O)CBr | null | null | null |
986,327 | ord_dataset-35b56288528641309a040cc2b6710b61 | null | 2010-01-01T00:08:00 | true | [F:1][C:2]([F:48])([F:47])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([O:26][C:27]([F:30])([F:29])[F:28])[CH:23]=[CH:22][C:21]=3[NH:31][C:32]([C@H:34]3[CH2:39][CH2:38][C@H:37]([CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH2:36][CH2:35]3)=[O:33])[C@H:14]2[CH3:46])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[H-].[Na+].I[CH2:52][CH3:53]>>[F:12][C:9]([F:11])([F:10])[C:7]1[CH:6]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([O:26][C:27]([F:30])([F:28])[F:29])[CH:23]=[CH:22][C:21]=3[N:31]([CH2:52][CH3:53])[C:32]([C@H:34]3[CH2:39][CH2:38][C@H:37]([CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH2:36][CH2:35]3)=[O:33])[C@H:14]2[CH3:46])[CH:4]=[C:3]([C:2]([F:1])([F:47])[F:48])[CH:8]=1 | CCOC(=O)C[C@H]1CC[C@H](C(=O)Nc2ccc(OC(F)(F)F)cc2CN2C(=O)O[C@H](c3cc(C(F)(F)F)cc(C(F)(F)F)c3)[C@@H]2C)CC1 | CCI | null | [H-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Ethyl [trans-4-({[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4-(trifluoromethoxy)phenyl]amino}carbonyl)cyclohexyl]acetate (637 mg; 0-913 mmol) was treated with sodium hydride (60% in oil; 40 mg; 1.0 mmol) and iodoethane (110 mL; 1.37 mmol) as described in EXAMPLE 86 to afford ethyl (trans-4-{[[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4-(trifluoromethoxy)phenyl](ethyl)amino]carbonyl}cyclohexyl)acetate as a yellow oil. LCMS=727.0 (M+1)+. 1H NMR (CDCl3, 500 MHz, mixture of atropisomers): δ 7.92 (s, 1 H), 7.80 (s, 1 H), 7.74 (s, 1 U), 7.28-7.22 (m, 1 H), 7.19-7.16 (m, 1 H), 7.14-7.11 (m, 1 H), 5.66 (d, J=8.0 Hz, 1 H), 4.92 (d, J=14.9 Hz, 1 H), 4.25 (d, J=16.9 Hz, 1 H), 4.23-4.05 (m, 4 H), 3.54-3.46 (m, 1 H), 3.08-3.00 (m, 1 H), 2.66-2.58 (m, 1 H), 2.22-2.18 (m, 1 H), 2.09-2.06 (m, 1 H), 1.92-1.52 (m, 6 H), 1.26-1.12 (m, 7 H), 0.81-0.66 (m, 4 H). | CCOC(=O)C[C@H]1CC[C@H](C(=O)N(CC)c2ccc(OC(F)(F)F)cc2CN2C(=O)O[C@H](c3cc(C(F)(F)F)cc(C(F)(F)F)c3)[C@@H]2C)CC1 | null | null | null |
419,542 | ord_dataset-94e21e9990034c729ea727e7d2ab0eb0 | null | 1998-01-01T00:12:00 | true | [I:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4](O)=[O:5].C(Cl)(=O)C([Cl:14])=O>CN(C=O)C.C(Cl)Cl>[I:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([Cl:14])=[O:5] | O=C(O)c1ccccc1I | O=C(Cl)C(=O)Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | null | 2-Iodobenzoic acid (65.92 g, 0.266 mol), oxalyl chloride (40.5 g, 0.319 mol), CH2Cl2 (200 mL) and DMF (10 drops) were stirred at RT overnight. The reaction solution was concentrated, toluene was added and the solution concentrated to afford the crude 2-iodobenzoyl chloride. | O=C(Cl)c1ccccc1I | null | null | null |
1,653,875 | ord_dataset-42cd9bc5aae3485f9a58f1527bd3abf0 | null | 2015-01-01T00:11:00 | true | F[C:2]1[C:9]([F:10])=[CH:8][C:7]([N+:11]([O-:13])=[O:12])=[CH:6][C:3]=1[CH:4]=[O:5].[CH3:14][CH:15]([SH:17])[CH3:16]>CN(C=O)C.CCOC(C)=O>[F:10][C:9]1[C:2]([S:17][CH:15]([CH3:16])[CH3:14])=[C:3]([CH:6]=[C:7]([N+:11]([O-:13])=[O:12])[CH:8]=1)[CH:4]=[O:5] | CC(C)S | O=Cc1cc([N+](=O)[O-])cc(F)c1F | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOC(C)=O | CN(C)C=O | null | null | null | null | null | null | null | null | null | 25 | 1 | To a solution of 11A (51 mg, 0.273 mmol) in DMF (1 mL), were added TEA (0.057 mL, 0.409 mmol) and propane-2-thiol (0.030 mL, 0.327 mmol). The mixture was stirred at rt for 1 h, then was diluted with EtOAc. The organic phase was washed with H2O (2×), 10% LiCl and brine, dried (Na2SO4), filtered though a 1″ pad of SiO2 and concentrated to give 20A (64 mg, 0.263 mmol, 97% yield) as a yellow oil. 1H NMR (400 MHz, chloroform-d) δ ppm 10.69 (1H, s), 8.57 (1H, dd, J=2.4, 1.1 Hz), 8.15 (1H, dd, J=8.5, 2.5 Hz), 3.72 (1H, dt, J=13.4, 6.7 Hz), 1.33 (6H, d, J=6.0 Hz). | CC(C)Sc1c(F)cc([N+](=O)[O-])cc1C=O | null | 96.3 | null |
1,509,238 | ord_dataset-1a1aa5d1c3224edca0aec6e3398da985 | null | 2014-01-01T00:11:00 | true | [NH2:1][C:2]1[C:7]([C@H:8]2[CH2:13][CH2:12][CH2:11][CH2:10][C@@H:9]2[O:14][C:15]2[C:20]([F:21])=[CH:19][C:18]([S:22]([N:25](CC3C=CC(OC)=CC=3OC)[C:26]3[CH:31]=[CH:30][N:29]=[CH:28][N:27]=3)(=[O:24])=[O:23])=[C:17]([F:43])[CH:16]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>ClCCl>[NH2:1][C:2]1[C:7]([C@H:8]2[CH2:13][CH2:12][CH2:11][CH2:10][C@@H:9]2[O:14][C:15]2[C:20]([F:21])=[CH:19][C:18]([S:22]([NH:25][C:26]3[CH:31]=[CH:30][N:29]=[CH:28][N:27]=3)(=[O:23])=[O:24])=[C:17]([F:43])[CH:16]=2)=[CH:6][CH:5]=[CH:4][N:3]=1 | COc1ccc(CN(c2ccncn2)S(=O)(=O)c2cc(F)c(O[C@H]3CCCC[C@@H]3c3cccnc3N)cc2F)c(OC)c1 | null | null | CC[SiH](CC)CC | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O=C(O)C(F)(F)F | ClCCl | null | null | null | null | null | null | null | null | null | null | null | The reaction and aftertreatment were conducted in the same manner as in Example 1b by using the 4-{[(1S*,2R*)-2-(2-aminopyridin-3-yl)cyclohexyl]oxy}-N-(2,4-dimethoxybenzyl)-2,5-difluoro-N-(pyrimidin-4-yl)benzenesulfonamide (0.06 g, 0.09 mmol) prepared in Example 69c, triethylsilane (0.07 mL), trifluoroacetic acid (0.09 mL) and dichloromethane (0.90 mL), to yield the title compound (34.2 mg, 82%) as a colorless solid. | Nc1ncccc1[C@H]1CCCC[C@@H]1Oc1cc(F)c(S(=O)(=O)Nc2ccncn2)cc1F | null | 82.3 | null |
1,602,715 | ord_dataset-9cecb3a8d3b9494191b28dcefea66af2 | null | 2015-01-01T00:07:00 | true | C[O:2][C:3]([C:5]1[C:6]([C:24]2[CH:29]=[CH:28][C:27]([C:30]([OH:32])=O)=[CH:26][CH:25]=2)=[CH:7][CH:8]=[C:9]([C:11]2[S:12][CH:13]=[C:14]([C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([Cl:23])[CH:17]=3)[N:15]=2)[CH:10]=1)=[O:4].[NH2:33][CH:34]1[CH2:39][CH2:38][N:37]([CH3:40])[CH2:36][CH2:35]1>>[Cl:23][C:18]1[CH:17]=[C:16]([C:14]2[N:15]=[C:11]([C:9]3[CH:10]=[C:5]([C:3]([OH:2])=[O:4])[C:6]([C:24]4[CH:29]=[CH:28][C:27]([C:30](=[O:32])[NH:33][CH:34]5[CH2:39][CH2:38][N:37]([CH3:40])[CH2:36][CH2:35]5)=[CH:26][CH:25]=4)=[CH:7][CH:8]=3)[S:12][CH:13]=2)[CH:21]=[CH:20][C:19]=1[Cl:22] | COC(=O)c1cc(-c2nc(-c3ccc(Cl)c(Cl)c3)cs2)ccc1-c1ccc(C(=O)O)cc1 | CN1CCC(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 | Using the conditions of General Procedure E for Amide Coupling in Parallel Mode, 4-[4-(3,4-dichloro-phenyl)-thiazol-2-yl]-biphenyl-2,4′-dicarboxylic acid 2-methyl ester (which may be prepared as described for Intermediate 8; 100 mg, 0.21 mmol) was reacted with 4-amino-1-methylpiperidine (available from Aldrich Chemical Company, Inc.; 71 mg, 0.62 mmol). The resulting ester was hydrolyzed and the acid was purified using HPLC Purification Conditions B to give 4-[4-(3,4-dichloro-phenyl)-thiazol-2-yl]-4′-(1-methyl-piperidin-4-ylcarbamoyl)-biphenyl-2-carboxylic acid (135 mg, 116%). 1H NMR (400 MHz, DMSO-d6) δ ppm 13.20 (br s, 1H), 8.55 (d, J=7.5 Hz, 1H), 8.49 (s, 1H), 8.40 (d, J=1.8 Hz, 1H), 8.35 (d, J=2.0 Hz, 1H), 8.26 (dd, J=8.2, 1.9 Hz, 1H), 8.10 (dd, J=8.3, 2.0 Hz, 1H), 7.92 (d, J=8.3 Hz, 2H), 7.78 (d, J=8.3 Hz, 1H), 7.58 (d, J=8.0 Hz, 1H), 7.50 (d, J=8.3 Hz, 2H), 4.01-4.10 (m, 1H), 3.45-3.51 (m, 2H), 3.05-3.18 (m, 2H), 2.78-2.81 (m, 2H), 2.54 (s, 3H), 2.02-2.10 (m, 2H). | CN1CCC(NC(=O)c2ccc(-c3ccc(-c4nc(-c5ccc(Cl)c(Cl)c5)cs4)cc3C(=O)O)cc2)CC1 | null | 113.5 | null |
1,702,060 | ord_dataset-54347fcace774f89850681d6dec8009f | null | 2016-01-01T00:03:00 | true | Br[C:2]1[C:10]2[N:9]3[CH2:11][CH2:12][NH:13][C:14](=[O:15])[C:8]3=[CH:7][C:6]=2[C:5]([F:16])=[C:4]([F:17])[CH:3]=1.[F:18][C:19]1[CH:20]=[C:21](B(O)O)[CH:22]=[CH:23][C:24]=1[F:25]>>[F:18][C:19]1[CH:20]=[C:21]([C:2]2[C:10]3[N:9]4[CH2:11][CH2:12][NH:13][C:14](=[O:15])[C:8]4=[CH:7][C:6]=3[C:5]([F:16])=[C:4]([F:17])[CH:3]=2)[CH:22]=[CH:23][C:24]=1[F:25] | OB(O)c1ccc(F)c(F)c1 | O=C1NCCn2c1cc1c(F)c(F)cc(Br)c12 | null | null | null | null | null | null | null | 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, white solid (72 mg, 86%), MS (ISP) m/z=335.3 [(M+H)+], mp 317.5° C., was prepared in accordance with the general method of example 1 from 6-bromo-8,9-difluoro-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one (intermediate 4) (75.3 mg, 0.25 mmol) and commercially available 3,4-difluoro-phenylboronic acid (51.3 mg, 0.325 mmol). | O=C1NCCn2c1cc1c(F)c(F)cc(-c3ccc(F)c(F)c3)c12 | null | null | null |
1,380,332 | ord_dataset-d23f2f15886d4c22b7d7ba5f0e203e81 | null | 2013-01-01T00:12:00 | true | [N+:1]([C:4]1[CH:13]=[CH:12][C:7]2[S:8][CH2:9][CH2:10][NH:11][C:6]=2[CH:5]=1)([O-:3])=[O:2].[Cl:14][CH2:15][C:16](Cl)=[O:17]>C1COCC1.C(OCC)(=O)C>[Cl:14][CH2:15][C:16]([N:11]1[CH2:10][CH2:9][S:8][C:7]2[CH:12]=[CH:13][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][C:6]1=2)=[O:17] | O=C(Cl)CCl | O=[N+]([O-])c1ccc2c(c1)NCCS2 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOC(C)=O | C1CCOC1 | null | null | null | null | null | null | null | null | null | 60 | 0.17 | To a stirred solution of 6-nitro-3,4-dihydro-2H-benzo[b][1,4]thiazine (620 mg, 3.16 mmol) in THF (10 mL) was added 2-chloroacetyl chloride (0.277 mL, 3.48 mmol). The resulting mixture was then stirred at 60° C. for 10 minutes. The mixture was then diluted with ethyl acetate and washed with water (3×), 1:1 water:saturated sodium carbonate, and brine. The organic phase was dried, filtered, and concentrated, giving the desired product (860 mg, 100%). 1H NMR (DMSO-d6) δ 8.36 (d, J=2.1 Hz, 1H), 7.96 (dd, J=8.7, 2.1 Hz, 1H), 7.52 (d, J=8.7 Hz, 1H), 4.63 (s, 2H), 3.99-3.92 (m, 2H), 3.39-3.33 (m, 2H); ESI-MS (m/z, %): 295 (M+Na, 68), 273 (MH+, 100), 197 (43). | O=C(CCl)N1CCSc2ccc([N+](=O)[O-])cc21 | null | 99.8 | null |
436,890 | ord_dataset-a1e9aa99368e4e5da8b1786b1c05521d | null | 1999-01-01T00:08:00 | true | O[CH2:2][CH2:3][CH2:4][C:5]1[CH:6]=[C:7]([CH:14]=[CH:15][CH:16]=1)[O:8][CH2:9][C:10]([O:12][CH3:13])=[O:11].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Br:36]C(Br)(Br)Br>C(Cl)Cl>[Br:36][CH2:2][CH2:3][CH2:4][C:5]1[CH:6]=[C:7]([CH:14]=[CH:15][CH:16]=1)[O:8][CH2:9][C:10]([O:12][CH3:13])=[O:11] | COC(=O)COc1cccc(CCCO)c1 | BrC(Br)(Br)Br | null | c1ccc(P(c2ccccc2)c2ccccc2)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | null | null | To a stirred solution of methyl 3-(3-hydroxypropyl)phenoxyacetate (2.00 g) in methylene chloride (20 ml) were added successively triphenylphosphine (2.81 g) and tetrabromomethane (3.55 g) at room temperature. The mixture was evaporated. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=7:1) to give the title compound (1.69 g) having the following physical data. | COC(=O)COc1cccc(CCCBr)c1 | null | 66 | null |
413,139 | ord_dataset-275344fd078b4340b89ca0b6e92beb95 | null | 1998-01-01T00:10:00 | true | [S:1]1[CH:5]=[CH:4][C:3]([SH:6])=[CH:2]1.[CH2:7]([C:11]1([CH2:14][CH3:15])[CH2:13][NH:12]1)[CH2:8][CH2:9][CH3:10]>>[NH2:12][C:11]([CH2:14][CH3:15])([CH2:7][CH2:8][CH2:9][CH3:10])[CH2:13][S:6][C:3]1[CH:4]=[CH:5][S:1][CH:2]=1 | CCCCC1(CC)CN1 | Sc1ccsc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | 25 | 15 | To a solution of n-butyl lithium in hexane (194 ml 1.6M) under nitrogen at -78° C. was added diethyl ether(120 ml) and then dropwise 3-bromothiophene (28 ml). The reaction was warmed to -30° C. and then cooled to -50° C. and powdered sulfur (10 g) was added. The reaction was stirred 15 hours at room temperature and then a solution of potassium hydroxide (24 g) in 160 ml water was added and the ether layer was discarded. The aqueous layer was treated at -5° C. with 6N hydrochloric acid (125 ml) and extracted with dichloromethane and the extract was dried over magnesium sulfate. Filtration and solvent removal afforded crude 3-thiophenthiol (14.1 g). The crude 3-thiophenthiol (10 g) was combined with 2-butyl-2-ethylaziridine (12.6 g, Synthetic Example 1(f)) at 0° C. and the reaction was stirred 15 hours at room temperature. The crude reaction product was purified by column chromatography on silica using 5% methanol in diethyl ether as eluant to give the desired product as an oil (16.4 g). 1H NMR is consistent with proposed structure. | CCCCC(N)(CC)CSc1ccsc1 | null | 78.3 | null |
