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 ⌀ |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
243,716 | ord_dataset-fa3b512e2d924b9b965301ebcba6853d | null | 1992-01-01T00:03:00 | true | Cl.O.[NH:3]1[CH2:8][CH2:7][C:6](=[O:9])[CH2:5][CH2:4]1.C(=O)([O-])[O-].[Na+].[Na+].Cl[C:17]1[CH:22]=[CH:21][N:20]=[C:19]([C:23]([F:26])([F:25])[F:24])[N:18]=1>C(Cl)Cl>[F:24][C:23]([F:26])([F:25])[C:19]1[N:20]=[C:21]([N:3]2[CH2:8][CH2:7][C:6](=[O:9])[CH2:5][CH2:4]2)[CH:22]=[CH:17][N:18]=1 | O=C1CCNCC1 | FC(F)(F)c1nccc(Cl)n1 | null | Cl | O=C([O-])[O-] | [Na+] | 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 | 48 | 4-Piperidone monohydrate hydrochloride (XXVII, 3.37 g, 21.9 mmol) was added to a stirred mixture of methylene chloride (50 mL) and saturated aqueous sodium carbonate (8 mL). 4-Chloro-2-(trifluoromethyl)pyrimidine (IV, 4.0 g, 21.9 mmol) was then added to the mixture which was then stirred for 2 days. The organic layer was separated, dried over magnesium sulfate, and concentrated in vacuo to give the product as a white solid (4.9 g, 92%) which was used in the next step without further purification. | O=C1CCN(c2ccnc(C(F)(F)F)n2)CC1 | null | 91.2 | null |
1,486,609 | ord_dataset-c3c1091f873b4f40827973a6f1f9b685 | null | 2014-01-01T00:09:00 | true | Br[C:2]1[CH:3]=[C:4]([N:8]2[CH2:16][CH:15]3[CH2:17][N:11]4[CH2:12][CH:13]([CH2:18][CH:9]2[CH2:10]4)[CH2:14]3)[CH:5]=[N:6][CH:7]=1.[CH3:19][O:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([O:27][CH3:28])[C:22]=1B(O)O>>[CH3:19][O:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([O:27][CH3:28])[C:22]=1[C:2]1[CH:3]=[C:4]([N:8]2[CH2:16][CH:15]3[CH2:17][N:11]4[CH2:12][CH:13]([CH2:18][CH:9]2[CH2:10]4)[CH2:14]3)[CH:5]=[N:6][CH:7]=1 | COc1cccc(OC)c1B(O)O | Brc1cncc(N2CC3CC4CC2CN(C4)C3)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The title compound was prepared from the product of Example 65A and 2,6-dimethoxyphenylboronic acid according to General Method B: LC-MS Method D (ESI+) m/z 366.0 (M+H)+, retention time 1.34 minutes. | COc1cccc(OC)c1-c1cncc(N2CC3CC4CC2CN(C4)C3)c1 | null | null | null |
1,101,718 | ord_dataset-af85e6f81c2d49f08086afd6d9e6959c | null | 2011-01-01T00:10:00 | true | [CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:10]=[CH:11][C:12]3[N:16]=[CH:15][N:14]([C:17]4[S:18][C:19]([C:28](O)=[O:29])=[C:20]([C:22]5[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=5)[N:21]=4)[C:13]=3[CH:31]=2)[CH2:4][CH2:3]1.C[N:33](C(N(C)C)=[N+]1C2C(=NC=CC=2)N=N1)C.F[P-](F)(F)(F)(F)F.[Cl-].[NH4+].C(N(C(C)C)C(C)C)C>CN(C)C=O>[CH3:1][N:2]1[CH2:3][CH2:4][N:5]([CH2:8][C:9]2[CH:10]=[CH:11][C:12]3[N:16]=[CH:15][N:14]([C:17]4[S:18][C:19]([C:28]([NH2:33])=[O:29])=[C:20]([C:22]5[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=5)[N:21]=4)[C:13]=3[CH:31]=2)[CH2:6][CH2:7]1 | CN(C)C(N(C)C)=[N+]1N=Nc2ncccc21 | CN1CCN(Cc2ccc3ncn(-c4nc(-c5ccccc5)c(C(=O)O)s4)c3c2)CC1 | null | F[P-](F)(F)(F)(F)F | [Cl-] | [NH4+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(C(C)C)C(C)C | CN(C)C=O | null | null | null | null | null | null | null | null | null | 25 | 1 | To a mixture of 0.022 g (0.05 mmole) of 2-[6-(4-methyl-piperazin-1-ylmethyl)-benzoimidazol-1-yl]-4-phenyl-thiazole-5-carboxylic acid (I.1b), 0.023 g (0.06 mmole) of 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium, 3-oxide, hexafluorophosphate(1-) (1:1), 0.004 g of ammonium chloride and 1 mL of dimethylformamide was added 0.026 mL (0.15 mmole) of ethyldiisopropylamine. The mixture was stirred at ambient temperature for 1 hour. Solids were removed by filtration and the filtrate purified by reverse phase silica gel chromatography, eluting with acetonitrile-water (gradient 10:90-90:10) to give 0.014 g of 2-[6-(4-methyl-piperazin-1-ylmethyl)-benzoimidazol-1-yl]-4-phenyl-thiazole-5-carboxylic acid amide (I.1) as a white powder. MH+/Z=433. | CN1CCN(Cc2ccc3ncn(-c4nc(-c5ccccc5)c(C(N)=O)s4)c3c2)CC1 | null | 64.7 | null |
417,128 | ord_dataset-1cb9d78632144c5f8acfc3e9ff388678 | null | 1998-01-01T00:11:00 | true | [Br:1][C:2]1[C:6]([CH2:7]Br)=[CH:5][S:4][CH:3]=1.[C:9]([O-:12])(=[O:11])[CH3:10].[K+].O>CC(C)=O>[C:9]([O:12][CH2:7][C:6]1[C:2]([Br:1])=[CH:3][S:4][CH:5]=1)(=[O:11])[CH3:10] | CC(=O)[O-] | BrCc1cscc1Br | null | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CC(C)=O | null | null | null | null | null | null | null | null | null | 25 | 5 | A mixture of 3-bromo-4-methylthiophene (8.85 g), N-bromosuccinimide (8.85 g), 2,2'-azobis(isobutyronitrile) (0.16 g) and carbon tetrachloride (100 ml) was stirred under reflux for 6 hours. The mixture was concentrated under reduced pressure to give a crude product of 3-bromo-4-bromomethylthiophene. A suspension of this crude product of 3-bromo-4-bromomethylthiophene and potassium acetate (30 g) in acetone (100 ml) was stirred at room temperature for 5 hours. The mixture was poured into water and extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give a crude product of 4-acetoxymethyl-3-bromothiophene. This crude product was dissolved in tetrahydrofuran (50 ml), and 1N aqueous sodium hydroxide (50 ml) and ethanol (20 ml) were added. The mixture was stirred at room temperature for 2 hours and washed with diethyl ether. The aqueous layer was acidified