683,829 | ord_dataset-359b8fc87f4244be89d6f02bc5036eac | null | 2005-01-01T00:09:00 | true | Cl[C:2]1[C:14]2[C:13](=[O:15])[C:12]3[CH:11]=[N:10][CH:9]=[CH:8][C:7]=3[C:6]=2[C:5]2[CH:16]=[CH:17][C:18]([O:20][CH3:21])=[CH:19][C:4]=2[N:3]=1.[NH2:22][CH2:23][CH2:24][N:25]([CH3:34])[CH2:26][CH2:27][CH2:28][N:29]([CH2:31][CH2:32][NH2:33])[CH3:30]>ClCCl>[NH2:33][CH2:32][CH2:31][N:29]([CH3:30])[CH2:28][CH2:27][CH2:26][N:25]([CH3:34])[CH2:24][CH2:23][NH:22][C:2]1[C:14]2[C:13](=[O:15])[C:12]3[CH:11]=[N:10][CH:9]=[CH:8][C:7]=3[C:6]=2[C:5]2[CH:16]=[CH:17][C:18]([O:20][CH3:21])=[CH:19][C:4]=2[N:3]=1 | COc1ccc2c3c(c(Cl)nc2c1)C(=O)c1cnccc1-3 | CN(CCN)CCCN(C)CCN | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | 50 | 4 | A mixture of 6-chloro-3-methoxy-5,9-diaza-benzo[c]fluoren-7-one (50.8 mg) (the compound of Reference Example 1c-2) and N,N′-bis-(2-amino-ethyl)-N,N′-dimethyl-propane-1,3-diamine (0.5 ml) was stirred at 50° C. for 4 hours. The reaction mixture was diluted with dichloromethane. The solution was washed with saturated NaHCO3 solution and dried over magnesium sulfate. The organic layer was evaporated to dryness. The residue was purified by silica gel column chromatography developed by dichloromethane-methanol-ammonia water (25%)=90:10:1. The desired product (49 mg) was obtained as a reddish oil. | COc1ccc2c3c(c(NCCN(C)CCCN(C)CCN)nc2c1)C(=O)c1cnccc1-3 | null | null | null |
941,855 | ord_dataset-ed680843f6d14f5c9901869b2a06b4a4 | null | 2010-01-01T00:03:00 | true | CC(OC(/N=N/C(OC(C)C)=O)=O)C.[OH:15][CH:16]1[CH2:33][CH:32]2[CH:18]([C:19](=[O:45])[N:20]([CH3:44])[CH2:21][CH2:22][CH2:23][CH2:24][CH:25]=[CH:26][CH:27]3[C:29]([C:35]([NH:37][S:38]([CH:41]4[CH2:43][CH2:42]4)(=[O:40])=[O:39])=[O:36])([NH:30][C:31]2=[O:34])[CH2:28]3)[CH2:17]1.[CH:46]([C:49]1[N:50]=[C:51]([C:54]2[CH:63]=[C:62](O)[C:61]3[C:56](=[CH:57][C:58]([O:65][CH3:66])=[CH:59][CH:60]=3)[N:55]=2)[S:52][CH:53]=1)([CH3:48])[CH3:47].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C1COCC1>[CH:46]([C:49]1[N:50]=[C:51]([C:54]2[CH:63]=[C:62]([O:15][CH:16]3[CH2:33][CH:32]4[CH:18]([C:19](=[O:45])[N:20]([CH3:44])[CH2:21][CH2:22][CH2:23][CH2:24][CH:25]=[CH:26][CH:27]5[C:29]([C:35]([NH:37][S:38]([CH:41]6[CH2:42][CH2:43]6)(=[O:40])=[O:39])=[O:36])([NH:30][C:31]4=[O:34])[CH2:28]5)[CH2:17]3)[C:61]3[C:56](=[CH:57][C:58]([O:65][CH3:66])=[CH:59][CH:60]=3)[N:55]=2)[S:52][CH:53]=1)([CH3:48])[CH3:47] | COc1ccc2c(O)cc(-c3nc(C(C)C)cs3)nc2c1 | CN1CCCCC=CC2CC2(C(=O)NS(=O)(=O)C2CC2)NC(=O)C2CC(O)CC2C1=O | null | CC(C)OC(=O)/N=N/C(=O)OC(C)C | c1ccc(P(c2ccccc2)c2ccccc2)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | 25 | 8 | DIAD (22 uL, 0.11 mmol) was added to a mixture of the metathesis product 103 (23 mg), 2-(4-isopropyl-1,3-thiazol-2-yl)-7-methoxyquinolin-4-ol (24 mg, 0.08 mmol), and PPh3 (30 mg, 0.11 mmol) in 1 mL dry THF, in an ice bath. The mixture was stirred at rt overnight and then evaporated. The residue (1.2 mL of a 1.5-mL MeCN solution) was purified by prep-HPLC (Hypercarb 7 uL 100×21.2 mm, 40% to 99% aqueous MeCN in 10 min) to give 3.18 mg MV062308 as cream solids (13% yield). | COc1ccc2c(OC3CC4C(=O)NC5(C(=O)NS(=O)(=O)C6CC6)CC5C=CCCCCN(C)C(=O)C4C3)cc(-c3nc(C(C)C)cs3)nc2c1 | null | 13 | null |
711,059 | ord_dataset-c8069773c1a148aca8ab417108daacc5 | null | 2006-01-01T00:05:00 | true | [CH2:1]([O:8][C@H:9]1[C@@:13]([CH2:16][O:17][C:18]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)([C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=2)[C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)([CH2:14][OH:15])[O:12][C@@H:11]([N:41]2[CH:49]=[C:47]([CH3:48])[C:45](=[O:46])[NH:44][C:42]2=[O:43])[C@@H:10]1[OH:50])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:51]1([CH3:61])[CH:56]=[CH:55][C:54]([S:57](Cl)(=[O:59])=[O:58])=[CH:53][CH:52]=1>N1C=CC=CC=1.CN(C1C=CN=CC=1)C>[CH2:1]([O:8][C@H:9]1[C@@:13]([CH2:16][O:17][C:18]([C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)([C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=2)[C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)([CH2:14][O:15][S:57]([C:54]2[CH:55]=[CH:56][C:51]([CH3:61])=[CH:52][CH:53]=2)(=[O:59])=[O:58])[O:12][C@@H:11]([N:41]2[CH:49]=[C:47]([CH3:48])[C:45](=[O:46])[NH:44][C:42]2=[O:43])[C@@H:10]1[O:50][S:57]([C:54]1[CH:55]=[CH:56][C:51]([CH3:61])=[CH:52][CH:53]=1)(=[O:59])=[O:58])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1 | COc1ccc(C(OC[C@]2(CO)O[C@@H](n3cc(C)c(=O)[nH]c3=O)[C@H](O)[C@H]2OCc2ccccc2)(c2ccccc2)c2ccc(OC)cc2)cc1 | Cc1ccc(S(=O)(=O)Cl)cc1 | null | CN(C)c1ccncc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | c1ccncc1 | null | null | null | null | null | null | null | null | null | null | 25 | 24 | To a solution of nucleoside 6 (2.79 g, 3.9 mmol) in anhydrous pyridine (50 cm3) was added a catalytic amount of 4-(N,N-dimethylamino)pyridine and p-toluenesulphonyl chloride (6.50 g, 34 mmol). The mixture was stirred in the dark for 24 h at room temperature under nitrogen. The reaction was quenched by addition of a saturated aqueous solution of sodium hydrogen carbonate (100 cm3) and the resulting mixture was extracted with dichloromethane. The combined organic phase was washed with saturated aqueous solutions of sodium hydrogen carbonate (3×75 cm3) and sodium chloride (2×75 cm3). The separated organic phase was dried (Na2SO4) and evaporated to dryness under reduced pressure. The residue was purified by silica gel column chromatography using dichloromethane/methanol/pyridine (0.5% methanol; 0.5% pyridine, v/v) as eluent to afford nucteoside 7 (2.40 g, 62%) as a yellowish foam after evaporation of the solvents. δC ((CD3)2SO) 163.2 (C-4), 158.2, 145.9, 145.1, 144.3, 136.8, 135.0, 134.9, 134.8, 131.8, 131.6, 130.2, 130.0, 129.7, 128.2, 127.9, 127.8, 127.6, 127.5, 127.5, 127.4, 126.8, 113.3 (DMT, C-6, 2×Ts, benzyl), 150.2 (C-2), 110.8 (C-5), 95.0, 86.2 (DMT, C-4′), 82.2, 81.9 (C-1′, C-2′), 81.2 (C-3′), 72.9 (CH2Ph), 79 (C-5″), 64 (C-5′), 55.1 (2×CH3O), 21.2, 21.2 (2×CH3), 12.0 (5-CH3). | COc1ccc(C(OC[C@]2(COS(=O)(=O)c3ccc(C)cc3)O[C@@H](n3cc(C)c(=O)[nH]c3=O)[C@H](OS(=O)(=O)c3ccc(C)cc3)[C@H]2OCc2ccccc2)(c2ccccc2)c2ccc(OC)cc2)cc1 | null | 62.2 | null |
257,128 | ord_dataset-30ad5cf6083a45a387b45bebad1a4d65 | null | 1992-01-01T00:10:00 | true | [O:1]=[C:2]1[C:6]([CH2:7][S:8][C:9]2[CH2:10][S:11][C@@H:12]3[C@H:32]([NH:33]C(=O)CC4C=CC=CC=4)[C:31](=[O:43])[N:13]3[C:14]=2[C:15]([O:17][CH:18]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:16])=[CH:5][CH2:4][O:3]1.CN1CCOCC1>ClCCl>[NH2:33][C@@H:32]1[C:31](=[O:43])[N:13]2[C:14]([C:15]([O:17][CH:18]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[O:16])=[C:9]([S:8][CH2:7][C:6]3[C:2](=[O:1])[O:3][CH2:4][CH:5]=3)[CH2:10][S:11][C@H:12]12 | O=C(Cc1ccccc1)N[C@@H]1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(SCC3=CCOC3=O)CS[C@H]12 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | CN1CCOCC1 | null | null | null | null | null | null | null | null | null | -30 | 0.5 | Diphenylmethyl 3-(2,5-dihydro-2-oxofuran-3-yl-methylthio)-7β-phenylacetamidoceph-3-em-4-carboxylate (0.83g) was dissolved in dichloromethane (11 ml) and treated with N-methylmorpholine (298μl). The atmosphere was purged with argon and the mixture cooled to -30° C. A solution of phosphorus pentachloride in dichloromethane (10.6 ml of 40 mg ml-1 solution) was added and the reaction stirred at approximately -20° C. for 30 min. Methanol (2.7 ml) was added and the reaction allowed to warm to room temperature. Water (3.6 ml) was then added and the mixture stirred vigorously for 45 min. Dichloromethane was removed using a rotary evaporator and the residue partitioned between ethyl acetate and water. The pH of the solution was adjusted to 6.0 with 1.0M aqueous ammonia before separating the organic phase, washing with water and brine, and finally drying over magnesium sulphate. Evaporation of solvent gave a residue which was purified by chromatography on silica gel (Keiselgel, 7:3 ethyl acetate:hexane) to give the title compound (600 mg). υmax (CH2Cl2) 1780 and 1760cmhu -1; δH (CDCl3) 2.04 (2H, bs) 3.44-3.73 (4H, m), 4.70 (2H, s), 4.77 (1H, d, J 5.0Hz), 4.96 (1H, d, J 4.9Hz), 6.96 (1H, s) 7.11 (1H, s), 7.27-7.46 (10H, m). [mass spectrum: +ve ion (Thioglycerol) MH+ 495]. | N[C@@H]1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(SCC3=CCOC3=O)CS[C@H]12 | null | 89.6 | null |
1,605,178 | ord_dataset-9cecb3a8d3b9494191b28dcefea66af2 | null | 2015-01-01T00:07:00 | true | C([Li])(C)(C)C.Br[C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[NH:12][N:11]=[C:10]2[CH3:16].CN(C)[CH:19]=[O:20]>CCCCC.C1COCC1>[CH3:16][C:10]1[C:9]2[C:13](=[CH:14][CH:15]=[C:7]([CH:19]=[O:20])[CH:8]=2)[NH:12][N:11]=1 | CN(C)C=O | Cc1n[nH]c2ccc(Br)cc12 | null | [Li]C(C)(C)C | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | CCCCC | null | null | null | null | null | null | null | null | null | null | 0.25 | Tetrahydrofuran (600 ml) was cooled down to −78° C. under argon atmosphere. At this temperature, a 1.7 M solution of tert-butyllithium in n-pentane (200 ml) was added dropwise. After 15 minutes at −78° C., a solution of 22.4 g (106.1 mmol) 5-bromo-3-methyl-1H-indazole in THF (300 ml) was added dropwise at such a rate that the temperature of the solution did not exceed −70° C. The mixture was stirred for 30 minutes before N,N-dimethylformamide (24.5 ml) was added dropwise. After 20 min, the cooling bath was removed, and stirring was continued for 1 h before water (250 ml) was added carefully. The mixture was extracted several times with ethyl acetate (500 ml). The combined organic layers were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, and concentrated under reduced pressure to yield 18.5 g of crude 3-methyl-1H-indazole-5-carbaldehyde, which was used in the next step without further purification. | Cc1n[nH]c2ccc(C=O)cc12 | null | null | null |
886,561 | ord_dataset-d728a2f811c0424cbcdb5a84d02b93ae | null | 2009-01-01T00:06:00 | true | [F:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][C:3]=1[OH:10].C(N(CC)C(C)C)(C)C.Cl[CH2:21][O:22][CH3:23].Cl>ClCCl>[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][C:3]=1[O:10][CH2:21][O:22][CH3:23] | COCCl | O=Cc1ccc(F)c(O)c1 | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(C(C)C)C(C)C | ClCCl | null | null | null | null | null | null | null | null | null | 25 | 3 | 4-Fluoro-3-hydroxybenzaldehyde (11.9 g) and N,N-diisopropylethylamine (44 mL) were dissolved in dichloromethane (100 mL). To the mixture was added chloromethylmethylether (13 mL), and the mixture was stirred at room temperature for 3 hours. To the reaction mixture was added dropwise 1 mol/L hydrochloric acid (250 mL), and the resulting mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to give the title compound (14.5 g). | COCOc1cc(C=O)ccc1F | null | null | null |
1,322,185 | ord_dataset-cfad8b3f00044bcda60a96b019f09872 | null | 2013-01-01T00:08:00 | true | [CH3:1][O:2][C:3](=[O:15])[CH2:4][NH:5][C:6]([C:8]1[CH:13]=[CH:12][N:11]=[CH:10][C:9]=1[NH2:14])=[O:7].[C:16](N1C=CN=C1)(N1C=CN=C1)=[O:17].N12CCCN=C1CCCCC2>O1CCCC1>[CH3:1][O:2][C:3](=[O:15])[CH2:4][N:5]1[C:6](=[O:7])[C:8]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[NH:14][C:16]1=[O:17] | COC(=O)CNC(=O)c1ccncc1N | O=C(n1ccnc1)n1ccnc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | C1CCC2=NCCCN2CC1 | null | null | null | null | null | null | null | null | null | null | 2 | To a solution of 100 mg of [(3-amino-pyridine-4-carbonyl)-amino]-acetic acid methyl ester in tetrahydrofuran (4.5 mL) is added 194 mg of 1,1′-carbonyldiimidazole and 0.18 mL of 1,8-diazabicyclo[5.4.0]undec-7-ene at room temperature and the mixture is stirred at the same temperature for 2 h. Then the solvent is removed under vacuum and the residue is purified by flash chromatography on silica gel to give 100 mg (89%) of (2,4-dioxo-1,4-dihydro-2H-pyrido[3,4-d]pyrimidin-3-yl)-acetic acid methyl ester. | COC(=O)Cn1c(=O)[nH]c2cnccc2c1=O | null | 88.9 | null |
1,605,348 | ord_dataset-9cecb3a8d3b9494191b28dcefea66af2 | null | 2015-01-01T00:07:00 | true | [Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4](F)[N:3]=1.[C:9]1([C@@H:15]([NH2:17])[CH3:16])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>C(OCC)(=O)C>[Br:1][C:2]1[N:3]=[C:4]([NH:17][C@H:15]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH3:16])[CH:5]=[CH:6][CH:7]=1 | C[C@H](N)c1ccccc1 | Fc1cccc(Br)n1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOC(C)=O | null | null | null | null | null | null | null | null | null | null | 100 | null | A mixture of 2-bromo-6-fluoropyridine (500 mg, 2.84 mmol) and (S)-(−)-1-phenylethylamine (0.435 mL, 3.41 mmol) were heated at 100° C. for 12 hours. The mixture was cooled to room temperature, dissolved in ethyl acetate, washed with water and brine, dried over anhydrous sodium sulfate, filtered, and concentrated. Purification by column chromatography (silica gel, 6% ethyl acetate-hexane) afforded the title compound. | C[C@H](Nc1cccc(Br)n1)c1ccccc1 | null | null | null |
1,240,680 | ord_dataset-c544c0c663f54dbea4ddb52ddde7934e | null | 2013-01-01T00:01:00 | true | [F:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[C:4]([O:10][CH3:11])[CH:3]=1.P(Cl)(Cl)(Cl)=O.CN([CH:20]=[O:21])C>>[F:1][C:2]1[CH:3]=[C:4]([O:10][CH3:11])[CH:5]=[C:6]([O:8][CH3:9])[C:7]=1[CH:20]=[O:21] | COc1cc(F)cc(OC)c1 | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O=P(Cl)(Cl)Cl | null | null | null | null | null | null | null | null | null | null | 25 | 8 | To a solution of 1-fluoro-3,5-dimethoxybenzene (3.12 g, 20.0 mmol) in DMF (15 mL) was added dropwise phosphoryl trichloride (1.55 mL) at 0° C. The reaction mixture was stirred at room temperature overnight and poured onto ice. The resulting mixture was extracted with ethyl acetate (2×50 mL) and the combined organic layers were dried over anhydrous Na2SO4, concentrated in vacuo. The residue was purified by column chromatography on silica gel (EtOAc/PE=1/8) to give the title compound as a yellow solid (2.75 g, Yield: 74.6%). 1H NMR (400 MHz, DMSO-d) δ 10.15 (s, 1H), 6.52-6.56 (m, 2H), 3.91 (s, 3H), 3.88 (s, 3H). MS (ESI) m/z=185 [M+H]+. | COc1cc(F)c(C=O)c(OC)c1 | null | 74.6 | null |
386,610 | ord_dataset-d330662edaed408d950898172aba7a4c | null | 1997-01-01T00:12:00 | true | [NH2:1][C:2]1[CH:3]=[C:4]([CH:11](O)[CH2:12][CH2:13][N:14]([CH3:16])[CH3:15])[C:5]2[O:9][CH2:8][CH2:7][C:6]=2[CH:10]=1>FC(F)(F)C(O)=O>[CH3:16][N:14]([CH3:15])[CH2:13][CH:12]=[CH:11][C:4]1[C:5]2[O:9][CH2:8][CH2:7][C:6]=2[CH:10]=[C:2]([NH2:1])[CH:3]=1 | CN(C)CCC(O)c1cc(N)cc2c1OCC2 | 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 | A solution of 1-(5-amino-2,3-dihydrobenzofuran-7-yl)-3-dimethylaminopropan-1-ol (D 16) (2.12 g) in trifluoroacetic acid (60 ml) was refluxed for 10h, cooled and the solvent evaporated under reduced pressure. The residue was partitioned between 10% Na2CO3 and ethyl acetate, the organic phase was dried (Na2SO4) and the solvent evaporated under reduced pressure, to give the title compound as an orange foam (2.07 g, quantitative). | CN(C)CC=Cc1cc(N)cc2c1OCC2 | null | 105.7 | null |
1,592,717 | ord_dataset-e8c6a25568b64529b960953990e6921f | null | 2015-01-01T00:06:00 | true | [C:1](Cl)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:10]1([CH:16]([NH:19][C:20]([C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][CH:30]=2)[NH:27][CH:26]=[CH:25]3)=[O:21])[CH2:17][CH3:18])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.CCN(CC)CC>C(Cl)Cl>[C:1]([N:27]1[C:28]2[C:24](=[CH:23][C:22]([C:20]([NH:19][CH:16]([C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH2:17][CH3:18])=[O:21])=[CH:30][CH:29]=2)[CH:25]=[CH:26]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1 | O=C(Cl)c1ccccc1 | CCC(NC(=O)c1ccc2[nH]ccc2c1)c1ccccc1 | 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 | null | Benzoyl chloride (1.1 equiv) was added to a solution of N-(1-phenylpropyl)-1H-indole-5-carboxamide in CH2Cl2, Et3N (1.3 equiv) at room temperature. After the reaction was completed, the solvent was evaporated and the residual was purified by silica gel column chromatography to get the product. LC-MS 383 (M+H). | CCC(NC(=O)c1ccc2c(ccn2C(=O)c2ccccc2)c1)c1ccccc1 | null | null | null |
1,697,663 | ord_dataset-54347fcace774f89850681d6dec8009f | null | 2016-01-01T00:03:00 | true | [CH3:1][O:2][N:3]([CH3:16])[C:4](=[O:15])[C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([CH3:11])[C:6]=1[N+:12]([O-:14])=[O:13].C1C(=O)N([Br:24])C(=O)C1.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl>[Br:24][CH2:11][C:7]1[C:6]([N+:12]([O-:14])=[O:13])=[C:5]([CH:10]=[CH:9][CH:8]=1)[C:4]([N:3]([O:2][CH3:1])[CH3:16])=[O:15] | CON(C)C(=O)c1cccc(C)c1[N+](=O)[O-] | O=C1CCC(=O)N1Br | null | O=C(OOC(=O)c1ccccc1)c1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClC(Cl)(Cl)Cl | null | null | null | null | null | null | null | null | null | null | 80 | null | A mixture of Intermediate 37A (5.5 g, 24.53 mmol), NBS (5.24 g, 29.4 mmol) and benzoyl peroxide (0.594 g, 2.453 mmol) in CCl4 (80 mL) was purged with nitrogen and then heated to 80° C. for 4.5 h. The reaction mixture was cooled to room temperature and then quenched with water. The mixture was extracted with DCM and the combined extracts were washed with saturated NaHCO3 and brine and then dried (Na2SO4), filtered and concentrated to dryness. The crude material was purified by flash chromatography (SiO2, 80 g column, EtOAc/hexane=0-100%) to afford Intermediate 37B. | CON(C)C(=O)c1cccc(CBr)c1[N+](=O)[O-] | null | null | null |
1,033,842 | ord_dataset-83acb82dc5ba4f7aba439b9875aaac43 | null | 2011-01-01T00:02:00 | true | [C:1]([C:3]1([NH:6][C:7]([C@@H:9]2[CH2:13][C@@H:12]([S:14]([C:17]3[CH:22]=[CH:21][C:20](F)=[CH:19][C:18]=3[C:24]([F:27])([F:26])[F:25])(=[O:16])=[O:15])[CH2:11][C@H:10]2[C:28]([N:30]2[CH2:33][C:32]([F:35])([F:34])[CH2:31]2)=[O:29])=[O:8])[CH2:5][CH2:4]1)#[N:2].Cl.[F:37][C:38]1([F:43])[CH2:42][CH2:41][NH:40][CH2:39]1>>[C:1]([C:3]1([NH:6][C:7]([CH:9]2[CH2:13][CH:12]([S:14]([C:17]3[CH:22]=[CH:21][C:20]([N:40]4[CH2:41][CH2:42][C:38]([F:43])([F:37])[CH2:39]4)=[CH:19][C:18]=3[C:24]([F:25])([F:26])[F:27])(=[O:15])=[O:16])[CH2:11][CH:10]2[C:28]([N:30]2[CH2:33][C:32]([F:35])([F:34])[CH2:31]2)=[O:29])=[O:8])[CH2:5][CH2:4]1)#[N:2] | FC1(F)CCNC1 | N#CC1(NC(=O)[C@@H]2C[C@@H](S(=O)(=O)c3ccc(F)cc3C(F)(F)F)C[C@H]2C(=O)N2CC(F)(F)C2)CC1 | 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 title compound was prepared in analogy to Example 127 using (1R,2R,4R)-2-(3,3-Difluoro-azetidine-1-carbonyl)-4-(4-fluoro-2-trifluoromethyl-benzenesulfonyl)-cyclopentanecarboxylic acid (1-cyano-cyclopropyl)-amide (Example 118) and 3,3-difluoropyrrolidine hydrochloride. Off-white solid. MS (EI): 611.2 (M+H)+. | N#CC1(NC(=O)C2CC(S(=O)(=O)c3ccc(N4CCC(F)(F)C4)cc3C(F)(F)F)CC2C(=O)N2CC(F)(F)C2)CC1 | null | null | null |
1,583,706 | ord_dataset-380e279f82154dba9e08ab51b3bdd08a | null | 2015-01-01T00:05:00 | true | [CH3:1][C:2]1[NH:3][C:4]2[N:5]([N:14]=[C:15]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH:16]=2)[C:6](=O)[C:7]=1[CH2:8][C:9]([O:11][CH3:12])=[O:10].O=P(Cl)(Cl)[Cl:25]>>[Cl:25][C:6]1[N:5]2[N:14]=[C:15]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH:16]=[C:4]2[N:3]=[C:2]([CH3:1])[C:7]=1[CH2:8][C:9]([O:11][CH3:12])=[O:10] | COC(=O)Cc1c(C)[nH]c2cc(-c3ccccc3)nn2c1=O | O=P(Cl)(Cl)Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | 0 | null | To methyl 2-(5-methyl-7-oxo-2-phenyl-4,7-dihydropyrazolo[1,5-a]pyrimidin-6-yl)acetate (3 g, 10.09 mmol) was added POCl3 (25 mL, 268 mmol). The reaction mixture was heated at reflux for 1 h. After cooling, the reaction mixture was added drop-wise to ice-water. A brown solid precipitated. The solid was filtered and washed with water, then dissolved in ethyl acetate. The organic solution was washed with saturated NaHCO3 and dried over sodium sulfate. The solvent was evaporated to give the title compound (2.77 g, 84%). 1H-NMR (400 MHz, DMSO-d6) δ 2.58 (3H, s), 3.71 (3 H, s), 4.04 (2 H, s), 7.29 (1 H, s), 7.43-7.58 (3 H, m), 8.07 (2 H, d, J=7.0 Hz). | COC(=O)Cc1c(C)nc2cc(-c3ccccc3)nn2c1Cl | null | 86.9 | null |
385,847 | ord_dataset-d330662edaed408d950898172aba7a4c | null | 1997-01-01T00:12:00 | true | [CH3:1][O:2][C:3](=[O:13])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([Cl:11])=[C:7]([Cl:12])[CH:6]=1.Br[CH2:15]CO.Cl>C1COCC1>[Cl:12][C:7]1[CH:6]=[C:5]([CH:4]2[CH2:15][CH2:1][O:2][C:3]2=[O:13])[CH:10]=[CH:9][C:8]=1[Cl:11] | COC(=O)Cc1ccc(Cl)c(Cl)c1 | OCCBr | 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 | 45 | 2.5 | Heat [(CH3)3Si]2NLi (230 ml, 1.0M in THF) under N2 to 45° C. and add 3,4 dichlorophenyl acetic acid methyl ester (40 g, 0.183 moles) dissolved in 60 ml of dry THF dropwise over 2 h. Stir the solution at 45° C. for another 2.5 h. Cool the solution to room temperature, add a dry THF solution (30 ml.) of THP-protected Br(CH2)2OH dropwise over 1 h., and stir the solution for 24 h. Cool the solution in an ice bath and quench the reaction by adding, dropwise, 250 ml. of 1.0M aqueous HCl. Extract the solution with Et2 O, wash the organic layer twice with 1.0M aqueous HCl, then with water, and dry over anhydrous Na2SO4. Remove the solvent, dissolve the residue in CH3OH and add 0.5 g of pTSA. Stir the solution at room temperature overnight, remove the solvent, add CH3OH (500 ml) and stir for 6 h. Remove the solvent again, add more CH3OH (500 ml.), stir overnight and remove the solvent. Dissolve the resulting oil in CH2Cl2 (1200 ml.), wash twice with saturated aqueous NaHCO3, then water, and dry over anhydrous Na2SO4. Remove the solvent in vacuo. Purify the reaction mixture by flash chromatography (SiO2) using EtOAc: hexanes (3:7) as eluent. Yield: 22 g. Cl-MS: 231 (100%), 233 (65%). | O=C1OCCC1c1ccc(Cl)c(Cl)c1 | null | null | null |
139,552 | ord_dataset-7d359d96b3a64882921ebdc6c850e22e | null | 1986-01-01T00:01:00 | true | [C:1]([NH:6][C:7]1[CH2:11][CH2:10][N:9]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=2)[N:8]=1)(=O)[CH2:2][CH2:3][CH3:4].[H-].[Al+3].[Li+].[H-].[H-].[H-]>>[CH2:1]([NH:6][C:7]1[CH2:11][CH2:10][N:9]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:20])([F:21])[F:19])[CH:13]=2)[N:8]=1)[CH2:2][CH2:3][CH3:4] | CCCC(=O)NC1=NN(c2cccc(C(F)(F)F)c2)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 | According to the method of Example 1, 3-butyramido-1-(3-trifluoromethylphenyl)-2-pyrazoline was reduced with lithium aluminium hydride to produce 3-butylamino-1-(3-trifluoromethylphenyl)-2-pyrazoline which was a gum (yield 2.4 g) and was recrystallized as the hydrochloride m.p. 173.4° (yield 1.65 g). | CCCCNC1=NN(c2cccc(C(F)(F)F)c2)CC1 | null | null | null |
226,676 | ord_dataset-67612e25ea9d4b29966a776893a43d59 | null | 1991-01-01T00:04:00 | true | C([N:8]1[C:20]2[C:19]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[N:13]([CH2:21][CH3:22])[C:12](=[O:23])[C:11]=2[N:10]=[CH:9]1)C1C=CC=CC=1>C(O)(=O)C.[C].[Pd]>[CH2:21]([N:13]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:19]=2[C:20]2[NH:8][CH:9]=[N:10][C:11]=2[C:12]1=[O:23])[CH3:22] | CCn1c(=O)c2ncn(Cc3ccccc3)c2c2ccccc21 | null | null | [Pd] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(=O)O | null | null | null | null | null | null | null | null | null | null | 70 | 3 | 3.0 g (0.0099 mol) of Compound e obtained in Reference Example 4 was dissolved in 110 ml of acetic acid. 0.89 g of 10% palladium carbon was added to the solution. Under hydrogen stream, the solution was stirred 3 hours at 70° C. After filtration, the filtrate was concentrated under reduced pressure. Anhydrous sodium carbonate was added to the solution for neutralization, and a precipitate was collected by filtration and recrystallized from isopropanol-water, to afford 2.0 g (yield: 93%) of Compound h. | CCn1c(=O)c2nc[nH]c2c2ccccc21 | null | 94.7 | null |
1,497,355 | ord_dataset-366bdd9ee72d474cbe6f3f9e54dd96d2 | null | 2014-01-01T00:10:00 | true | [C:1]1([NH2:8])[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH2:7].[O:9]([CH2:16][C:17](O)=O)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>Cl>[O:9]([CH2:16][C:17]1[NH:8][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=2[N:7]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1 | O=C(O)COc1ccccc1 | Nc1ccccc1N | 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 | 130 | 18 | A 100 mL flask fitted with a stir-bar and condenser was charged with 1,2-phenylenediamine (9.94 g, 92.1 mmol), phenoxyacetic acid (14.0 g, 92.1 mmol), and 4M HCl (140 mL). The suspension was heated in a 130° C. bath forming a green solution. After 18 hr, the reaction had gone to completion as monitored by HPLC. The mixture was cooled in an ice bath forming a solid. The solid was filtered, pressed with rubber dam, and rinsed with H2O (2×15 mL). The residue was partitioned with EtOAc (300 mL) and saturated NaHCO3 (125 mL). The organic phase was washed with brine (100 mL), filtered through phase separation paper, and concentrated in vacuo to give 18.5 g of 61 as an off-white solid (90%). 1H NMR (300 MHz, CDCl3): δ 10.08 (bs, 1H), 7.82-7.40 (bm, 2H), 7.35-7.26 (m, 4H), 7.08-6.95 (m, 3H), 5.40 (s, 2H) ppm. HPLC analysis (15:10:75 H2O:A1:MeOH) showed a purity of greater than 99% with a retention time of 4.2 min. | c1ccc(OCc2nc3ccccc3[nH]2)cc1 | null | 89.6 | null |