with 1N hydrochloric acid and extracted with ethyl acetate. The extract was dried over anhdrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give 3-bromo-4-hydroxymethylthiophene (5.33 g) as oil. 3-Bromo-4-hydroxymethylthiophene was dissolved in methylene chloride (100 ml), and manganese dioxide (15 g) was added. The mixture was stirred at room temperature for 6 hours, and insoluble substances were removed by filtration. The filtrate was concentrated under reduced pressure to give a crude product of 4-bromo-3-thiophenecarbaldehyde. The crude product of 4-bromo-3-thiophenecarbaldehyde was dissolved in acetonitrile (50 ml), and sodium dihydrogen phosphate (1.2 g) in water (15 ml) and 30% aqueous hydrogen peroxide (3.5 ml) were added. Further, sodium chlorite (3.7 g) in water (40 ml) was added dropwise under ice-cooling. The mixture was stirred at room temperature for 2 hours, alkalified with 1N aqueous sodium hydroxide and washed with diethyl ether. The aqueous layer was acidified with 1N hydrochloric acid and extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give 4-bromo-3-thiophenecarboxylic acid (3.40 g) as crystals. | CC(=O)OCc1cscc1Br | null | null | null |
692,760 | ord_dataset-35824232b132464aa99e71aba765981d | null | 2005-01-01T00:12:00 | true | [Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[C:13]3=[CH:14][CH2:15][CH2:16][CH2:17][C:12]3([CH2:18][C:19]3[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][CH:20]=3)[NH:11][C:10]2=[O:27])[CH:5]=[C:6]([Cl:8])[CH:7]=1.[H-].[Na+].[CH3:30]I>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[C:13]3=[CH:14][CH2:15][CH2:16][CH2:17][C:12]3([CH2:18][C:19]3[CH:20]=[CH:21][C:22]([C:23]#[N:24])=[CH:25][CH:26]=3)[N:11]([CH3:30])[C:10]2=[O:27])[CH:5]=[C:6]([Cl:8])[CH:7]=1 | N#Cc1ccc(CC23CCCC=C2N(c2cc(Cl)cc(Cl)c2)C(=O)N3)cc1 | CI | 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 | 4-[1-(3,5-Dichlorophenyl)-2-oxo-1,2,3,4,5,6-hexahydro-benzimidazol-3a-ylmethyl]benzonitrile (200 mg) (0.5 mmol) in DMF (6 ml) was carefully dropped on a suspension of NaH 60% (24.1 mg) (1.2 eq) in DMF (5 ml) at RT. The reaction mixture was stirred 1 h at RT then methyl iodide (0.095 ml) (3 eq) was added. After one night, the reaction mixture was poured on water and extracted with tBuOMe. The organic layer was washed with water, dried over Na2SO4, and concentrated to yield a solid which was washed with diisopropyl ether to give 4-[1-(3,5-Dichlorophenyl)-3-methyl-2-oxo-1,2,3,4,5,6-hexahydro-benzimidazol-3a-ylmethyl]benzonitrile (115 mg) as a white solid. 1H NMR (CDCl3): 7.55 (2H, d), 7.25 (2H, d), 7.10 (1H, m), 6.75 (2H, m), 4.95 (1H, m), 3.10-3.0 (5H, m), 2.45-1.65 (6H, m). | CN1C(=O)N(c2cc(Cl)cc(Cl)c2)C2=CCCCC21Cc1ccc(C#N)cc1 | null | null | null |
190,875 | ord_dataset-d1bd8c96676b4d21aad27b173c6b4eff | null | 1989-01-01T00:06:00 | true | [CH3:1][N:2]([CH2:4][C:5]([OH:7])=O)[CH3:3].C(N1C=CN=C1)(N1C=CN=C1)=O.[NH2:20][CH2:21][CH2:22][N:23]1[C:27]([CH3:28])=[CH:26][CH:25]=[C:24]1[CH3:29]>COCCOC>[CH3:29][C:24]1[N:23]([CH2:22][CH2:21][NH:20][C:5](=[O:7])[CH2:4][N:2]([CH3:3])[CH3:1])[C:27]([CH3:28])=[CH:26][CH:25]=1 | CN(C)CC(=O)O | Cc1ccc(C)n1CCN | null | O=C(n1ccnc1)n1ccnc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | COCCOC | null | null | null | null | null | null | null | null | null | null | 25 | 5 | 5.2 g (0.05 mol) of N,N-dimethylaminoacetic acid and 8.1 g (0.05 mol) of carbonyldiimidazole in 20 ml of ethylene glycol dimethyl ether are stirred at 70° C. for 15 min. After addition of 5.5 g (0.04 mol) of 1-(2-aminoethyl)-2,5-dimethylpyrrole, dissolved in 20 ml of ethylene glycol dimethyl ether, to the mixture it is stirred at room temperature for 5 h, then concentrated, water is added, and the mixture is extracted first when acid and then when alkaline. The product contained in the extract from the mixture which has been made alkaline is crystallized using ligroin. Yield: 4.3 g (39% of theory), Melting point: 63°-65° C. Elemental analysis: C12H21N3O (223.32) calculated: C 64.5 H 9.5 N 18.8 O 7.2 found: C 64.0 H 9.4 N 18.5 O 8.0 | Cc1ccc(C)n1CCNC(=O)CN(C)C | null | null | null |
204,684 | ord_dataset-76a008eb2d3f48d891cad325041f3d1e | null | 1990-01-01T00:02:00 | true | C[O-].[Na+].[SH:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][N:6]=1.[NH2:11][C:12]1[N:17]=[C:16]([CH2:18]Cl)[CH:15]=[C:14]([O:20][CH3:21])[N:13]=1>CO.O>[NH2:11][C:12]1[N:13]=[C:14]([O:20][CH3:21])[CH:15]=[C:16]([CH2:18][S:4][C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][N:6]=2)[N:17]=1 | Sc1ccccn1 | COc1cc(CCl)nc(N)n1 | null | C[O-] | [Na+] | 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 | 18 g of 30% methanolic sodium methylate solution are added to a solution of 11.1 g of 2-mercaptopyridine in 100 ml of methanol, and stirring is then maintained at 20°-25° C. for 1 hours. To this solution are added portionwise 17.4 g of 2-amino-4-chloromethyl-6-methoxy-pyrimidine, and the mixture is stirred at 20°-25° C. for a further 2 hours. In further processing, the mixture is diluted with 1 liter of water, and the precipitating crystalline product is separated and dried. The yield is 22.5 g (91% of theory) of 2-amino-4-methoxy-6-(pyridin-2-yl-thiomethyl)-pyrimidine, m.p. 115°-116° C. | COc1cc(CSc2ccccn2)nc(N)n1 | null | null | null |