1,717,965 | ord_dataset-3f2a531ffbae4b9eb1048afcd7953beb | null | 2016-01-01T00:04:00 | true | [CH2:1]([O:3][C:4]([C:6]1[S:7][C:8](Br)=[CH:9][CH:10]=1)=[O:5])[CH3:2].C(N(CC)CC)C.[CH3:19][C:20]([CH3:24])([CH3:23])[C:21]#[CH:22]>CN(C=O)C.[Cu](I)I.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:1]([O:3][C:4]([C:6]1[S:7][C:8]([C:22]#[C:21][C:20]([CH3:24])([CH3:23])[CH3:19])=[CH:9][CH:10]=1)=[O:5])[CH3:2] | C#CC(C)(C)C | CCOC(=O)c1ccc(Br)s1 | null | I[Cu]I | [Pd] | O=C(/C=C/c1ccccc1)/C=C/c1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | CCN(CC)CC | null | null | null | null | null | null | null | null | null | null | null | A mixture of 5-bromo-thiophene-2-carboxylic acid ethyl ester (7 g, 30 mmol), copper iodide (1.2 g, 6 mmol), triethylamine (20 mL) in DMF (100 mL) was degassed in a 350 mL pressure bottle. Then tris(dibenzylideneacetone)dipalladium(0) (2.1 g, 3 mmol) and 3,3-dimethyl-but-1-yne (18.3 mL, 150 mmol) were added and heated at 80 degree for 3 hours. The reaction mixture was filtered on celite and washed with ethyl acetate. The solution was diluted with water and extracted twice with ethyl acetate. The organic phases were combined and washed with water. After drying and concentration, the crude residue was purified by flash chromatography to yield 6.9 g (95%) of 5-(3,3-Dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid ethyl ester as a yellow oil. | CCOC(=O)c1ccc(C#CC(C)(C)C)s1 | null | 97.3 | null |
1,681,204 | ord_dataset-3953983e052a4076aa7cc0880b79cb8b | null | 2016-01-01T00:01:00 | true | [C:1]([OH:9])(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1.[NH2:10][CH2:11][CH2:12][S:13][S:14][CH2:15][CH2:16][NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21].CCN=C=NCCCN(C)C>CC#N.CCOC(C)=O>[C:1]([NH:10][CH2:11][CH2:12][S:13][S:14][CH2:15][CH2:16][NH:17][C:18](=[O:24])[O:19][C:20]([CH3:22])([CH3:21])[CH3:23])(=[O:9])[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1 | O=C(O)c1cccnc1 | CC(C)(C)OC(=O)NCCSSCCN | null | CCN=C=NCCCN(C)C | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOC(C)=O | CC#N | null | null | null | null | null | null | null | null | null | 25 | 4 | Separately, nicotinic acid (246 mg, 2.0 mmol) was taken up in CH3CN (10 mL) along with tert-butyl 2-(2-(2-aminoethyl)disulfanyl)ethylcarbamate (503 mg, 2.0 mmol), EDCI (422 mg, 2.2 mmol). The resulting reaction mixture was stirred at room temperature for 4 h and then diluted with EtOAc. The organic layer was washed with dilute aqueous NaHCO3, brine, dried over Na2SO4, filtered and concentrated under reduced pressure. Purification by silica gel chromatography (CH2Cl2) afforded tert-butyl 2-(2-(2-(nicotinamido)ethyl)disulfanyl)ethylcarbamate (400 mg, 56%). | CC(C)(C)OC(=O)NCCSSCCNC(=O)c1cccnc1 | null | 55.9 | null |
818,720 | ord_dataset-50f99930fc41474db226bc80774b38df | null | 2008-01-01T00:04:00 | true | C(OC([C:6]1[S:7][CH:8]=[C:9]2[C:14]=1[NH:13][C:12](=[O:15])[CH:11]=[C:10]2Cl)=O)C.[C:17]([O:21][C:22]([N:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1)=[O:23])([CH3:20])([CH3:19])[CH3:18]>>[CH2:17]([O:21][C:22]([C:11]1[C:12](=[O:15])[NH:13][C:14]2[C:9]([C:10]=1[N:27]1[CH2:28][CH2:29][N:24]([C:22]([O:21][C:17]([CH3:20])([CH3:18])[CH3:19])=[O:23])[CH2:25][CH2:26]1)=[CH:8][S:7][CH:6]=2)=[O:23])[CH3:18] | CCOC(=O)c1scc2c(Cl)cc(=O)[nH]c12 | CC(C)(C)OC(=O)N1CCNCC1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | In another method, intermediate 7-chloro-5-oxo-4,5-dihydro-2-thia-4-aza-indene-3-carboxylic acid ethyl ester, depicted by formula (25), was reacted with tert-butyl-1-piperazine carboxylate to yield 7-(4-tert-butoxycarbonyl-piperazin-1-yl)-5-oxo-4,5-dihydro-2-thia-4-aza-indene-6-carboxylic acid ethyl ester, depicted by formula (28). This intermediate was either reacted with an appropriate halide (R1—X) or boronic acid (R1—B(OH)2) to yield an intermediate of structure (29), which was deprotected and reacted with an appropriate acid chloride (R3—COCl) or acid (R3—COOH) to yield target compounds of structure (II), with R2 as ethyl carboxylate, and R1 and R3 as defined above, as shown in Scheme 14. | CCOC(=O)c1c(N2CCN(C(=O)OC(C)(C)C)CC2)c2cscc2[nH]c1=O | null | null | null |
1,322,902 | ord_dataset-cfad8b3f00044bcda60a96b019f09872 | null | 2013-01-01T00:08:00 | true | Br[C:2]1[S:3][C:4]([C:7]([NH:9][CH2:10][C:11]2[C:20](=[O:21])[C:19]3[C:14](=[CH:15][C:16]([Cl:22])=[CH:17][CH:18]=3)[N:13]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH:12]=2)=[O:8])=[CH:5][N:6]=1.[NH:29]1[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1>CN1C(=O)CCC1>[Cl:22][C:16]1[CH:15]=[C:14]2[C:19]([C:20](=[O:21])[C:11]([CH2:10][NH:9][C:7]([C:4]3[S:3][C:2]([N:29]4[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]4)=[N:6][CH:5]=3)=[O:8])=[CH:12][N:13]2[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[CH:18][CH:17]=1 | O=C(NCc1cn(-c2ccccc2)c2cc(Cl)ccc2c1=O)c1cnc(Br)s1 | C1CCNCC1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN1CCCC1=O | null | null | null | null | null | null | null | null | null | null | 120 | null | A mixture of 2-bromo-N-((7-chloro-4-oxo-1-phenyl-1,4-dihydroquinolin-3-yl)methyl)-thiazole-5-carboxamide (intermediate F) (30 mg, 0.063 mmol) and piperidine (10.8 mg, 0.126 mmol) in NMP was heated to 120° C. in a sealed microwave tube. After heating for 2 hr., the mixture was allowed to cool to room temperature. The crude product was purified using preparative reverse-phase HPLC, providing 2-piperidin-1-yl-thiazole-5-carboxylic acid (7-chloro-4-oxo-1-phenyl-1,4-dihydro-quinolin-3-ylmethyl)-amide. MS calcd. for C25H23ClN4O2S [(M+H)+] 479.1, obsd. 478. | O=C(NCc1cn(-c2ccccc2)c2cc(Cl)ccc2c1=O)c1cnc(N2CCCCC2)s1 | null | null | null |
474,331 | ord_dataset-d56f0a7ec215495c92e641d9fa932d28 | null | 2000-01-01T00:09:00 | true | [F:1][C:2]([F:22])([F:21])[C:3]1[CH:4]=[C:5]2[C:14](=[CH:15][CH:16]=1)[CH:13]=[C:12]1[C:7]([C:8]([C:17]([O:19]C)=[O:18])=[CH:9][CH:10]=[CH:11]1)=[N:6]2>CO.O>[F:22][C:2]([F:1])([F:21])[C:3]1[CH:4]=[C:5]2[C:14](=[CH:15][CH:16]=1)[CH:13]=[C:12]1[C:7]([C:8]([C:17]([OH:19])=[O:18])=[CH:9][CH:10]=[CH:11]1)=[N:6]2 | COC(=O)c1cccc2cc3ccc(C(F)(F)F)cc3nc12 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CO | null | null | null | null | null | null | null | null | null | null | null | Cyclization of this as above, followed by immediate hydrolysis of the crude methyl 6-trifluoromethylacridine-4-carboxylate, gave 6-trifluoromethylacridine-4-carboxylic acid (81%), mp (MeOH/H2O) 244-246° C. 1H NMR [(CD3)2SO] δ 7.93 (t, J=7.9 Hz, 1 H, H-3), 7.98 (dd, J=8.9, 1.5 Hz, 1 H, ArH), 8.56 (d, J=8.8 Hz, 1 H, ArH), 8.60 (d, J=8.5 Hz, 1 H, ArH), 8.79 (dd, J=7.0, 1.1 Hz, 1 H, ArH), 8.86 (s, 1 H, H-5), 9.66 (s, 1 H, H-9). | O=C(O)c1cccc2cc3ccc(C(F)(F)F)cc3nc12 | null | 81 | null |
900,149 | ord_dataset-de6bce51790e4004a27e1a8f2bcc7ded | null | 2009-01-01T00:08:00 | true | [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[CH:6]2.[NH:12]1[CH2:17][CH2:16][C:15](O)(O)[CH2:14][CH2:13]1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[C:6]2[C:15]1[CH2:16][CH2:17][NH:12][CH2:13][CH:14]=1 | OC1(O)CCNCC1 | COc1ccc2[nH]ccc2c1 | null | null | null | null | null | null | null | 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 experimental protocol used is described in the literature (Eur. J. Med. Chem. (1987) 22, 33-43), starting from 5-methoxy-1H-indole and 4,4-piperidinediol. | COc1ccc2[nH]cc(C3=CCNCC3)c2c1 | null | null | null |
262,576 | ord_dataset-ddb1b60bec5c45e9a2938b6dac04376c | null | 1993-01-01T00:02:00 | true | S(Cl)([Cl:3])=O.[F:5][C:6]1[CH:22]=[CH:21][C:9]([C:10]([C:12]2[CH:20]=[CH:19][CH:18]=[CH:17][C:13]=2[C:14](O)=[O:15])=[O:11])=[C:8]([O:23][CH3:24])[CH:7]=1.N1C=CC=CC=1>C1C=CC=CC=1>[F:5][C:6]1[CH:22]=[CH:21][C:9]([C:10]([C:12]2[CH:20]=[CH:19][CH:18]=[CH:17][C:13]=2[C:14]([Cl:3])=[O:15])=[O:11])=[C:8]([O:23][CH3:24])[CH:7]=1 | COc1cc(F)ccc1C(=O)c1ccccc1C(=O)O | O=S(Cl)Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | c1ccccc1 | c1ccncc1 | null | null | null | null | null | null | null | null | null | null | null | Thionyl chloride (1.5 ml) was added to a solution of 2-(4-fluoro-2-methoxybenzoyl)benzoic acid (mp 119°-120° C.) (3.66 g) and pyridine (0.03 ml) in benzene (50 ml), followed by refluxing for an hour. The solvent was distilled off to give 2-(4-fluoro-2-methoxybenzoyl)benzoyl chloride (IRνmaxNujol : 1795 cm-1). A solution of this product in methylene chloride (40 ml) was added to a solution of ethyl 4-isopropylaminocrotonate (Reference Example I) (3.6 g) and triethylamine (3.0 ml) in methylene chloride (40 ml), followed by stirring at room temperature for 16 hours. After removing the solvent, ethyl acetate was added to the residue. The mixture was washed with water, dil. hydrochloric acid, water, sodium hydrogen carbonate solution and water in turn. The ethyl acetate layer was dried over anhydrous sodium sulfate and distilled to give the title compound (5.50 g) as pale brown oily substance. | COc1cc(F)ccc1C(=O)c1ccccc1C(=O)Cl | null | null | null |
577,308 | ord_dataset-a9ba4801408c4b01922886164c10a391 | null | 2003-01-01T00:01:00 | true | Br[CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][C:15]=1[F:16])[N:12]([C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=1)[CH:11]=[CH:10]2.[CH2:24]([NH:26][CH2:27][CH2:28][OH:29])[CH3:25]>>[Cl:23][C:20]1[CH:21]=[CH:22][C:17]([N:12]2[C:13]3[C:9](=[CH:8][C:7]([O:6][CH2:5][CH2:4][CH2:3][CH2:2][N:26]([CH2:24][CH3:25])[CH2:27][CH2:28][OH:29])=[C:15]([F:16])[CH:14]=3)[CH:10]=[CH:11]2)=[CH:18][CH:19]=1 | CCNCCO | Fc1cc2c(ccn2-c2ccc(Cl)cc2)cc1OCCCCBr | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | In analogy to example 23.7, 5-(4-Bromo-butoxy)-1-(4-chloro-phenyl)-6-fluoro-1H-indole and 2-(ethylamino)ethanol were converted to yield 2-({4-[1-(4-Chloro-phenyl)-6-fluoro-1H-indol-5-yloxy]-butyl}-ethyl-amino)-ethanol as a colorless oil, MS: 405 (MH+). | CCN(CCO)CCCCOc1cc2ccn(-c3ccc(Cl)cc3)c2cc1F | null | null | null |
300,918 | ord_dataset-9ad0840101374618a7d5c4e4521c82d1 | null | 1994-01-01T00:12:00 | true | [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@:9]1([C@@H:12](O)[CH3:13])[CH2:11][O:10]1.[CH3:15][C:16]1[N:17]([C:22]2[CH:27]=[CH:26][C:25]([O:28][C:29]([F:34])([F:33])[CH:30]([F:32])[F:31])=[CH:24][CH:23]=2)[C:18](=[O:21])[NH:19][N:20]=1>>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@:9]1([O:10][CH2:11]1)[C@H:12]([N:19]1[C:18](=[O:21])[N:17]([C:22]2[CH:23]=[CH:24][C:25]([O:28][C:29]([F:33])([F:34])[CH:30]([F:31])[F:32])=[CH:26][CH:27]=2)[C:16]([CH3:15])=[N:20]1)[CH3:13] | C[C@H](O)[C@@]1(c2ccc(F)cc2F)CO1 | Cc1n[nH]c(=O)n1-c1ccc(OC(F)(F)C(F)F)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | In the same manner as in Reference Example 5, starting from 0.50 g of (1S)-1-[(2R)-(2,4-difluorophenyl)-2-oxiranyl]ethanol and 0.58 g of 5-methyl-4-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-3(2H,4H)-1,2,4-triazolone, 0.46 g of 2-[(1R,2S)-2-(2,4-difluorophenyl)-2,3-epoxy-1-methylpropyl]-5-methyl-4-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-3(2H,4H)-1,2,4-triazolone was obtained as a colorless oil. | Cc1nn([C@H](C)[C@@]2(c3ccc(F)cc3F)CO2)c(=O)n1-c1ccc(OC(F)(F)C(F)F)cc1 | null | 48.8 | null |
956,639 | ord_dataset-ed65749688da45af8a8432967b017729 | null | 2010-01-01T00:05:00 | true | [NH2:1][CH2:2][C:3]1[N:4]=[C:5]([N:13]2[CH2:18][CH2:17][CH:16]([NH:19][C:20]([C:22]3[NH:23][C:24]([CH3:29])=[C:25]([Cl:28])[C:26]=3[Cl:27])=[O:21])[CH2:15][CH2:14]2)[S:6][C:7]=1[C:8]([O:10]CC)=[O:9].[CH2:30]([N:32]=[C:33]=[O:34])[CH3:31]>>[Cl:27][C:26]1[C:25]([Cl:28])=[C:24]([CH3:29])[NH:23][C:22]=1[C:20]([NH:19][CH:16]1[CH2:15][CH2:14][N:13]([C:5]2[S:6][C:7]([C:8]([OH:10])=[O:9])=[C:3]([CH2:2][NH:1][C:33]([NH:32][CH2:30][CH3:31])=[O:34])[N:4]=2)[CH2:18][CH2:17]1)=[O:21] | CCN=C=O | CCOC(=O)c1sc(N2CCC(NC(=O)c3[nH]c(C)c(Cl)c3Cl)CC2)nc1CN | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The title compound was prepared in a manner analogous to Example 250 from ethyl 4-(aminomethyl)-2-(4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}piperidin-1-yl)-1,3-thiazole-5-carboxylate (Example 246) and ethyl isocyanate. | CCNC(=O)NCc1nc(N2CCC(NC(=O)c3[nH]c(C)c(Cl)c3Cl)CC2)sc1C(=O)O | null | null | null |
249,827 | ord_dataset-4f3b2ca6df1d41ef8b5008f1f39da0e2 | null | 1992-01-01T00:06:00 | true | [Cl-].[Cl-].[Cl-].[Al+3].[CH3:5][O:6][C:7]1[CH:15]=[CH:14][C:10]([C:11](Cl)=[O:12])=[CH:9][CH:8]=1.[CH3:16][O:17][C:18]1[CH:30]=[C:29]([O:31][CH3:32])[CH:28]=[CH:27][C:19]=1[CH2:20][CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23]>ClCCCl>[CH3:16][O:17][C:18]1[CH:30]=[C:29]([O:31][CH3:32])[C:28]([C:11](=[O:12])[C:10]2[CH:14]=[CH:15][C:7]([O:6][CH3:5])=[CH:8][CH:9]=2)=[CH:27][C:19]=1[CH2:20][CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23] | COc1ccc(C(=O)Cl)cc1 | CCOC(=O)CCc1ccc(OC)cc1OC | null | [Al+3] | [Cl-] | 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 | 52 g of aluminum trichloride are suspended in 200 ml of 1,2-dichloroethane and cooled to 0° C. Then, at this temperature, 66.5 g of 4-methoxybenzoyl chloride are added dropwise, followed by 94.7 g of ethyl 2,4-dimethoxyhydrocinnamate in 30 ml of 1,2-dichloroethane. The mixture is then heated at 50° C. with exclusion of moisture until the reaction is complete. The reaction mixture is then poured onto ice-water, and the organic phase is separated off, diluted with 200 ml of methylene chloride and then extracted with sodium bicarbonate solution and water. It is dried over magnesium sulfate and concentrated. A gray-brown solid remains and is immediately reacted further. | CCOC(=O)CCc1cc(C(=O)c2ccc(OC)cc2)c(OC)cc1OC | null | null | null |
828,397 | ord_dataset-47bd90bf5ec74fcd99ce250a56e18c8f | null | 2008-01-01T00:07:00 | true | CN(CCN(C)C)C.C([Li])CCC.[Cl:14][C:15]1[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=1.CN([CH:24]=[O:25])C>CCOCC>[Cl:14][C:15]1[C:16]([CH:24]=[O:25])=[N:17][CH:18]=[CH:19][CH:20]=1 | Clc1cccnc1 | CN(C)C=O | null | CN(C)CCN(C)C | [Li]CCCC | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOCC | null | null | null | null | null | null | null | null | null | null | null | 0.5 | To a solution of TMEDA (660 μL, 2.58 mmol) in ether (20 mL) at −78° C. was added a solution of n-butyl lithium in ether (2.5 M, 1.76 mL, 4.40 mmol). After 30 minutes at −78° C., 3-chloropyridine (419 μL, 4.40 mmol) was added. After another 2 hours at −78° C., DMF (375 μL, 4.84 mmol) was added. After a further 2 hours at −78° C., the reaction was quenched with saturated aqueous NaHCO3 (20 mL), extracted with ether (4×15mL), dried (Na2SO4), filtered and concentrated in vacuo to give the crude oil. Purification by column chromatography on silica gel (Hexanes:EtOAc 4:1) afforded the title compound as a crystalline solid (168 mg, 27%). 1H NMR (CDCl3) 7.45 (dd, 1H, J=8.3, 4.4 Hz), 7.83 (dd, 1H, J=4.8, 1.4 Hz), 8.70 (dd, 1H, J=4.8, 1.5 Hz), 10.28 (s, 1H). | O=Cc1ncccc1Cl | null | 27 | null |
1,479,385 | ord_dataset-c3c1091f873b4f40827973a6f1f9b685 | null | 2014-01-01T00:09:00 | true | [CH2:1]([O:3][C:4](=[O:14])[CH:5]([O:9][CH2:10][C:11]([CH3:13])=[CH2:12])[CH2:6]C=C)[CH3:2]>C(Cl)Cl>[CH2:1]([O:3][C:4]([CH:5]1[CH2:6][CH:13]=[C:11]([CH3:12])[CH2:10][O:9]1)=[O:14])[CH3:2] | C=CCC(OCC(=C)C)C(=O)OCC | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | 25 | 0.83 | To a refluxing stirred solution of 2-(2-methyl-allyloxy)-pent-4-enoic acid ethyl ester (396 mg, 2.0 mmol) in CH2Cl2 (100 mL, 0.02 M solution) was added drop wise a solution of the tricyclohexylphosphine (1,3-Bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene)(benzylidine)ruthenium (IV)dichloride (85 mg, 0.1 mmol) in CH2Cl2 (3.0 mL). After 50 min, the reaction mixture was cooled to room temperature, concentrated and purified on silica gel bond elute using EtOAc/hexane (1:20) as an eluent furnished 5-methyl-3,6-dihydro-2H-pyran-2-carboxylic acid ethyl ester (320 mg, 92% yield) as a brown oil. NMR 1H (CDCl3, 400 MHz): 5.51 (br s, 1H), 4.28-4.08 (m, 4H), 2.32 (brs, 3H), 1.29 (t, J=7.2, 3H). | CCOC(=O)C1CC=C(C)CO1 | null | 94 | null |
1,704,323 | ord_dataset-54347fcace774f89850681d6dec8009f | null | 2016-01-01T00:03:00 | true | [O:1]([Si:9]([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10])S(C(F)(F)F)(=O)=O.[Br:16][C:17]1[CH:21]=[CH:20][O:19][C:18]=1[CH2:22]O.N1C=CC=CC=1>C(Cl)Cl>[Br:16][C:17]1[CH:21]=[CH:20][O:19][C:18]=1[CH2:22][O:1][Si:9]([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10] | OCc1occc1Br | CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | c1ccncc1 | null | null | null | null | null | null | null | null | null | 0 | 1 | tert-Butyldimethylsilanyl triflate (17.13 g) was added slowly to a stirred, cooled solution of 3-bromo-2-hydroxymethylfuran (Intermediate 39, 10.1 g) in DCM (160 mL) and pyridine (9.57 g) while maintaining the temperature at 0° C. The mixture was allowed to warm to room temperature and stirred for 1 hour. The mixture was washed with aqueous citric acid solution, brine, dried (Na2SO4) and filtered. The filtrate was evaporated to dryness to give 3-bromo-2-(tert-butyldimethylsilanyloxymethyl)furan (17.1 g). | CC(C)(C)[Si](C)(C)OCc1occc1Br | null | 102.9 | null |
1,135,781 | ord_dataset-aaeaab5f3720492494c1cbbdd0ed2820 | null | 2012-01-01T00:02:00 | true | [CH3:1][C:2]1[CH:3]=[C:4]([CH:9]2[CH2:14][N:13]([C:15]([N:17]3[CH2:22][CH2:21][CH:20]([OH:23])[CH2:19][CH2:18]3)=[O:16])[CH2:12][CH:11]([C:24](O)=[O:25])[CH2:10]2)[CH:5]=[CH:6][C:7]=1[CH3:8].O[N:28]=[C:29]([NH2:31])[CH3:30]>>[CH3:1][C:2]1[CH:3]=[C:4]([CH:9]2[CH2:10][CH:11]([C:24]3[O:25][N:31]=[C:29]([CH3:30])[N:28]=3)[CH2:12][N:13]([C:15]([N:17]3[CH2:22][CH2:21][CH:20]([OH:23])[CH2:19][CH2:18]3)=[O:16])[CH2:14]2)[CH:5]=[CH:6][C:7]=1[CH3:8] | Cc1ccc(C2CC(C(=O)O)CN(C(=O)N3CCC(O)CC3)C2)cc1C | CC(N)=NO | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | 200 mg (0.54 mmol) of the compound from Example 128A and 62 mg (0.81 mmol) of N′-hydroxyacetamidine were reacted according to the General Method 2. Yield: 154 mg (69% of theory) | Cc1noc(C2CC(c3ccc(C)c(C)c3)CN(C(=O)N3CCC(O)CC3)C2)n1 | null | null | null |
202,237 | ord_dataset-19e5fc80c1554f4f8641c835e055f02b | null | 1990-01-01T00:01:00 | true | [CH2:1](Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:9]([NH:12][CH2:13][CH2:14][CH3:15])[CH2:10][CH3:11]>CCOCC>[CH2:9]([N:12]([CH2:13][CH2:14][CH3:15])[CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH2:10][CH3:11] | CCCNCCC | BrCc1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOCC | null | null | null | null | null | null | null | null | null | null | null | null | An 11.9 ml portion of benzyl bromide and 41 ml of dipropylamine in ether were reacted as described in Example 3, giving 17.6 g of N,N-dipropylbenzenemethanamine as a clear liquid. | CCCN(CCC)Cc1ccccc1 | null | null | null |
856,034 | ord_dataset-faa0236be76c4501841c954527cd1b6c | null | 2008-01-01T00:12:00 | true | [C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH2:15][C@H:14]3[N:11]([C:12](=[O:19])[C@@H:13]3[C@H:16]([OH:18])[CH3:17])[C:10]=2[C:20]([O-:22])=[O:21])=[CH:5][CH:4]=1)#[N:2].[Na+].Cl[CH2:25][CH2:26][N:27]1[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1>CN(C=O)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH2:15][C@H:14]3[N:11]([C:12](=[O:19])[C@@H:13]3[C@H:16]([OH:18])[CH3:17])[C:10]=2[C:20]([O:22][CH2:25][CH2:26][N:27]2[CH2:32][CH2:31][O:30][CH2:29][CH2:28]2)=[O:21])=[CH:5][CH:4]=1)#[N:2] | ClCCN1CCOCC1 | C[C@@H](O)[C@H]1C(=O)N2C(C(=O)[O-])=C(c3ccc(C#N)cc3)C[C@H]12 | null | CCCC[N+](CCCC)(CCCC)CCCC | [I-] | [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 | null | null | Sodium (5R,6S)-3-(4-cyanophenyl)-6-[(1R)-1-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (0.2 g) in dry DMF (4.0 ml) was ice-cooled. Thereto ware added tetrabutylammonium iodide (0.53 g), and 4-(2-chloroethyl)-morpholine (1M toluene, 8 mL), and the mixture was stirred. Thirty minutes later, after removal of the bath the mixture was stirred for 48 hours and thereto was added ethyl acetate. The mixture was washed succesively with aqueous phosphate buffer (pH 6.86), water and brine. The organic layer was dried over sodium sulfate, concentrated, and the residue was purified with silica gel column chromatography (chloroform:methanol=1:0→10:1) to give 2-morpholin-4-ylethyl(5R,6S)-3-(4-cyanophenyl)-6-[(1R)-1-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (0.10 g, yield 33%). | C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCCN3CCOCC3)=C(c3ccc(C#N)cc3)C[C@H]12 | null | 33 | null |
1,527,491 | ord_dataset-8c74302143c04eb9983e4b3a7ead2d72 | null | 2014-01-01T00:12:00 | true | [N+:1]([O-:4])(O)=[O:2].[F:5][C:6]1[CH:16]=[C:15]([F:17])[CH:14]=[CH:13][C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9].OS(O)(=O)=O>>[F:5][C:6]1[CH:16]=[C:15]([F:17])[C:14]([N+:1]([O-:4])=[O:2])=[CH:13][C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9] | CCOC(=O)c1ccc(F)cc1F | O=[N+]([O-])O | null | O=S(=O)(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 | 2 | Conc. HNO3 (8 mL) was added dropwise to a mixture of ethyl 2,4-difluorobenzoate (10.0 g; 53.7 mmol) in cone. H2SO4 (8 mL) at 0° C. After 2 h at 0° C., the mixture was poured onto ice and extracted with EtOAc. The organic extracts were washed with saturated NaHCO3 solution (aq) and concentrated to give the sub-title compound. Yield: 11.8 g (95%). | CCOC(=O)c1cc([N+](=O)[O-])c(F)cc1F | null | null | null |
1,140,030 | ord_dataset-68715347640045adb1b09e6a04722b0e | null | 2012-01-01T00:03:00 | true | Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[CH:4][N:3]=1.[CH3:9][CH:10]1[CH2:15][CH:14]([CH3:16])[CH2:13][NH:12][CH2:11]1>>[Cl:8][C:6]1[CH:7]=[C:2]([N:12]2[CH2:13][CH:14]([CH3:16])[CH2:15][CH:10]([CH3:9])[CH2:11]2)[N:3]=[CH:4][N:5]=1 | Clc1cc(Cl)ncn1 | CC1CNCC(C)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 | 5 | 0.3 g of 4,6-dichloropyrimidine and 0.34 g of 3,5-dimethylpiperidine (cis/trans diastereomer=about 3/1) were mixed and left for 5 hours at room temperature. The reaction mixture was subjected to silica gel column chromatography to obtain 0.3 g of 4-chloro-6-(3,5-dimethylpiperidino)pyrimidine. This compound had the cis/trans diastereomer originated two methyls on the pyperidine ring. The ratio of the cis/trans diastereomer was about 3.1/1. | CC1CC(C)CN(c2cc(Cl)ncn2)C1 | null | 66 | null |
1,146,392 | ord_dataset-68715347640045adb1b09e6a04722b0e | null | 2012-01-01T00:03:00 | true | [S:1]1[C:5]2[CH:6]=[C:7]([C:10]3([C:13]4[N:17]5[N:18]=[C:19]([C:22]6[CH:31]=[CH:30][C:25]([C:26]([O:28]C)=[O:27])=[CH:24][CH:23]=6)[CH:20]=[N:21][C:16]5=[N:15][N:14]=4)[CH2:12][CH2:11]3)[CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.O.[OH-].[Li+].Cl>CO.O>[S:1]1[C:5]2[CH:6]=[C:7]([C:10]3([C:13]4[N:17]5[N:18]=[C:19]([C:22]6[CH:31]=[CH:30][C:25]([C:26]([OH:28])=[O:27])=[CH:24][CH:23]=6)[CH:20]=[N:21][C:16]5=[N:15][N:14]=4)[CH2:11][CH2:12]3)[CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1 | COC(=O)c1ccc(-c2cnc3nnc(C4(c5ccc6ncsc6c5)CC4)n3n2)cc1 | null | null | Cl | [Li+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CO | null | null | null | null | null | null | null | null | null | 25 | 4 | A mixture of methyl 4-{3-[1-(1,3-benzothiazol-6-yl)cyclopropyl][1,2,4]triazolo[4,3-b][1,2,4]triazin-6-yl}benzoate (80.0 mg, 0.19 mmol) and lithium hydroxide monohydrate (16.0 mg, 0.37 mmol) in methanol (3.0 mL) and water (1.0 mL) was stirred at RT for 4 h. The mixture was adjusted with 1N HCl to pH=5. The volatiles were removed under reduced pressure, and dried in-vacuo to give a crude product which was directly used in the next step without further purification. Analytical LCMS: (M+H)+=415.0. | O=C(O)c1ccc(-c2cnc3nnc(C4(c5ccc6ncsc6c5)CC4)n3n2)cc1 | null | null | null |