1,495,308 | ord_dataset-366bdd9ee72d474cbe6f3f9e54dd96d2 | null | 2014-01-01T00:10:00 | true | [C:1]([NH:9][C:10]1[N:18]=[CH:17][N:16]=[C:15]2[C:11]=1[N:12]=[CH:13][N:14]2[CH2:19][C:20]([O:22]CC)=[O:21])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+].Cl>O>[C:1]([NH:9][C:10]1[N:18]=[CH:17][N:16]=[C:15]2[C:11]=1[N:12]=[CH:13][N:14]2[CH2:19][C:20]([OH:22])=[O:21])(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1 | CCOC(=O)Cn1cnc2c(NC(=O)c3ccccc3)ncnc21 | null | null | Cl | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | null | null | null | null | null | null | null | null | null | null | 25 | 2 | Compound 9 (1.63 g, 5 mmol) and NaOH (0.4 g, 10 mmol) were dissolved in water (20 mL) and the solution was stirred for 2 h at room temperature. The pH was adjusted to 3 using 1M HCl, causing precipitation of the product. The precipitate was separated by filtration, washed with water, and dried in vacuo to give 4 as a white solid: yield 1.4 g (95%); MS(+ESI): m/z 298 [M+H]+; 1H NMR (400 MHz, d-DMSO): δ11.682 (s, 1H), 9.11 (s, 1H), 8.81 (s, 1H), 8.52 (s, 1H), 8.09 (d, 2H, J=7.2 Hz), 7.67 (t, 1H, J=7.2 Hz), 7.60 (t, 2H, J=7.2 Hz), 5.16 (s, 2H); 13C NMR (400 MHz, CDCl3): δ169.43, 166.34, 152.89, 152,09, 150.29, 145.63, 133.74, 132.98, 128.45, 122.56, 44.88. | O=C(O)Cn1cnc2c(NC(=O)c3ccccc3)ncnc21 | null | null | null |
495,209 | ord_dataset-9df8b3ec9c8742b3802e0efaac6f6ef3 | null | 2001-01-01T00:03:00 | true | [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][CH2:17][CH2:18][NH:19][CH2:20][CH2:21][C:22]2[C:30]3[C:25](=[CH:26][CH:27]=[C:28]([OH:31])[CH:29]=3)[NH:24][C:23]=2[C:32]2[CH:37]=[C:36]([CH3:38])[CH:35]=[C:34]([CH3:39])[CH:33]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:41]([O:43][CH2:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)=[O:42].C(N(C(C)C)CC)(C)C>>[CH2:44]([O:43][C:41](=[O:42])[N:19]([CH2:18][CH2:17][CH2:16][CH2:15][C:12]1[CH:11]=[CH:10][C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[CH:14][CH:13]=1)[CH2:20][CH2:21][C:22]1[C:30]2[C:25](=[CH:26][CH:27]=[C:28]([OH:31])[CH:29]=2)[NH:24][C:23]=1[C:32]1[CH:37]=[C:36]([CH3:38])[CH:35]=[C:34]([CH3:39])[CH:33]=1)[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1 | O=C(Cl)OCc1ccccc1 | Cc1cc(C)cc(-c2[nH]c3ccc(O)cc3c2CCNCCCCc2ccc(OCc3ccccc3)cc2)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(C(C)C)C(C)C | null | null | null | null | null | null | null | null | null | null | 25 | null | To a solution of 3-[2-[4-(4-benzyloxyphenyl)butylamino]ethyl]-2-(3,5-dimethylphenyl)-1H-indol-5-ol (234 mg in 5 mL of dry methylene chloride) at −78° C. was added benzyl chloroformate (0.082 mL) and diisopropylethylamine (0.104 mL) and the mixture stirred at room temperature. After 1 hour the reaction was quenched by the addition of saturated sodium bicarbonate and extracted with ethyl acetate. The organic portion was washed with saturated ammonium chloride, dried over magnesium sulfate and concentrated in vacuo. Purification by flash chromatography on silica gel (hexane:ethyl acetate, 3:1 then 2:1) gave the title compound (155 mg). | Cc1cc(C)cc(-c2[nH]c3ccc(O)cc3c2CCN(CCCCc2ccc(OCc3ccccc3)cc2)C(=O)OCc2ccccc2)c1 | null | null | null |
1,545,968 | ord_dataset-cac8df8aff894288876df4e093c9877f | null | 2015-01-01T00:02:00 | true | Br[C:2]1[S:3][C:4]2[CH:10]=[C:9]([CH2:11][N:12]3[C:16]4[CH:17]=[C:18]([O:23][CH3:24])[C:19]([O:21][CH3:22])=[CH:20][C:15]=4[N:14]=[CH:13]3)[CH:8]=[CH:7][C:5]=2[N:6]=1.[NH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[OH:32].CCN(C(C)C)C(C)C>CC(N(C)C)=O>[CH3:22][O:21][C:19]1[C:18]([O:23][CH3:24])=[CH:17][C:16]2[N:12]([CH2:11][C:9]3[CH:8]=[CH:7][C:5]4[N:6]=[C:2]([NH:25][C:26]5[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=5[OH:32])[S:3][C:4]=4[CH:10]=3)[CH:13]=[N:14][C:15]=2[CH:20]=1 | COc1cc2ncn(Cc3ccc4nc(Br)sc4c3)c2cc1OC | Nc1ccccc1O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(C(C)C)C(C)C | CC(=O)N(C)C | null | null | null | null | null | null | null | null | null | 110 | null | To a suspension of 2-bromo-6-((5,6-dimethoxy-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazole (70 mg, 0.17 mmol) from Example 2 and 2-aminophenol (95 mg, 0.87 mmol) in anhydrous DMA (300 μL) at rt was added DIEA (90 μL, 0.52 mmol). The mixture was stirred and heated in a sealed tube at 110° C. for 96 h. After cooling to rt, the mixture was purified by reverse-phase preparative HPLC using a mixture of water (5% CH3CN, 0.05% HCOOH) and CH3CN (0.05% HCOOH) as the mobile phase and Varian Pursuit XRs C18 column as the stationary phase to afford 2-((6-((5,6-dimethoxy-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)phenol (12 mg, 16%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 9.77 (br s, 1H), 8.14-8.26 (m, 2H), 7.75 (s, 1H), 7.49 (d, J=8.3 Hz, 1H), 7.24-7.29 (m, 1H), 7.16-7.22 (m, 2H), 6.79-6.92 (m, 3H), 5.46 (s, 2H), 3.76 (s, 6H). LCMS (ESI) m/z 461 (M+H)+. | COc1cc2ncn(Cc3ccc4nc(Nc5ccccc5O)sc4c3)c2cc1OC | null | 16.3 | null |