973,109 | ord_dataset-03ba810b7f464a06b5d8787af2e8b64e | null | 2010-01-01T00:06:00 | true | [C:1]([O:4][C@H:5]1[C@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8](OC(=N)C(Cl)(Cl)Cl)[O:7][CH:6]1[CH2:26][O:27][C:28](=[O:30])[CH3:29])(=[O:3])[CH3:2].[Cl:31][C:32]1[CH:33]=[N:34][CH:35]=[C:36]([Cl:53])[C:37]=1[NH:38][C:39]1[C:48]2[C:43](=[C:44]([OH:51])[C:45]([O:49][CH3:50])=[CH:46][CH:47]=2)[O:42][C:41](=[O:52])[CH:40]=1>C(#N)C>[C:1]([O:4][C@H:5]1[C@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@H:8]([O:51][C:44]2[C:45]([O:49][CH3:50])=[CH:46][CH:47]=[C:48]3[C:43]=2[O:42][C:41](=[O:52])[CH:40]=[C:39]3[NH:38][C:37]2[C:36]([Cl:53])=[CH:35][N:34]=[CH:33][C:32]=2[Cl:31])[O:7][C@@H:6]1[CH2:26][O:27][C:28](=[O:30])[CH3:29])(=[O:3])[CH3:2] | CC(=O)OCC1O[C@H](OC(=N)C(Cl)(Cl)Cl)[C@@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O | COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1O | 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 | 25 | 2 | Boron trifluoride•OEt2 (54 μL, 0.43 mmol) was added to a suspension of (3R,4S,5S,6R)-2-(acetoxymethyl)-6-(2,2,2-trichloro-1-iminoethoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate (0.168 g, 0.341 mmol), 4-(3,5-dichloropyridin-4-ylamino)-8-hydroxy-7-methoxy-2H-chromen-2-one (60 mg, 0.17 mmol, Example 29), and anhydrous acetonitrile (2 mL) at −40° C. under N2. After 2 h at −40° C., the reaction was allowed to warm to rt and stirred overnight. The mixture was concentrated and purified by reverse-phase HPLC to give (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2-oxo-2H-chromen-8-yloxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate: 1H NMR (400 MHz, DMSO-d6): δ 9.55 (s, 1H), 8.83 (s, 2H), 8.03 (d, 1H), 7.25 (d, 1H), 5.34 (m, 2H), 5.08 (m, 1H), 4.98 (m, 1H), 4.67 (s, 1H), 4.12 (m, 1H), 3.99 (m, 2H), 3.91 (s, 3H), 2.06 (s, 3H), 1.98 (m, 6H), 1.94 (s, 3H); MS (ESI): 682.8. | COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1O[C@@H]1O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O | null | null | null |
9,377 | ord_dataset-ad879e603f9440f6bfb7fbd18e5e8761 | null | 1976-01-01T00:06:00 | true | [CH3:1][O:2][C:3]([CH3:19])([CH3:18])[CH2:4][CH2:5][CH2:6][CH:7]([CH3:17])[CH2:8][CH:9]=[CH:10][CH:11]=[C:12]([CH3:16])[C:13]([OH:15])=[O:14].[CH2:20](Br)[C:21]#[CH:22]>>[CH2:22]([O:14][C:13](=[O:15])[C:12]([CH3:16])=[CH:11][CH:10]=[CH:9][CH2:8][CH:7]([CH3:17])[CH2:6][CH2:5][CH2:4][C:3]([O:2][CH3:1])([CH3:18])[CH3:19])[C:21]#[CH:20] | COC(C)(C)CCCC(C)CC=CC=C(C)C(=O)O | C#CCBr | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Utilizing the procedure of Example 15, 11-methoxy-2,7,11-trimethyl-2,4-dodecadienoic acid and propargyl bromide are reacted. After chromatography on Kieselgel, using diethyl ether/petroleum ether (1:3 parts by volume) as the eluant, there is obtained 11-methoxy-2,7,11-trimethyl-2,4-dodecadienoic acid propargyl ester in pure form; boiling point 110°C/0.002 mmHg. | C#CCOC(=O)C(C)=CC=CCC(C)CCCC(C)(C)OC | null | null | null |
109,744 | ord_dataset-406d20cb3f314e2c967b14f55925f895 | null | 1983-01-01T00:10:00 | true | [CH3:1][O:2][C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[CH3:13])[C:4]=1[C:14]([F:17])([F:16])[F:15].[Br:18]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl>[Br:18][CH2:13][C:9]1[CH:8]=[CH:7][CH:6]=[C:5]2[C:10]=1[CH:11]=[CH:12][C:3]([O:2][CH3:1])=[C:4]2[C:14]([F:16])([F:15])[F:17] | COc1ccc2c(C)cccc2c1C(F)(F)F | O=C1CCC(=O)N1Br | null | O=C(OOC(=O)c1ccccc1)c1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClC(Cl)(Cl)Cl | null | null | null | null | null | null | null | null | null | null | null | null | A suspension of 2-methoxy-5-methyl-1-(trifluoromethyl)naphthalene (1.2 g, 5.0 mmol), N-bromosuccinimide (1.07 g, 6.0 mmol) and benzoyl peroxide (20-30 mg) in carbon tetrachloride (10 mL) was heated at reflux for 1.5 hr. The residual solid in the reaction mixture was removed by filtration, and the collected solid on the filter was washed with methylene chloride. The combined filtrates were washed with water, dried (MgSO4) and evaporated to give 1.7 g of 5-(bromomethyl)-1-(trifluoromethyl)-2-methoxynaphthalene (IX, R=CH3 and R1 =CH2Br) which was used in the next step without purification. Crystallization of a sample from hexane furnished pure 5-(bromomethyl)-1-trifluoromethyl-2-methoxynaphthalene having mp 97°-99° C.; nmr (CDCl3) δ 3.95 (s, 3H), 4.85 (s, 2H), 7.7 (m, 5H); ir (CHCl3) 1265, 1125 cm-1 ; uvλmax (MeOH) 339 nm (ε3,510), 326 (3,280), 300 (7,230), 288 (7,150), 229 (44,150); anal Calcd for C13H10BrF3O: C, 48.93% H, 3.16%; Found: C, 48.88% H, 3.14%. | COc1ccc2c(CBr)cccc2c1C(F)(F)F | null | 106.5 | null |
91,875 | ord_dataset-dba7c8cf38834984ba5e6376158f46fe | null | 1982-01-01T00:03:00 | true | Br[CH2:2][CH:3]1[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.CC(C)([O-])C.[K+].[NH:16]1[CH:20]=[CH:19][N:18]=[CH:17]1>C(O)CCC>[CH:3]1([CH2:2][N:16]2[CH:20]=[CH:19][N:18]=[CH:17]2)[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1 | c1c[nH]cn1 | BrCC1CCCCCC1 | null | CC(C)(C)[O-] | [K+] | 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 | 7 | Bromomethylcycloheptane (5.3 g, 0.0278 mol) was added dropwise to a stirred solution of potassium t-butoxide (3.1 g, 0.0277 mol) and imidazole (1.9 g, 0.0279 mol) in dry n-butanol (50 ml) maintained at 100° and under dry nitrogen. After the addition (~20 mins) the temperature of the reaction mixture was raised to boiling. The reaction mixture was then stirred and boiled for 7 h and then cooled. | c1cn(CC2CCCCCC2)cn1 | null | null | null |
999,943 | ord_dataset-70899a0178cc441482746c093624afa0 | null | 2010-01-01T00:10:00 | true | [CH2:1]([N:3]([CH2:15][CH3:16])[C:4](=[O:14])[C:5]1[CH:10]=[CH:9][C:8]([CH2:11][CH2:12][CH3:13])=[CH:7][CH:6]=1)[CH3:2].C([Li])(CC)C.[CH3:22][S:23]SC>C1COCC1>[CH2:15]([N:3]([CH2:1][CH3:2])[C:4](=[O:14])[C:5]1[CH:10]=[CH:9][C:8]([CH2:11][CH2:12][CH3:13])=[CH:7][C:6]=1[S:23][CH3:22])[CH3:16] | CCCc1ccc(C(=O)N(CC)CC)cc1 | CSSC | null | [Li]C(C)CC | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | null | 0.5 | To a stirring solution of N,N-diethyl-4-propylbenzamide (2.0 g, 9.3 mmol) and N,N,N′N′-tetramethylethylenediamine (1085 mg, 9.4 mmol) in dry THF (93 mL) at −78° C. under Ar was added 0.78 M s-butyllithium in hexanes (12 mL). The reaction was stirred for 30 min and then methyl disulfide (1936 mg, 12.1 mmol) was added. The reaction was stirred for 5 min and then quenched with MeOH (1 mL) and brine. The reaction was extracted with EtOAc (3×50 mL). The organic layers were combined, dried over Na2SO4, and conc in vacuo to a yellow oil. The oil was purified by flash chromatography (SiO2, 0-30% EtOAc in hexanes) to yield 2.1 g (86%) of the product as a yellow oil. MS (ESI) 266 (M+H). | CCCc1ccc(C(=O)N(CC)CC)c(SC)c1 | null | 85.1 | null |
193,789 | ord_dataset-b83b16f2fb1a4f8782f3d82c1766cc6b | null | 1989-01-01T00:08:00 | true | [CH2:1]([N:8]([C:13]1[N:21]=[CH:20][N:19]=[C:18]2[C:14]=1[N:15]=[CH:16][N:17]2C1CCCCO1)[CH2:9][CH:10]([CH3:12])[CH3:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.N>O>[CH2:1]([N:8]([C:13]1[N:21]=[CH:20][N:19]=[C:18]2[C:14]=1[NH:15][CH:16]=[N:17]2)[CH2:9][CH:10]([CH3:12])[CH3:11])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1 | CC(C)CN(Cc1ccccc1)c1ncnc2c1ncn2C1CCCCO1 | null | null | Cl | N | 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 | 8 | A solution of 17.0 g. (47 mmole) 6-[N-benzyl-N-(2-methylpropyl)-amino]-9-tetrahydropyran-2-ylpurine (compound of Example 1) in 200 ml. saturated ethanolic hydrogen chloride solution is heated under reflux for 10 minutes. After standing overnight, the reaction mixture is diluted with water, adjusted to pH 7 with aqueous ammonia solution and the precipitate filtered off with suction. After recrystallization from aqueous propan-2-ol, there are obtained 10.5 g. of the title compound (80% of theory); m.p. 160°-162° C. | CC(C)CN(Cc1ccccc1)c1ncnc2nc[nH]c12 | null | 80 | null |
321,498 | ord_dataset-eed8d32c2f1d46a89ba39d04dfaa83b1 | null | 1995-01-01T00:12:00 | true | CCN(S(F)(F)[F:7])CC.[C:10]([O:14][P:15]([CH:22](O)[C:23]1[CH:45]=[CH:44][C:26]([CH2:27][CH:28]([C:40]([O:42][CH3:43])=[O:41])[NH:29][C:30]([O:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)=[O:31])=[CH:25][CH:24]=1)([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])([CH3:13])([CH3:12])[CH3:11]>C(Cl)(Cl)Cl.[Cl-].[Na+].O>[C:10]([O:14][P:15]([CH:22]([F:7])[C:23]1[CH:45]=[CH:44][C:26]([CH2:27][CH:28]([C:40]([O:42][CH3:43])=[O:41])[NH:29][C:30]([O:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)=[O:31])=[CH:25][CH:24]=1)([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])([CH3:13])([CH3:12])[CH3:11] | COC(=O)C(Cc1ccc(C(O)P(=O)(OC(C)(C)C)OC(C)(C)C)cc1)NC(=O)OCc1ccccc1 | CCN(CC)S(F)(F)F | null | [Cl-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | ClC(Cl)Cl | null | null | null | null | null | null | null | null | null | 25 | 0.17 | To DAST (0.15 mL, 1.1 mmol) in anhydrous CHCl3 (0.6 mL) at -78° C. was slowly added compound 9 (536 mg, 1.0 mmol) in CHCl3 (2.0 mL). After 10 minutes, the reaction mixture was warmed to ambient temperature and stirred (20 minutes). The mixture was slowly diluted with brine (10 mL) then extracted with CHCl3 (2×10 mL) and the combined extracts dried (MgSO4) and evaporated under reduced pressure to yield crude 20 (629 mg). Purification by silica gel chromatography afforded pure 20 as a syrup (295 mg, 55%). | COC(=O)C(Cc1ccc(C(F)P(=O)(OC(C)(C)C)OC(C)(C)C)cc1)NC(=O)OCc1ccccc1 | null | 117 | null |
1,658,694 | ord_dataset-42cd9bc5aae3485f9a58f1527bd3abf0 | null | 2015-01-01T00:11:00 | true | [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[O:12][CH:13]=[CH:14][CH:15]=2)=[O:10])=[CH:4][C:3]=1[C:16]1[NH:17][C:18]2[C:19]([N:27]=1)=[N:20][CH:21]=[C:22]([N+:24]([O-])=O)[CH:23]=2.O.O.Cl[Sn]Cl>C(O)C>[NH2:24][C:22]1[CH:23]=[C:18]2[NH:17][C:16]([C:3]3[CH:4]=[C:5]([NH:8][C:9]([C:11]4[O:12][CH:13]=[CH:14][CH:15]=4)=[O:10])[CH:6]=[CH:7][C:2]=3[Cl:1])=[N:27][C:19]2=[N:20][CH:21]=1 | O=C(Nc1ccc(Cl)c(-c2nc3ncc([N+](=O)[O-])cc3[nH]2)c1)c1ccco1 | null | null | Cl[Sn]Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | O | null | null | null | null | null | null | null | null | null | null | null | To a suspension of N-(4-chloro-3-[6-nitro-1H-imidazo[4,5-b]pyridin-2-yl]phenyl)furan-2-carboxamide (3.9 g, 10.16 mmol, 1.00 equiv) in ethanol (50 mL) was added SnCl2.2H2O (3.4 g, 15.04 mmol, 1.48 equiv) and heated to reflux overnight. The reaction mixture was concentrated under vacuum and diluted with H2O. The pH value of the mixture was adjusted to 9 with sodium carbonate (sat.). The solids were collected by filtration and applied onto a silica gel column with ethyl acetate/PE (3/1) to give 1.95 g (54%) of N-(3-[6-amino-1H-imidazo[4,5-b]pyridin-2-yl]-4-chlorophenyl)furan-2-carboxamide as a yellow solid. 1H-NMR: (CD3OD, 400 MHz): 8.16 (d, J=2.4 Hz, 1H), 7.97-8.10 (m, 2H), 7.78 (d, J=0.8 Hz, 1H), 7.65 (d, J=20.0 Hz, 1H), 7.31-7.41 (m, 2H), 6.68 (dd, J=3.6, 2.0 Hz, 1H. MS (M+H)+=354. | Nc1cnc2nc(-c3cc(NC(=O)c4ccco4)ccc3Cl)[nH]c2c1 | null | 54.3 | null |
1,621,169 | ord_dataset-35c51552812941cda45194a013d34bb9 | null | 2015-01-01T00:08:00 | true | [CH:1]1([NH:4][C:5]2[S:9][C:8]([C:10]3[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=3)=[N:7][CH:6]=2)[CH2:3][CH2:2]1.[Cl:16]N1C(=O)CCC1=O>C(#N)C>[Cl:16][C:6]1[N:7]=[C:8]([C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)[S:9][C:5]=1[NH:4][CH:1]1[CH2:3][CH2:2]1 | c1cncc(-c2ncc(NC3CC3)s2)c1 | O=C1CCC(=O)N1Cl | 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 | 0 | 1 | To a solution of N-cyclopropyl-2-(pyridin-3-yl)thiazol-5-amine (1.00 g, 4.60 mmol) in acetonitrile (2 mL) was added 1-chloropyrrolidine-2,5-dione (645 mg, 4.83 mmol) and the mixture stirred at 0° C. for 1 h. The mixture was filtered and the filtrate was treated with excess HCl (4M in dioxane) to give 4-chloro-N-cyclopropyl-2-(pyridin-3-yl)thiazol-5-amine as a brown solid: mp 56-60° C. | Clc1nc(-c2cccnc2)sc1NC1CC1 | null | null | null |