391,428 | ord_dataset-4bc8addcf9cf4845817557760d62d5b5 | null | 1998-01-01T00:02:00 | true | Cl[C:2]1[C:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:10][C:9]2[C:4](=[C:5]([O:20][CH3:21])[CH:6]=[CH:7][C:8]=2[O:18][CH3:19])[N:3]=1.C(O)(=[O:24])C>>[C:12]1([C:11]2[C:2](=[O:24])[NH:3][C:4]3[C:9]([CH:10]=2)=[C:8]([O:18][CH3:19])[CH:7]=[CH:6][C:5]=3[O:20][CH3:21])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1 | CC(=O)O | COc1ccc(OC)c2nc(Cl)c(-c3ccccc3)cc12 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | A solution of 2-chloro-3-phenyl-5,8-dimethoxyquinoline (200 mg, 0.67 mmol) was refluxed for 3 hours in acetic acid (1.5 ml) and water (0.05 ml.) After the solvent was evaporated, the residue was dissolved in water, basified with aqueous ammonium hydroxide 25% and extracted with chloroform (3×25 ml). The combined chloroform layers were dried over sodium sulfate and evaporated, yielding an essentially pure residue of 187 mg (100%) of 3-phenyl-5,8-dimethoxy-2-(1H)-quinolinone. m.p. 207 (CDCl3). | COc1ccc(OC)c2[nH]c(=O)c(-c3ccccc3)cc12 | null | 100 | null |
505,481 | ord_dataset-631d58dab387485c8eb0db4c20a232b7 | null | 2001-01-01T00:06:00 | true | [C:1]([CH2:3][CH2:4][O:5][C:6]([C:8]1[CH:13]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[C:16]([F:21])[CH:15]=2)[NH:12][C:11]([O:22][CH3:23])=[N:10][C:9]=1[CH2:24][O:25][CH3:26])=[O:7])#[N:2].Cl[C:28]([O:30][C:31]1[CH:36]=[CH:35][C:34]([N+:37]([O-:39])=[O:38])=[CH:33][CH:32]=1)=[O:29]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:1]([CH2:3][CH2:4][O:5][C:6]([C:8]1[CH:13]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[C:16]([F:21])[CH:15]=2)[N:12]([C:28]([O:30][C:31]2[CH:32]=[CH:33][C:34]([N+:37]([O-:39])=[O:38])=[CH:35][CH:36]=2)=[O:29])[C:11]([O:22][CH3:23])=[N:10][C:9]=1[CH2:24][O:25][CH3:26])=[O:7])#[N:2] | O=C(Cl)Oc1ccc([N+](=O)[O-])cc1 | COCC1=C(C(=O)OCCC#N)C(c2ccc(F)c(F)c2)NC(OC)=N1 | null | CN(C)c1ccncc1 | 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 well stirred solution of (+)-5-(2-cyanoethoxycarbonyl)-1,6-dihydro-2-methoxy-4-methoxymethyl-6-(3,4-difluorophenyl)pyrimidine (0.82 g, 2.24 mmol) and 4-(N,N-dimethylamino)pyridine (0.329 g, 2.69 mmol) in CH2Cl2 (200 mL) was added a powder of 4-nitrophenyl chloroformate (0.543 g, 2.69 mmol) at room temperature. The solvent was evaporated and the residue was purified by column chromatography on silica gel using dichloromethane/hexane (20%-50%) as the eluent to give (+)-5-(2-cyanoethoxycarbonyl)-4-methoxymethyl-1,6-dihydro-2-methoxy-6-(3,4-difluorophenyl)-1-[(4-nitrophenyloxy)carbonyl]pyrimidine (0.80 g, 67%) as a viscous oil. | COCC1=C(C(=O)OCCC#N)C(c2ccc(F)c(F)c2)N(C(=O)Oc2ccc([N+](=O)[O-])cc2)C(OC)=N1 | null | 67.3 | null |
1,093,191 | ord_dataset-52a37d876ddb453e86de0c15fa233d29 | null | 2011-01-01T00:09:00 | true | [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11]1[NH:15][C:14]([CH:16]([CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][C:25](=[O:28])[CH2:26][CH3:27])[C:17]([OH:19])=[O:18])=[N:13][CH:12]=1.[H-].[Na+].[CH3:31][Si:32]([CH2:35][CH2:36][O:37][CH2:38]Cl)([CH3:34])[CH3:33]>C1COCC1>[CH2:26]([C:25]1([CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH:16]([C:14]2[N:15]([CH2:38][O:37][CH2:36][CH2:35][Si:32]([CH3:34])([CH3:33])[CH3:31])[C:11]([C:2]3[CH:3]=[CH:4][C:5]4[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=4)[CH:1]=3)=[CH:12][N:13]=2)[C:17]([O:19][C:2]([CH3:11])([CH3:3])[CH3:1])=[O:18])[O:18][CH2:17][CH2:16][O:28]1)[CH3:27] | CCC(=O)CCCCCC(C(=O)O)c1ncc(-c2ccc3ccccc3c2)[nH]1 | C[Si](C)(C)CCOCCl | null | [H-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | 25 | 1 | To a solution of Example 1, A3 in dry THF (0.06 M solution) at 0° C. was added NaH (60%, 1.5 eq.) portionwise, the resulting mixture was stirred for 1 hr and then SEM-Cl (1.5 eq.) was added dropwise. The solution was allowed to warm to RT and stirred for a further 3 hrs. The reaction was quenched by the addition of sat. aq. NH4Cl solution and the mixture extracted with EtOAc. The organic layer was washed with brine, dried (Na2SO4) and concentrated under reduced pressure. The crude was purified by column chromatography on silica gel eluting with 20-50% EtOAc/petroleum ether to obtain D1 as a pale brown foam. 1H NMR (400 MHz, CDCl3) δ: 8.32 (1H, s), 7.91-7.75 (5H, m), 7.49-7.37 (2H, m), 5.43 (1H, d, J=10.9 Hz), 5.26 (1H, d, J=10.9 Hz), 3.90 (4H, s), 3.86 (2H, t, J=7.4 Hz), 3.57 (1H, t, J=8.1 Hz), 2.27-2.14 (2H, m), 1.67-1.57 (4H, m), 1.49 (9H, s), 1.41-1.27 (6H, m), 0.96 (2H, t, J=7.4 Hz), 0.87 (3H, t, J=7.5 Hz), 0.07 (9H, s). MS (ES) C35H52N2O5Si requires: 608, found: 609 (M+H)+. | CCC1(CCCCCC(C(=O)OC(C)(C)C)c2ncc(-c3ccc4ccccc4c3)n2COCC[Si](C)(C)C)OCCO1 | null | null | null |
1,256,832 | ord_dataset-266f60b4555945d6afb2d2bdf5fa04e0 | null | 2013-01-01T00:02:00 | true | [C:1]([O:5][C:6](=[O:23])[NH:7][CH:8]([C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[C:17]([Cl:22])[CH:16]=1)[C:9](=[O:14])N(OC)C)([CH3:4])([CH3:3])[CH3:2].Br[C:25]1[CH:37]=[CH:36][C:28]([O:29][CH2:30][C:31]2([CH3:35])[CH2:34][O:33][CH2:32]2)=[CH:27][C:26]=1[F:38]>>[C:1]([O:5][C:6](=[O:23])[NH:7][CH:8]([C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[C:17]([Cl:22])[CH:16]=1)[C:9]([C:25]1[CH:37]=[CH:36][C:28]([O:29][CH2:30][C:31]2([CH3:35])[CH2:34][O:33][CH2:32]2)=[CH:27][C:26]=1[F:38])=[O:14])([CH3:2])([CH3:3])[CH3:4] | CON(C)C(=O)C(NC(=O)OC(C)(C)C)c1ccc(Cl)c(Cl)c1 | CC1(COc2ccc(Br)c(F)c2)COC1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The title compound was prepared from rac-[(3,4-dichloro-phenyl)-(methoxy-methyl-carbamoyl)-methyl]-carbamic acid tert-butyl ester (Intermediate 9) and 3-(4-bromo-3-fluoro-phenoxymethyl)-3-methyl-oxetane (Intermediate 32) in analogy to Example 1a): MS (ISP): 498.3 and 500.2 (M+H)+, 398.2 and 400.0 ((M-Boc)+H)+ (100%); MS (ISN): 496.4 and 498.5 (M−H)−. | CC1(COc2ccc(C(=O)C(NC(=O)OC(C)(C)C)c3ccc(Cl)c(Cl)c3)c(F)c2)COC1 | null | null | null |
1,644,442 | ord_dataset-bcc0b01d4f58457a8733b10a099f43ba | null | 2015-01-01T00:10:00 | true | [OH:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][C:9]2=[O:12])=[CH:4][CH:3]=1.[Br:13][CH2:14][CH2:15][CH2:16][CH2:17]Br.C([O-])([O-])=O.[K+].[K+]>CCO.O>[Br:13][CH2:14][CH2:15][CH2:16][CH2:17][O:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][C:9]2=[O:12])=[CH:4][CH:3]=1 | BrCCCCBr | O=C1NCCc2ccc(O)cc21 | null | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CCO | null | null | null | null | null | null | null | null | null | null | 8 | A mixture of intermediate 19 (196 mg, 1.2 mmol), 1,4-dibromobutane (0.43 mL, 3.6 mmol) and anhydrous K2CO3 (166 mg, 1.22 mmol) was dissolved in EtOH (4 mL) and the solution was heated to reflux and stirred overnight. The mixture was diluted with water and extracted with EtOAc. The combined EtOAc layers were washed with water, brine, dried over anhydrous Na2SO4, concentrated in vacuo and purified by flash chromatography on silica gel column (elution with PE/EtOAc=3:1) to give 7-(4-bromobutoxy)-3,4-dihydroisoquinolin-1(2H)-one (intermediate 21) (230 mg, 63%) as a white solid. | O=C1NCCc2ccc(OCCCCBr)cc21 | null | 64.3 | null |
1,062,294 | ord_dataset-ffbef48837674f39816de887b5dc8bae | null | 2011-01-01T00:06:00 | true | [C:1]1([CH2:7][O:8][C:9]2[CH:17]=[CH:16][CH:15]=[C:14]3[C:10]=2[CH:11]=[N:12][NH:13]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:18][C:19]1[CH:20]=[C:21](B(O)O)[CH:22]=[CH:23][C:24]=1[O:25][CH3:26].N1C=CC=CC=1>C(Cl)Cl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH3:18][C:19]1[CH:20]=[C:21]([N:13]2[C:14]3[C:10](=[C:9]([O:8][CH2:7][C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[CH:17]=[CH:16][CH:15]=3)[CH:11]=[N:12]2)[CH:22]=[CH:23][C:24]=1[O:25][CH3:26] | c1ccc(COc2cccc3[nH]ncc23)cc1 | COc1ccc(B(O)O)cc1C | null | [Cu+2] | CC(=O)[O-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | c1ccncc1 | null | null | null | null | null | null | null | null | null | null | null | The 4-[(phenylmethyl)oxy]-1H-indazole (D1) (500 mg, 2.23 mmol), the [3-methyl-4-(methyloxy)phenyl]boronic acid (740 mg, 4.46 mmol), copper (II) acetate (608 mg, 3.345 mmol), pyridine (0.36 mL, 4.46 mmol) and powdered molecular sieves (400 mg) in DCM (75 mL) were stirred at room temperature in the presence of air. After 41 hours the mixture was filtered through a pad of celite and washed with water. The aqueous was re-extracted with DCM and the combined organics were washed with brine and dried over MgSO4. The crude (1.17 g) was purified by flash chromatography (Biotage SP4) with a gradient of EtOAc 0 to 30% in hexane to afford 562 mg of title compound (D34) containing an impurity. | COc1ccc(-n2ncc3c(OCc4ccccc4)cccc32)cc1C | null | 73.2 | null |
27,721 | ord_dataset-14866e68bb5b47f5929457eecb4eb3a5 | null | 1977-01-01T00:07:00 | true | [OH:1][C:2]1[C:3]2[C:4](=[N:16][N:17]([CH3:19])[CH:18]=2)[N:5]=[CH:6][C:7]=1[C:8]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:9].CI.[C:22](=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[C:8]([C:7]1[C:2](=[O:1])[C:3]2[C:4](=[N:16][N:17]([CH3:19])[CH:18]=2)[N:5]([CH3:22])[CH:6]=1)(=[O:9])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1 | Cn1cc2c(O)c(C(=O)c3ccccc3)cnc2n1 | O=C([O-])[O-] | null | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | CI | null | null | null | null | null | null | null | null | null | null | null | 25.3 g. of (4-hydroxy-2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)phenylmethanone (0.1 mol.), 15.5 g. of methyl iodide (0.11 mol.) and 21 g. of potassium carbonate (0.15 mol.) are heated in 150 ml. of dimethylformamide with stirring at 80° for 10 hours. After this time, the inorganic precipitate is filtered off and the filtrate evaporated to dryness. The remaining 5-benzoyl-2,7-dihydro-2,7-dimethyl-4H-pyrazolo[3,4-b]pyridin-4-one is recrystallized from butanol, yield 18 g. (67%); m.p. 272°-274°. | Cn1cc2c(=O)c(C(=O)c3ccccc3)cn(C)c2n1 | null | null | null |