1,101,768 | ord_dataset-af85e6f81c2d49f08086afd6d9e6959c | null | 2011-01-01T00:10:00 | true | C([O:8][C:9]1[CH:10]=[CH:11][C:12]2[N:16]=[CH:15][N:14]([C:17]3[S:18][C:19]([C:29]([NH2:31])=[O:30])=[C:20]([C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[CH:23]=4)[N:21]=3)[C:13]=2[CH:32]=1)C1C=CC=CC=1.ClCCl>O>[Cl:28][C:24]1[CH:23]=[C:22]([C:20]2[N:21]=[C:17]([N:14]3[C:13]4[CH:32]=[C:9]([OH:8])[CH:10]=[CH:11][C:12]=4[N:16]=[CH:15]3)[S:18][C:19]=2[C:29]([NH2:31])=[O:30])[CH:27]=[CH:26][CH:25]=1 | NC(=O)c1sc(-n2cnc3ccc(OCc4ccccc4)cc32)nc1-c1cccc(Cl)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | ClCCl | null | null | null | null | null | null | null | null | null | 25 | 1 | To a mixture of 3.2 g (6.96 mmole) of 2-(6-benzyloxy-benzoimidazol-1-yl)-4-(3-chloro-phenyl)-thiazole-5-carboxylic acid amide (I.25c) and 50 mL of dichloromethane at 0 degrees was added, dropwise, 5.86 mL (56 mmole) of boron trifluoride-dimethylsulfide complex. The mixture was stirred at ambient temperature for 1 hour and then 50 mL of water was added. The mixture was stirred vigorously for 1 hour. The precipitate was collected by filtration to give 2.6 g of 4-(3-chloro-phenyl)-2-(6-hydroxy-benzoimidazol-1-yl)-thiazole-5-carboxylic acid amide (I.25d) as an off-white solid. | NC(=O)c1sc(-n2cnc3ccc(O)cc32)nc1-c1cccc(Cl)c1 | null | 100.7 | null |
1,418,317 | ord_dataset-f8e6e6a2d2bf4135b9e346456c81700f | null | 2014-01-01T00:04:00 | true | [Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]3[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][C:7]=3[NH:8]2)=[CH:4][CH:3]=1.[H-].[Na+].[CH3:24]I>CN(C=O)C.C(Cl)Cl>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]3[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][C:7]=3[N:8]2[CH3:24])=[CH:4][CH:3]=1 | CC(C)(C)OC(=O)N1CCc2c([nH]c3cc(Br)ccc23)C1 | CI | null | [H-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | ClCCl | null | null | null | null | null | null | null | null | null | null | 0.5 | tert-Butyl 7-bromo-3,4-dihydro-1H-pyrido[3,4-b]indole-2(9H)-carboxylate (1.96 g, 5.58 mmol) was dissolved in DMF (20 mL), and sodium hydride (60% weight dispersion in mineral oil, 330 mg, 8.37 mmol) was added. After 30 minutes, methyl iodide (0.52 mL, 8.4 mmol) was added, and the reaction stirred for a further 2 h. The mixture was diluted with methylene chloride and washed with 5% lithium chloride solution (5×), dried and concentrated. Purification by flash column chromatography (silica gel, hexanes/ethyl acetate, 97:3 to 75:25) gave the title compound (1.75 g, 86%) as a white powder: 1H NMR (500 MHz, CD3OD) δ 7.41 (d, J=1.5 Hz, 1H), 7.32 (d, J=8.3 Hz, 1H), 7.18 (dd, J=8.4, 1.6 Hz, 1H), 4.60 (br s, 2H), 3.73 (br s, 2H), 3.59 (s, 3H), 2.76 (br s, 2H), 1.50 (s, 9H). | Cn1c2c(c3ccc(Br)cc31)CCN(C(=O)OC(C)(C)C)C2 | null | 85.9 | null |
1,626,813 | ord_dataset-f0794d5ded7a4d3fab45cc3d7a89ee3d | null | 2015-01-01T00:09:00 | true | Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12]([CH:14]1[CH2:16][CH2:15]1)=[O:13])=[C:5]2[NH:17][C:18]1[CH:19]=[CH:20][C:21]([N:24]2[CH2:28][CH2:27][CH:26]([NH:29]C(=O)OC(C)(C)C)[CH2:25]2)=[N:22][CH:23]=1.[Cl:37][C:38]1[CH:43]=[C:42](B2OC(C)(C)C(C)(C)O2)[CH:41]=[C:40]([F:53])[C:39]=1[OH:54]>>[NH2:29][CH:26]1[CH2:27][CH2:28][N:24]([C:21]2[N:22]=[CH:23][C:18]([NH:17][C:5]3[C:4]4[C:9](=[CH:10][CH:11]=[C:2]([C:42]5[CH:41]=[C:40]([F:53])[C:39]([OH:54])=[C:38]([Cl:37])[CH:43]=5)[CH:3]=4)[N:8]=[CH:7][C:6]=3[C:12]([CH:14]3[CH2:15][CH2:16]3)=[O:13])=[CH:19][CH:20]=2)[CH2:25]1 | CC1(C)OB(c2cc(F)c(O)c(Cl)c2)OC1(C)C | CC(C)(C)OC(=O)NC1CCN(c2ccc(Nc3c(C(=O)C4CC4)cnc4ccc(Br)cc34)cn2)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 | Following general procedure D, tert-butyl 1-(5-(6-bromo-3-(cyclopropanecarbonyl)quinoline-4-ylamino)pyridin-2-yl)pyrrolidin-3-ylcarbamate (100 mg, 0.18 mmol) was reacted with 2-chloro-6-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (74 mg, 0.27 mmol) to obtain the protected intermediate which was subjected to general procedure A-2 to afford the desired product (21 mg, 23% over 2 steps) as a yellow-brown solid: 1H NMR (500 MHz, CD3OD+TFA-d) δ 9.36 (s, 1H), 8.27 (dd, J=8.8, 1.9 Hz, 1H), 8.24 (d, J=2.7 Hz, 2H), 8.06 (d, J=8.8 Hz, 1H), 7.90 (dd, J=9.4, 2.6 Hz, 1H), 7.27 (m, 2H), 7.08 (d, J=9.4 Hz, 1H), 4.16 (p, J=6.2 Hz, 1H), 4.05 (dd, J=11.9, 6.5 Hz, 1H), 3.88 (dt, J=10.8, 7.5 Hz, 1H), 3.79 (dt, J=10.5, 3.3 Hz, 2H), 2.81 (p, J=6.0 Hz, 1H), 2.61 (dq, J=13.3, 6.6 Hz, 1H), 2.33 (td, J=13.4, 5.3 Hz, 1H), 1.20 (m, 4H); ESI MS m/z 518 [C28H25ClFN5O2+H]+; HPLC 99.4% (AUC), tR=10.02 min. | NC1CCN(c2ccc(Nc3c(C(=O)C4CC4)cnc4ccc(-c5cc(F)c(O)c(Cl)c5)cc34)cn2)C1 | null | 22.5 | null |
732,498 | ord_dataset-76dd1b78ee414d2da0ed30700ef026f7 | null | 2006-01-01T00:10:00 | true | Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[O:13][N:12]=[C:11]([CH:14]3[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]3)[CH:10]=2)[CH:5]=[CH:4][N:3]=1.[CH3:20][O:21][C:22]1[CH:23]=[C:24]([CH:26]=[C:27]([O:31][CH3:32])[C:28]=1[O:29][CH3:30])[NH2:25]>>[CH3:32][O:31][C:27]1[CH:26]=[C:24]([NH:25][C:2]2[N:7]=[C:6]([NH:8][C:9]3[O:13][N:12]=[C:11]([CH:14]4[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]4)[CH:10]=3)[CH:5]=[CH:4][N:3]=2)[CH:23]=[C:22]([O:21][CH3:20])[C:28]=1[O:29][CH3:30] | Clc1nccc(Nc2cc(C3CCCCC3)no2)n1 | COc1cc(N)cc(OC)c1OC | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The title compound was prepared by the method described in Example 1 using 2-chloro-N4-(3-cyclohexylisoxazol-5-yl)-4-pyrimidineamine (Step C) and 3,4,5-trimethoxyaniline. MS (MH+)=426.5; Calc'd for C22H27N5O4— 425.49. | COc1cc(Nc2nccc(Nc3cc(C4CCCCC4)no3)n2)cc(OC)c1OC | null | null | null |
41,820 | ord_dataset-48929f64ce614f1181a555eafd7c97a6 | null | 1978-01-01T00:06:00 | true | [C:1]([S:20][C@@H:21]1[O:29][C@H:28]([CH2:30][OH:31])[C@@H:26]([OH:27])[C@H:24]([OH:25])[C@H:22]1[OH:23])([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:32][S:33](Cl)(=[O:35])=[O:34]>N1C=CC=CC=1>[C:1]([S:20][C@@H:21]1[O:29][C@H:28]([CH2:30][O:31][S:33]([CH3:32])(=[O:35])=[O:34])[C@@H:26]([O:27][S:33]([CH3:32])(=[O:35])=[O:34])[C@H:24]([O:25][S:33]([CH3:32])(=[O:35])=[O:34])[C@H:22]1[O:23][S:33]([CH3:32])(=[O:35])=[O:34])([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1 | OC[C@H]1O[C@@H](SC(c2ccccc2)(c2ccccc2)c2ccccc2)[C@H](O)[C@@H](O)[C@@H]1O | CS(=O)(=O)Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | c1ccncc1 | null | null | null | null | null | null | null | null | null | null | null | 22 | S-Trityl-1-thio-β-D-glucopyranose (3.6 g.) was dissolved in 50 ml. dry pyridine, cooled to 0° while 5 ml. (7.5 g.) of methylsulfonyl chloride was added. The solution was placed in the refrigerator for 22 hours until thin layer chromatography showed only traces of starting material or partially reacted products remaining. The solvent was removed at reduced pressure. The oily residue was dissolved in chloroform (200 ml.) and was washed with dilute hydrochloric acid and brine. Evaporating the dried organic extract yielded a product which was chromatographed over a silica dry-column using 20% ethyl acetate-80% chloroform eluant. Pure S-trityl-2,3,4,6-tetra-O-methylsulfonyl-1-thio-β-D-glucopyranose was obtained from ether. | CS(=O)(=O)OC[C@H]1O[C@@H](SC(c2ccccc2)(c2ccccc2)c2ccccc2)[C@H](OS(C)(=O)=O)[C@@H](OS(C)(=O)=O)[C@@H]1OS(C)(=O)=O | null | null | null |
149,489 | ord_dataset-f222e615b1f74f0fabef9cd9b98516b7 | null | 1986-01-01T00:10:00 | true | [OH:1][CH:2]1[CH2:6][CH2:5][O:4][CH2:3]1.C(N(CC)CC)C.[N+:14]([C:17]1[CH:25]=[CH:24][C:23]([O:26][C:27]2[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:29][C:28]=2[Cl:37])=[CH:22][C:18]=1[C:19](Cl)=[O:20])([O-:16])=[O:15]>C1(C)C=CC=CC=1>[N+:14]([C:17]1[CH:25]=[CH:24][C:23]([O:26][C:27]2[CH:32]=[CH:31][C:30]([C:33]([F:34])([F:35])[F:36])=[CH:29][C:28]=2[Cl:37])=[CH:22][C:18]=1[C:19]([O:1][CH:2]1[CH2:6][CH2:5][O:4][CH2:3]1)=[O:20])([O-:16])=[O:15] | OC1CCOC1 | O=C(Cl)c1cc(Oc2ccc(C(F)(F)F)cc2Cl)ccc1[N+](=O)[O-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(CC)CC | Cc1ccccc1 | null | null | null | null | null | null | null | null | null | null | 8 | 3-Hydroxytetrahydrofuran (1.76 grams; 0.02 mole), toluene (50 ml) and triethylamine (2.0 grams; 0.02 mole) were charged into a glass reaction vessel equipped with a mechanical stirrer and addition funnel. A solution of 2-nitro-5-(2-chloro-4-trifluoromethylphenoxy)benzoyl chloride (7.60 grams; 0.02 mole) in toluene (10 ml) was slowly added with stirring. After the addition was completed, stirring was continued overnight. After this time, the reaction mixture was washed with water and dried over anhydrous sodium sulfate. The dried solution was then stripped of solvent under reduced pressure leaving a brown oil. This oil was purified by silica gel chromatography using toluene and ethyl acetate/toluene mixtures as the eluant. The purified oil was triturated in ethanol to yield the desired product 3-tetrahydrofuryl 2-nitro-5-(2-chloro-4-trifluoromethylphenoxy)benzoate as a white solid, melting point at 55° C. | O=C(OC1CCOC1)c1cc(Oc2ccc(C(F)(F)F)cc2Cl)ccc1[N+](=O)[O-] | null | null | null |
1,612,462 | ord_dataset-9cecb3a8d3b9494191b28dcefea66af2 | null | 2015-01-01T00:07:00 | true | Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][N:11]=[C:10]([CH3:13])[C:9]=2[C@H:14]([OH:25])[CH2:15][S:16]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:17])=[CH:4][CH:3]=1.[CH2:26]([O:28][C:29]([C:31]1([C:34]2[CH:39]=[CH:38][C:37](B3OC(C)(C)C(C)(C)O3)=[CH:36][CH:35]=2)[CH2:33][CH2:32]1)=[O:30])[CH3:27]>>[CH2:26]([O:28][C:29]([C:31]1([C:34]2[CH:39]=[CH:38][C:37]([C:2]3[CH:7]=[CH:6][C:5]([C:8]4[O:12][N:11]=[C:10]([CH3:13])[C:9]=4[C@H:14]([OH:25])[CH2:15][S:16]([CH2:18][C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[O:17])=[CH:4][CH:3]=3)=[CH:36][CH:35]=2)[CH2:32][CH2:33]1)=[O:30])[CH3:27] | CCOC(=O)C1(c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)CC1 | Cc1noc(-c2ccc(Br)cc2)c1[C@H](O)CS(=O)Cc1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Prepared according to the procedure described in Example 110, Step 3, using (S)-1-[5-(4-bromo-phenyl)-3-methyl-isoxazol-4-yl]-2-phenylmethanesulfinyl-ethanol and 1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclopropanecarboxylic acid ethyl ester. | CCOC(=O)C1(c2ccc(-c3ccc(-c4onc(C)c4[C@H](O)CS(=O)Cc4ccccc4)cc3)cc2)CC1 | null | null | null |
797,445 | ord_dataset-a2d74266062e4398bc26c4f876903ab8 | null | 2007-01-01T00:11:00 | true | [CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([S:21]([CH3:24])(=[O:23])=[O:22])=[CH:17][C:16]=2[NH2:25])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:26]1(C)C=CC(S(O)(=O)=O)=CC=1>COC(OC)OC>[CH2:1]([N:8]1[CH2:9][CH2:10][CH:11]([N:14]2[C:15]3[CH:20]=[CH:19][C:18]([S:21]([CH3:24])(=[O:23])=[O:22])=[CH:17][C:16]=3[N:25]=[CH:26]2)[CH2:12][CH2:13]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1 | CS(=O)(=O)c1ccc(NC2CCN(Cc3ccccc3)CC2)c(N)c1 | Cc1ccc(S(=O)(=O)O)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | COC(OC)OC | null | null | null | null | null | null | null | null | null | null | null | null | The crude material from step 2 (130 g) was stirred in 300 mL trimethylorthoformate containing 4-toluenesulphonic acid (8 g) at 90° C. for one hour, and collecting the methanol distillate. The reaction was cooled and filtered to give 108 g 1-(1-benzylpiperidin-4-yl)-5-methylsulphonyl-1H-benzimidazole as a brown solid. | CS(=O)(=O)c1ccc2c(c1)ncn2C1CCN(Cc2ccccc2)CC1 | null | 629.2 | null |
1,327,207 | ord_dataset-cfad8b3f00044bcda60a96b019f09872 | null | 2013-01-01T00:08:00 | true | [CH3:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][C:5]([C:11]#[C:12][Si](C)(C)C)=[CH:4][N:3]=1.C(=O)([O-])[O-].[K+].[K+]>CO>[C:11]([C:5]1[CH:6]=[C:7]([N+:8]([O-:10])=[O:9])[C:2]([CH3:1])=[N:3][CH:4]=1)#[CH:12] | Cc1ncc(C#C[Si](C)(C)C)cc1[N+](=O)[O-] | null | null | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | 25 | 0.17 | A solution of 2-methyl-3-nitro-5-[(trimethylsilyl)ethynyl]pyridine (2.32 g, 9.90 mmol) in methanol (22 mL) was cooled to 0° C. and potassium carbonate (137 mg, 0.99 mmol) was added. The reaction mixture was allowed to warm and stir at rt for 10 min, during which time a yellow precipitate formed. The reaction mixture was then concentrated and diluted with ether (200 mL). The organic solution was washed with water (200 mL) and brine (200 mL), dried over MgSO4, filtered and concentrated to give 5-ethynyl-2-methyl-3-nitropyridine (1.48 g, 92%) as a solid. LCMS (FA): Rt=1.64 min, m/z=163.0 (M+H). | C#Cc1cnc(C)c([N+](=O)[O-])c1 | null | 92.2 | null |