1,153,917 | ord_dataset-b195433d5c354ddfb6cde0d53c41910f | null | 2012-01-01T00:04:00 | true | [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]3[CH:22]=[CH:21][C:20]([C:23]([O:25][CH3:26])=[O:24])=[CH:19][CH:18]=3)=[O:15])[CH2:10][CH:9]2[CH2:27][NH:28][C@@H:29]([C:31]2[C:40]3[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=3)[CH:34]=[CH:33][CH:32]=2)[CH3:30])=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:48](=O)([O:54]C(C)(C)C)[O:49][C:50]([CH3:53])([CH3:52])[CH3:51]>ClCCl>[C:50]([O:49][C:48]([N:28]([CH2:27][CH:9]1[CH:8]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]2[CH:18]=[CH:19][C:20]([C:23]([O:25][CH3:26])=[O:24])=[CH:21][CH:22]=2)=[O:15])[CH2:10]1)[C@@H:29]([C:31]1[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH:34]=[CH:33][CH:32]=1)[CH3:30])=[O:54])([CH3:53])([CH3:52])[CH3:51] | CC(C)(C)OC(=O)OC(C)(C)C | COC(=O)c1ccc(OC(=O)N2CCC(c3ccc(F)cc3)C(CN[C@H](C)c3cccc4ccccc34)C2)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | CCN(CC)CC | null | null | null | null | null | null | null | null | null | 25 | 37 | To a solution of 888 mg of 4-(methoxycarbonyl)phenyl 4-(4-fluorophenyl)-3-({[(1R)-1-(1-naphthyl)ethyl]amino}methyl)piperidine-1-carboxylate in 9 mL of dichloromethane were added 0.7 mL of triethylamine and 868 mg of di-tert-butyl carbonate, followed by stirring at room temperature for 37 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel chromatography (hexane-ethyl acetate) to obtain 503 mg of 4-(methoxycarbonyl)phenyl 3-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate as a pale yellow foamy substance. | COC(=O)c1ccc(OC(=O)N2CCC(c3ccc(F)cc3)C(CN(C(=O)OC(C)(C)C)[C@H](C)c3cccc4ccccc34)C2)cc1 | null | 47.8 | null |
588,323 | ord_dataset-7a74d48eeefd45aba53e7258f3ae067a | null | 2003-01-01T00:04:00 | true | [CH2:1]([N:3]([CH2:8][CH3:9])[CH2:4][CH2:5][CH2:6][NH2:7])[CH3:2].[C:10]([C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([CH2:21][CH2:22][NH:23][C:24](=[O:38])[C:25]3[CH:30]=[CH:29][C:28]([C:31]4[CH:36]=[CH:35][N:34]=[C:33](Cl)[N:32]=4)=[CH:27][CH:26]=3)[CH:19]=2)[NH:14][CH:13]=1)#[N:11]>>[C:10]([C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([CH2:21][CH2:22][NH:23][C:24](=[O:38])[C:25]3[CH:30]=[CH:29][C:28]([C:31]4[CH:36]=[CH:35][N:34]=[C:33]([NH:7][CH2:6][CH2:5][CH2:4][N:3]([CH2:8][CH3:9])[CH2:1][CH3:2])[N:32]=4)=[CH:27][CH:26]=3)[CH:19]=2)[NH:14][CH:13]=1)#[N:11] | N#Cc1c[nH]c2ccc(CCNC(=O)c3ccc(-c4ccnc(Cl)n4)cc3)cc12 | CCN(CC)CCCN | null | null | null | null | null | null | null | 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 3-(diethylamino)-propylamine and N-[2-(3-Cyano-1H-indol-5-yl)-ethyl]-4-[2-chloro-pyrimidin-4-yl]-benzamide (reference example 1az) as substrates. | CCN(CC)CCCNc1nccc(-c2ccc(C(=O)NCCc3ccc4[nH]cc(C#N)c4c3)cc2)n1 | null | null | null |
1,286,157 | ord_dataset-d5c54236ecd94d61aaa071461bcfc426 | null | 2013-01-01T00:04:00 | true | [CH3:1][O:2][C:3](=[O:25])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][C:13]=2[CH2:22][NH:23][CH3:24])[CH:6]=1.[F:26][C:27]([F:39])([F:38])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[S:34](Cl)(=[O:36])=[O:35]>>[CH3:1][O:2][C:3](=[O:25])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:20])([F:19])[F:21])=[CH:14][C:13]=2[CH2:22][N:23]([CH3:24])[S:34]([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=2[C:27]([F:26])([F:38])[F:39])(=[O:36])=[O:35])[CH:6]=1 | CNCc1cc(C(F)(F)F)ccc1Oc1cccc(CC(=O)OC)c1 | O=S(=O)(Cl)c1ccccc1C(F)(F)F | null | null | null | null | null | null | null | 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 22, Step 1, using the following starting materials: [3-(2-methylaminomethyl-4-trifluoromethyl-phenoxy)-phenyl]-acetic acid methyl ester and 2-(trifluoromethyl)benzenesulfonyl chloride. | COC(=O)Cc1cccc(Oc2ccc(C(F)(F)F)cc2CN(C)S(=O)(=O)c2ccccc2C(F)(F)F)c1 | null | null | null |
1,673,595 | ord_dataset-9cc455db05a444779921f786a45b21a6 | null | 2015-01-01T00:12:00 | true | [I-].[CH3:2][S+](C)(C)=O.[H-].[Na+].[F:9][C:10]1[CH:15]=[CH:14][C:13](/[CH:16]=[CH:17]/[C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:12][CH:11]=1.O>CS(C)=O>[F:9][C:10]1[CH:11]=[CH:12][C:13]([C@@H:16]2[CH2:2][C@H:17]2[C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:14][CH:15]=1 | C[S+](C)(C)=O | CCOC(=O)/C=C/c1ccc(F)cc1 | null | [H-] | [I-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CS(C)=O | null | null | null | null | null | null | null | null | null | 25 | 1 | Trimethylsulfoxonium iodide (7.92 g, 36.0 mmol) in dimethyl sulfoxide (40 mL) was mixed with sodium hydride (55 wt % dispersion in mineral oil, 1.57 g, 36.0 mmol) under cooling with ice, stirred at room temperature for 1 hour and then stirred with (E)-ethyl 3-(4-fluorophenyl)acrylate (5.83 g, 30.0 mmol) for 18 hours. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1) to give the title compound as a colorless oil (793 mg, yield 13%). | CCOC(=O)[C@@H]1C[C@H]1c1ccc(F)cc1 | null | 12.7 | null |
719,327 | ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa | null | 2006-01-01T00:07:00 | true | [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[N:22]([CH2:23][CH:24]=[C:25]([CH3:27])[CH3:26])[C:21]3[C:20](=[O:28])[N:19]([CH2:29][O:30][C:31](=[O:36])[C:32]([CH3:35])([CH3:34])[CH3:33])[C:18](=[O:37])[NH:17][C:16]=3[N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].Br[CH2:45][C:46]([O:48][CH2:49][CH3:50])=[O:47]>CN(C)C=O.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[N:22]([CH2:23][CH:24]=[C:25]([CH3:26])[CH3:27])[C:21]3[C:20](=[O:28])[N:19]([CH2:29][O:30][C:31](=[O:36])[C:32]([CH3:35])([CH3:34])[CH3:33])[C:18](=[O:37])[N:17]([CH2:45][C:46]([O:48][CH2:49][CH3:50])=[O:47])[C:16]=3[N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4] | CCOC(=O)CBr | CC(C)=CCn1c(N2CCN(C(=O)OC(C)(C)C)CC2)nc2[nH]c(=O)n(COC(=O)C(C)(C)C)c(=O)c21 | null | O=C([O-])[O-] | [K+] | 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 | 13 | 4-[1-(2,2-Dimethylpropionyloxymethyl)-7-(3-methylbut-2-enyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl]piperazine-1-carboxylic acid tert-butyl ester (43 mg) and potassium carbonate (13 mg) were suspended in N,N-dimethylformamide (1 ml), and ethyl bromoacetate (9.6 μl) was added to the suspension. After the reaction mixture was stirred at room temperature for 13 hours, the mixture was diluted with ethyl acetate, washed with water, and dried over anhydrous magnesium sulfate. The solvent was removed by distillation from the organic layer to give 44 mg of the title compound. δ: 1.19 (s, 9H) 1.23–1.51 (m, 3H) 1.48 (s, 9H) 1.74 (s, 6H) 3.14–3.20 (m, 4H) 3.52–3.58 (m, 4H) 4.17–4.27 (m, 2H) 4.68–4.72 (m, 2H) 4.75 (s, 2H) 5.37–5.42 (m, 1H) 6.03 (s, 2H) | CCOC(=O)Cn1c(=O)n(COC(=O)C(C)(C)C)c(=O)c2c1nc(N1CCN(C(=O)OC(C)(C)C)CC1)n2CC=C(C)C | null | null | null |
518,600 | ord_dataset-a495451286334c5c9bbcbd48a00c1350 | null | 2001-01-01T00:09:00 | true | [OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:20])[N:7]([CH2:12][O:13][C:14](=[O:19])[C:15]([CH3:18])([CH3:17])[CH3:16])[CH:8]=[N:9]2)=[CH:4][CH:3]=1.O[CH2:22][CH2:23][CH2:24][N:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C(Cl)Cl>[O:28]1[CH2:29][CH2:30][N:25]([CH2:24][CH2:23][CH2:22][O:1][C:2]2[CH:11]=[C:10]3[C:5]([C:6](=[O:20])[N:7]([CH2:12][O:13][C:14](=[O:19])[C:15]([CH3:16])([CH3:17])[CH3:18])[CH:8]=[N:9]3)=[CH:4][CH:3]=2)[CH2:26][CH2:27]1 | CC(C)(C)C(=O)OCn1cnc2cc(O)ccc2c1=O | OCCCN1CCOCC1 | null | CCOC(=O)N=NC(=O)OCC | c1ccc(P(c2ccccc2)c2ccccc2)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | null | 0.08 | 7-Hydroxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (750 mg, 2.7 mmol) was suspended in methylene chloride (40 ml) at 5° C. and 4-(3-hydroxypropyl)morpholine (490 mg, 3.4 mmol) and triphenylphosphine (890 mg, 3.4 mmol) were added. The mixture was stirred for 5 minutes and diethyl azodicarboxylate (590 mg, 3.4 mmol) was added over 5 minutes at 5° C. The reaction mixture was stirred at 5° C. for 30 minutes then at ambient temperature for 1 hour. The solution was then purified directly by column flash chromatography eluting with methylene chloride, and then ethyl acetate, acetonitrile/ethyl acetate (20/80), and acetonitrile/ethyl acetate/ammonia (50/50/0.5). The purified product was triturated with ether/isohexane and collected by filtration to give 7-(3-morpholinopropoxy)-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin4-one (745 mg, 68%). | CC(C)(C)C(=O)OCn1cnc2cc(OCCCN3CCOCC3)ccc2c1=O | null | 68.4 | null |
1,662,851 | ord_dataset-42cd9bc5aae3485f9a58f1527bd3abf0 | null | 2015-01-01T00:11:00 | true | [Cl:1][C:2]1[C:3]2[N:4]([C:22]([CH3:25])=[N:23][CH:24]=2)[C:5]([C:14]2[CH:19]=[C:18]([F:20])[CH:17]=[C:16]([F:21])[CH:15]=2)=[C:6]([C:8](N(OC)C)=[O:9])[CH:7]=1.Cl[Mg][CH2:28][CH3:29]>>[Cl:1][C:2]1[C:3]2[N:4]([C:22]([CH3:25])=[N:23][CH:24]=2)[C:5]([C:14]2[CH:15]=[C:16]([F:21])[CH:17]=[C:18]([F:20])[CH:19]=2)=[C:6]([C:8](=[O:9])[CH2:28][CH3:29])[CH:7]=1 | CC[Mg]Cl | CON(C)C(=O)c1cc(Cl)c2cnc(C)n2c1-c1cc(F)cc(F)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The desired compound was prepared by the procedure of Example 1, step J using 8-chloro-5-(3,5-difluorophenyl)-N-methoxy-N,3-dimethylimidazo[1,5-a]pyridine-6-carboxamide and chloro(ethyl)magnesium as the starting materials in 39% yield. LCMS calculated for C17H14ClF2N2O (M+H)+: m/z=335.1. found: 334.9. | CCC(=O)c1cc(Cl)c2cnc(C)n2c1-c1cc(F)cc(F)c1 | null | 39 | null |
980,065 | ord_dataset-35b56288528641309a040cc2b6710b61 | null | 2010-01-01T00:08:00 | true | [CH3:1][O:2][C:3](=[O:14])[C:4]1[CH:9]=[C:8]([N+:10]([O-:12])=[O:11])[C:7](Cl)=[N:6][CH:5]=1.Cl.[CH2:16]([O:23][C:24]1[CH:30]=[CH:29][C:27]([NH2:28])=[CH:26][CH:25]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.CCN(C(C)C)C(C)C>CO>[CH3:1][O:2][C:3](=[O:14])[C:4]1[CH:9]=[C:8]([N+:10]([O-:12])=[O:11])[C:7]([NH:28][C:27]2[CH:26]=[CH:25][C:24]([O:23][CH2:16][C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)=[CH:30][CH:29]=2)=[N:6][CH:5]=1 | Nc1ccc(OCc2ccccc2)cc1 | COC(=O)c1cnc(Cl)c([N+](=O)[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 | CO | null | null | null | null | null | null | null | null | null | 25 | 8 | To a solution of 6-chloro-5-nitro-nicotinic acid methyl ester (216 mg, 1.0 mmol) and 4-benzyloxyaniline hydrochloride (280 mg, 1.2 mmol) in MeOH (10 mL) was added iPr2NEt (0.35 mL, 2.0 mmol). The resulting mixture was stirred at rt overnight, a red solid precipitated from the mixture, which was collected by filtration. MS (ES, Pos.): m/z 380 [MH+]. 1H NMR (CDCl3, 400 MHz): δ=3.94 (s, 3H), 5.10 (s, 2H), 7.03 (d, J=8.8 Hz, 2H), 7.38-7.46 (m, 5H), 7.50 (d, J=8.8 Hz, 2H), 9.01 (d, J=2.0 Hz, 1H), 9.08 (d, J=2.0 Hz, 1H), 10.2 (br s, 1H). | COC(=O)c1cnc(Nc2ccc(OCc3ccccc3)cc2)c([N+](=O)[O-])c1 | null | null | null |