1,447,008 | ord_dataset-a86112d52cd54525a5e36d41f18aced2 | null | 2014-01-01T00:07:00 | true | I[C:2]1[CH:13]=[CH:12][C:5]2[C:6]([CH2:9][CH2:10][NH2:11])=[CH:7][O:8][C:4]=2[CH:3]=1.OC1C=CC([I:25])=CC=1C(OC)=O>>[I:25][C:13]1[CH:2]=[CH:3][C:4]2[O:8][CH:7]=[C:6]([CH2:9][CH2:10][NH2:11])[C:5]=2[CH:12]=1 | NCCc1coc2cc(I)ccc12 | COC(=O)c1cc(I)ccc1O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Synthesized as described for 2-(6-iodo-1-benzofuran-3-yl)ethanamine using methyl 2-hydroxy-5-iodobenzoate. 1H-NMR (400 MHz, DMSO-d6): δ 2.91 (t, J=7.7 Hz, 2H), 3.11 (m, 2H), 7.45 (d, J=8.5 Hz, 1H), 7.65 (dd, J=8.5, 1.8 Hz, 1H), 7.90 (s, 1H), 8.09 (bs, 2H), 8.11 (d, J=1.7 Hz, 1H). | NCCc1coc2ccc(I)cc12 | null | null | null |
336,351 | ord_dataset-65c44df6676d4ce3a1874db5d7958ca9 | null | 1996-01-01T00:08:00 | true | [ClH:1].[CH3:2][O:3][C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:13]=1[C@@H:12]([CH2:14][OH:15])[C@@H:11]([NH:16][CH2:17][CH:18]=[CH2:19])[CH2:10][CH2:9]2.[H][H]>[Pd].C(O)C>[ClH:1].[CH3:2][O:3][C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:13]=1[C@@H:12]([CH2:14][OH:15])[C@@H:11]([NH:16][CH2:17][CH2:18][CH3:19])[CH2:10][CH2:9]2 | C=CCN[C@H]1CCc2cccc(OC)c2[C@H]1CO | [H][H] | null | [Pd] | Cl | 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 | 18 | The mixture of 0.99 g (4.0 mmol) of cis-(+-)-1,2,3,4-tetrahydro-8-methoxy-2-(2-propenylamino)-1-naphthalenemethanol hydrochloride, 0.5 g 10% Palladium on carbon, and 80 mL of 95% ethanol was shaken in a Parr shaker apparatus under 50 p.s.i. of hydrogen atmosphere. After 18 hours, the mixture was filtered through a Celite pad, concentrated in vacuo. The resulting oil was treated with excess HCl/MeOH and recrystallized from ethyl acetate/methanol to give pure title compound as a white solid: m.p. 233°-234° C. | CCCN[C@H]1CCc2cccc(OC)c2[C@H]1CO | null | null | null |
934,735 | ord_dataset-d8a5dc784dde4465894ec7c69d2e3ba6 | null | 2010-01-01T00:01:00 | true | [C:1]([O:5][C:6]([NH:8][C:9]1[CH:14]=[C:13]([O:15][C:16]2[CH:17]=[C:18]([CH2:22][CH2:23][C:24](O)=[O:25])[CH:19]=[CH:20][CH:21]=2)[CH:12]=[CH:11][N:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:27]([C:31]1[CH:32]=[C:33]([CH:35]=[CH:36][CH:37]=1)[NH2:34])([CH3:30])([CH3:29])[CH3:28].CCN=C=NCCCN(C)C>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:27]([C:31]1[CH:32]=[C:33]([NH:34][C:24](=[O:25])[CH2:23][CH2:22][C:18]2[CH:17]=[C:16]([CH:21]=[CH:20][CH:19]=2)[O:15][C:13]2[CH:12]=[CH:11][N:10]=[C:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:2])[CH3:3])[CH:14]=2)[CH:35]=[CH:36][CH:37]=1)([CH3:30])([CH3:28])[CH3:29] | CC(C)(C)OC(=O)Nc1cc(Oc2cccc(CCC(=O)O)c2)ccn1 | CC(C)(C)c1cccc(N)c1 | null | CCN=C=NCCCN(C)C | CN(C)c1ccncc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | null | 18 | To a solution of 3-[3-({2-[(tert-butoxycarbonyl)amino]pyridin-4-yl}oxy)phenyl]propanoic acid (333 mg, 0.93 mmol) in DCM (10 mL), were added 3-tert-butylaniline (152 mg, 1.02 mmol), DMAP (125 mg, 1.02 mmol) and then EDCI (196 mg, 1.02 mmol). The reaction was stirred for 18 h., and then diluted with DCM and washed with water and brine. The organic solution was dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography to yield the title compound as a white solid (389 mg, 86%). LCMS: (FA) ES+ 490.2 (M+1), ES− 488.2 (M−1). | CC(C)(C)OC(=O)Nc1cc(Oc2cccc(CCC(=O)Nc3cccc(C(C)(C)C)c3)c2)ccn1 | null | 85.4 | null |
72,374 | ord_dataset-520610070b3c4780a03b44c7fcecc28f | null | 1980-01-01T00:10:00 | true | [OH:1][C:2]1[C:11]2[CH2:10][CH2:9][CH2:8][CH2:7][C:6]=2[O:5][C:4](=[O:12])[C:3]=1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[O:19]1[CH2:24][CH2:23][N:22]([CH2:25][CH2:26][CH2:27]Cl)[CH2:21][CH2:20]1>>[O:19]1[CH2:24][CH2:23][N:22]([CH2:25][CH2:26][CH2:27][O:1][C:2]2[C:11]3[CH2:10][CH2:9][CH2:8][CH2:7][C:6]=3[O:5][C:4](=[O:12])[C:3]=2[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH2:21][CH2:20]1 | ClCCCN1CCOCC1 | O=c1oc2c(c(O)c1-c1ccccc1)CCCC2 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Obtained by causing the reaction, as indicated in Example 14, Stage B, of 14.5 g. (0.06 mol) of 4-hydroxy-3-phenyl-5,6,7,8-tetrahydrocoumarin with 15.6 g. (0.078 mol) of 3-morpholino-1-chloropropane. 10.1 g. of a paste which cannot be crystallised are isolated. Yield 45.7% (theoretical yield 22.1 g.). | O=c1oc2c(c(OCCCN3CCOCC3)c1-c1ccccc1)CCCC2 | null | 45.7 | null |
1,183,666 | ord_dataset-9cd817a75dfc4fe7ad19d4232772d5ff | null | 2012-01-01T00:07:00 | true | [O:1]1[C:5]2[CH2:6][NH:7][CH2:8][CH:9]([OH:10])[C:4]=2[CH:3]=[CH:2]1.F[C:12]1[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[CH:14][CH:13]=1>>[C:16]([C:15]1[CH:18]=[CH:19][C:12]([O:10][CH:9]2[CH2:8][NH:7][CH2:6][C:5]3[O:1][CH:2]=[CH:3][C:4]2=3)=[CH:13][CH:14]=1)#[N:17] | OC1CNCc2occc21 | N#Cc1ccc(F)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The same method as in Example 1 was conducted using 4,5,6,7-tetrahydrofuro[2,3-c]pyridin-4-ol (Reference Example 4) instead of 6-methyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-4-ol (Reference Example 6) and was conducted using 4-fluorobenzonitrile instead of 1-fluoronaphthalene to give the objective compound. | N#Cc1ccc(OC2CNCc3occc32)cc1 | null | null | null |
59,810 | ord_dataset-09e9a37ee5794dc28c0ad7bf7a442c18 | null | 1979-01-01T00:11:00 | true | Cl[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][N:3]=1.[F:11][C:12]([F:16])([F:15])[CH2:13][OH:14].[OH-].[Li+].CS(C)=O>O>[F:11][C:12]([F:16])([F:15])[CH2:13][O:14][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][N:3]=1 | OCC(F)(F)F | O=[N+]([O-])c1ccc(Cl)nc1 | null | [Li+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CS(C)=O | O | null | null | null | null | null | null | null | null | null | null | null | 2-Chloro-5-nitropyridine (9.5 grams), 2,2,2-trifluoroethanol (6.0 grams), and lithium hydroxide (4.0 grams) were mixed in 50 ml. of DMSO and stirred overnight (about 18 hours) at room temperature. The reaction mixture was then poured into water and the product was separated by filtration. It was crystallized from ethyl acetate-hexanes, yield 5.0 grams, m.p., 35°-37° C. | O=[N+]([O-])c1ccc(OCC(F)(F)F)nc1 | null | null | null |
1,377,161 | ord_dataset-d23f2f15886d4c22b7d7ba5f0e203e81 | null | 2013-01-01T00:12:00 | true | [NH2:1][C:2]1[C:7]([C:8]2[N:37]([C:38]3[CH:43]=[CH:42][C:41]([C:44]4([NH:48][C:49](=[O:55])[O:50][C:51]([CH3:54])([CH3:53])[CH3:52])[CH2:47][CH2:46][CH2:45]4)=[CH:40][CH:39]=3)[C:11]3=[N:12][C:13]([C:16]4[CH:21]=[CH:20][CH:19]=[C:18]([N:22]5[CH2:27][CH2:26][O:25][C@H:24]([CH2:28][O:29]CC6C=CC=CC=6)[CH2:23]5)[CH:17]=4)=[CH:14][CH:15]=[C:10]3[N:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1>CO.[Pd]>[NH2:1][C:2]1[C:7]([C:8]2[N:37]([C:38]3[CH:43]=[CH:42][C:41]([C:44]4([NH:48][C:49](=[O:55])[O:50][C:51]([CH3:53])([CH3:52])[CH3:54])[CH2:45][CH2:46][CH2:47]4)=[CH:40][CH:39]=3)[C:11]3=[N:12][C:13]([C:16]4[CH:21]=[CH:20][CH:19]=[C:18]([N:22]5[CH2:27][CH2:26][O:25][C@H:24]([CH2:28][OH:29])[CH2:23]5)[CH:17]=4)=[CH:14][CH:15]=[C:10]3[N:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1 | CC(C)(C)OC(=O)NC1(c2ccc(-n3c(-c4cccnc4N)nc4ccc(-c5cccc(N6CCO[C@H](COCc7ccccc7)C6)c5)nc43)cc2)CCC1 | 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 | 50 | 7.5 | 10% Pd/C (30 mg) was added to a solution of tert-butyl (1-{4-[2-(2-aminopyridin-3-yl)-5-(3-{(2S)-2-[(benzyloxy)methyl]morpholin-4-yl}phenyl)-3H-imidazo[4,5-b]pyridin-3-yl]phenyl}cyclobutyl)carbamate (36.0 mg, 0.0488 mmol) in MeOH (2 mL). The mixture was stirred at room temperature for 14 hours and 7.5 hours at 50° C. under hydrogen atmosphere. The catalyst was removed by filtration through a Celite pad and washed with MeOH. The combined filtrate and washings were concentrated. The residue was purified by PTLC (CHCl3/MeOH=9:1) to afford desired compound (4.6 mg, 14.6%) as pale yellow solid. | CC(C)(C)OC(=O)NC1(c2ccc(-n3c(-c4cccnc4N)nc4ccc(-c5cccc(N6CCO[C@H](CO)C6)c5)nc43)cc2)CCC1 | null | 14.6 | null |
412,519 | ord_dataset-fbdd058349aa456f812e3546c84baab5 | null | 1998-01-01T00:09:00 | true | [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][C:10]=1[CH2:16][CH2:17][CH2:18][C:19]1[CH:27]=[CH:26][C:22]([C:23]([OH:25])=[O:24])=[CH:21][CH:20]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:34](Br)[CH:35]=[CH2:36].O>CN(C=O)C>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:36][CH:35]=[CH2:34])=[CH:11][C:10]=1[CH2:16][CH2:17][CH2:18][C:19]1[CH:20]=[CH:21][C:22]([C:23]([OH:25])=[O:24])=[CH:26][CH:27]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1 | O=C(O)c1ccc(CCCc2cc(O)ccc2OCc2ccccc2)cc1 | C=CCBr | 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 | null | 18 | To a mixture of 4-[3-(2-benzyloxy-5-hydroxyphenyl)propyl]- benzoic acid (150 mg) (prepared as described in Example 4) and potassium carbonate (125 mg) in DMF (5 ml) was added allyl bromide (0.076 ml). The mixture was stirred for 18 hours, then potassium carbonate (125 mg) and allyl bromide (0.076 ml) were added and the mixture stirred for a further 18 hours. The mixture was poured into water (50 ml) and extracted with ethyl acetate (2×20 ml). The combined organics solutions were washed with brine (25 ml) and sodium bicarbonate (25 ml), dried (magnesium sulphate) filtered and evaporated. There was thus obtained allyl 4-[3-(2-benzyloxy-5-(allyloxy)phenyl)propyl]benzoate (150 mg). | C=CCOc1ccc(OCc2ccccc2)c(CCCc2ccc(C(=O)O)cc2)c1 | null | null | null |
137,023 | ord_dataset-a1d4c9f5edd844798727d514977ca73e | null | 1985-01-01T00:11:00 | true | [F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[NH2:12])[N:8]([CH2:13][CH3:14])[CH:7]=[C:6]([C:15]([OH:17])=[O:16])[C:5]2=[O:18].CO[C:21]1(OC)[CH2:25][CH2:24][CH2:23]O1>C(O)(=O)C>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[N:12]1[CH:21]=[CH:25][CH:24]=[CH:23]1)[N:8]([CH2:13][CH3:14])[CH:7]=[C:6]([C:15]([OH:17])=[O:16])[C:5]2=[O:18] | COC1(OC)CCCO1 | CCn1cc(C(=O)O)c(=O)c2cc(F)c(N)cc21 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(=O)O | null | null | null | null | null | null | null | null | null | null | null | null | 2.5 Grams of 6-fluoro-7-amino-1-ethyl-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid are suspended in 15 ml of acetic acid, and 1.32 gram of dimethoxytetrahydrofuran is added; the mixture is heated gradually until the solid dissolves, and is then allowed to cool. The precipitate formed is filtered off and washed with ethanol. The product is recrystallized in acetonitrile, and 1.4 gram of needles is obtained, of melting point 251°-252° C. | CCn1cc(C(=O)O)c(=O)c2cc(F)c(-n3cccc3)cc21 | null | null | null |
688,472 | ord_dataset-56747de2718a4ac5bf061651d1cc9e3e | null | 2005-01-01T00:10:00 | true | [O:1]1[C:5]2[CH:6]=[CH:7][C:8]([N:10]3[C:18]4[C:17]5[CH:19]=[C:20]([NH:23][C:24]([C:26]6[C:27]([NH:32]CC7C=CC(OC)=CC=7)=[N:28][CH:29]=[CH:30][CH:31]=6)=[O:25])[CH:21]=[CH:22][C:16]=5[CH2:15][CH2:14][C:13]=4[C:12]([C:42]([NH2:44])=[O:43])=[N:11]3)=[CH:9][C:4]=2[O:3][CH2:2]1.C(O)(C(F)(F)F)=O.C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl>[NH2:32][C:27]1[C:26]([C:24]([NH:23][C:20]2[CH:21]=[CH:22][C:16]3[CH2:15][CH2:14][C:13]4[C:12]([C:42]([NH2:44])=[O:43])=[N:11][N:10]([C:8]5[CH:7]=[CH:6][C:5]6[O:1][CH2:2][O:3][C:4]=6[CH:9]=5)[C:18]=4[C:17]=3[CH:19]=2)=[O:25])=[CH:31][CH:30]=[CH:29][N:28]=1 | COc1ccc(CNc2ncccc2C(=O)Nc2ccc3c(c2)-c2c(c(C(N)=O)nn2-c2ccc4c(c2)OCO4)CC3)cc1 | null | null | O=C([O-])[O-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | O=C(O)C(F)(F)F | null | null | null | null | null | null | null | null | null | null | null | The title compound of Example 209 (1.96 g, 0.0033 mol) was dissolved in 6 mL CH2Cl2 and reacted with 5 mL TFA at room temperature for 36 h. The crude reaction mixture was diluted with CH2Cl2 and basified with a saturated aqueous solution of Na2CO3. The layers were separated and the organic layer was dried over MgSO4. The residue obtained after removal of the solvent under vacuum was triturated with EtOH to afford 0.503 g of title compound (yield: 32%). Mp: 265-267° C. 1H NMR (300 MHz, d6-DMSO): δ 2.88-2.95 (m, 4H), 6.12 (s, 2H), 5.58-6.62 (dd, 1H, J=7.6 Hz, 4.7 Hz), 6.97-7.08 (m, 4H), 7.17 (d, 1H, J=1.9 Hz), 7.28 (s, 1H), 7.32 (s, 2H), 7.55 (s, 2H), 7.95-7.98 (dd, 1H, J=7.7 Hz, 1.7 Hz), 8.11-8.13 (dd, 1H, J=4.7 Hz, 1.7 Hz), 9.99 (s, 1H). M+1=469. | NC(=O)c1nn(-c2ccc3c(c2)OCO3)c2c1CCc1ccc(NC(=O)c3cccnc3N)cc1-2 | null | 32.5 | null |
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