1,733,468 | ord_dataset-eacfee6d16d8455a93348409f1b37be4 | null | 2016-01-01T00:06:00 | true | [Cl:1][C:2]1[CH:3]=[C:4]([CH:31]=[CH:32][C:33]=1[O:34][CH3:35])[CH2:5][NH:6][C:7]1[C:12]([C:13]([NH:15][CH2:16][CH2:17][N:18]2[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]2)=[O:14])=[CH:11][N:10]=[C:9]([N:24]2[CH2:30][CH2:29][C:26]3([CH2:28][CH2:27]3)[CH2:25]2)[N:8]=1.C=O.[BH4-].[Na+].[CH2:40](Cl)Cl>CO>[Cl:1][C:2]1[CH:3]=[C:4]([CH:31]=[CH:32][C:33]=1[O:34][CH3:35])[CH2:5][NH:6][C:7]1[C:12]([C:13]([NH:15][CH2:16][CH2:17][N:18]2[CH2:19][CH2:20][N:21]([CH3:40])[CH2:22][CH2:23]2)=[O:14])=[CH:11][N:10]=[C:9]([N:24]2[CH2:30][CH2:29][C:26]3([CH2:27][CH2:28]3)[CH2:25]2)[N:8]=1 | ClCCl | COc1ccc(CNc2nc(N3CCC4(CC4)C3)ncc2C(=O)NCCN2CCNCC2)cc1Cl | null | C=O | [BH4-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | null | 1 | In methanol (10 mL) was dissolved 4-((3-chloro-4-methoxybenzyl)amino)-N-(2-(piperazin-1-yl)ethyl)-2-(5-azaspiro[2.4]heptan-5-yl)pyrimidine-5-formamide (250 mg, 0.5 mmol). Formalin (37%, 61 mg, 0.75 mmol) was added. The reaction was conducted at ambient temperature for 1 h. Sodium borohydride (28 mg, 0.75 mmol) was added. The reaction was continued for 8 h, followed by addition of DCM (50 mL). The reaction mixture was washed with water for three times (50 mL at a time). The organic phase was dried and concentrated to give 4-((3-chloro-4-methoxybenzyl)amino)-N-[2-(4-methylpiperazin-1-yl)ethyl]-2-(5-azaspiro[2.4]heptan-5-yl)pyrimidine-5-formamide (168 mg, 65% yield). The product was dissolved in methanol (5 mL). Hydrochloric acid (0.1 mL) was added. The reaction mixture was stirred at ambient temperature for 30 min. The solvent was removed by evaporation to give the hydrochloride salt of the compound as a white solid. | COc1ccc(CNc2nc(N3CCC4(CC4)C3)ncc2C(=O)NCCN2CCN(C)CC2)cc1Cl | null | 65 | null |
1,357,851 | ord_dataset-d932d1d683704a8bad3d064bcb197acc | null | 2013-01-01T00:11:00 | true | [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[N:11]2[CH:12]=[CH:13][CH:14]=[N:15][C:10]2=[N:9][C:8]=1[CH:16]([NH2:18])[CH3:17].[NH2:19][C:20]1[C:25]([C:26]#[N:27])=[C:24](Cl)[N:23]=[CH:22][N:21]=1.CCN(C(C)C)C(C)C>C(O)CCC>[NH2:19][C:20]1[C:25]([C:26]#[N:27])=[C:24]([NH:18][CH:16]([C:8]2[N:9]=[C:10]3[N:15]=[CH:14][CH:13]=[CH:12][N:11]3[C:7]=2[C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)[CH3:17])[N:23]=[CH:22][N:21]=1 | N#Cc1c(N)ncnc1Cl | CC(N)c1nc2ncccn2c1-c1ccccn1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCCCO | CCN(C(C)C)C(C)C | null | null | null | null | null | null | null | null | null | 100 | 8 | To a mixture of 1-(3-pyridin-2-yl-imidazo[1,2-a]pyrimidin-2-yl)-ethylamine (800 mg, 3.34 mmol) and 4-amino-6-chloro-pyrimidine-5-carbonitrile (520 mg 3.34 mmol) in n-butanol (5 mL) was added DIEA (1.7 mL, 10.04 mmol) at rt. The reaction mixture was stirred at 100° C. overnight. The mixture was concentrated in vacuo. The residue was purified by column chromatography using silica gel (100-200 mesh) and 0-30% acetone in hexane to provide 4-amino-6-[1-(3-pyridin-2-yl-imidazo[1,2-a]pyrimidin-2-yl)-ethylamino]-pyrimidine-5-carbonitrile: 1H NMR: (DMSO-d6, 400 MHz) δ 1.547 (d, J=6.4 Hz, 3H), 5.807-5.841 (br s, 1H), 7.150-7.176 (m, 1H), 7.289 (br s, 2H), 7.429-7.466 (m, 2H), 7.847-7.867 (m, 1H), 7.998 (s, 2H), 8.653 (s, 1H), 8.789 (s, 1H), 9.419 (d, J=6.4 Hz, 1H); LC-MS (ESI) m/z 358.2 [M+H]+. | CC(Nc1ncnc(N)c1C#N)c1nc2ncccn2c1-c1ccccn1 | null | null | null |
833,570 | ord_dataset-ec576c604a9d47258c87c732a043ec71 | null | 2008-01-01T00:08:00 | true | [NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]2[CH:17]=[CH:16][C:15]3[C:14]([C:18]([NH:20][CH2:21][CH:22]4[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]4)=[O:19])=[C:13]([Cl:28])[CH:12]=[CH:11][C:10]=3[N:9]=2)[CH2:3]1.[Si:29]([O:36][CH2:37][CH:38]=O)([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[Cl:28][C:13]1[CH:12]=[CH:11][C:10]2[N:9]=[C:8]([N:4]3[CH2:5][CH2:6][CH2:7][C@H:2]([NH:1][CH2:38][CH2:37][O:36][Si:29]([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30])[CH2:3]3)[CH:17]=[CH:16][C:15]=2[C:14]=1[C:18]([NH:20][CH2:21][CH:22]1[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]1)=[O:19] | N[C@H]1CCCN(c2ccc3c(C(=O)NCC4CCCCC4)c(Cl)ccc3n2)C1 | CC(C)(C)[Si](C)(C)OCC=O | null | CC(=O)O[BH-](OC(C)=O)OC(C)=O | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | null | null | Prepared according to the method of example 50(a) using 2-[(3S)-3-amino-1-piperidinyl]-6-chloro-N-(cyclohexylmethyl)-5-quinolinecarboxamide Example 51) (200 mg), activated 3 Å molecular sieves (0.20 g), (tert-butyldimethylsilyloxy)acetaldehyde (0.085 mL), dichloromethane (5.0 mL) and sodium triacetoxyborohydride (210 mg). Purification (SiO2, ethyl acetate:isohexane 1:1) gave the sub-titled compound (190 mg). | CC(C)(C)[Si](C)(C)OCCN[C@H]1CCCN(c2ccc3c(C(=O)NCC4CCCCC4)c(Cl)ccc3n2)C1 | null | null | null |
709,864 | ord_dataset-c8069773c1a148aca8ab417108daacc5 | null | 2006-01-01T00:05:00 | true | N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.[Cl:17][C:18]1[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][C:19]=1[NH:20][C:21]1[C:30]2[C:25](=[CH:26][C:27]([O:32][CH3:33])=[CH:28][C:29]=2[OH:31])[N:24]=[CH:23][N:22]=1.O[CH2:41][CH2:42][CH2:43][N:44]1[CH2:49][CH2:48][O:47][CH2:46][CH2:45]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[Cl:17][C:18]1[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][C:19]=1[NH:20][C:21]1[C:30]2[C:25](=[CH:26][C:27]([O:32][CH3:33])=[CH:28][C:29]=2[O:31][CH2:41][CH2:42][CH2:43][N:44]2[CH2:49][CH2:48][O:47][CH2:46][CH2:45]2)[N:24]=[CH:23][N:22]=1 | OCCCN1CCOCC1 | COc1ccc(Cl)c(Nc2ncnc3cc(OC)cc(O)c23)c1 | null | CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C | c1ccc(P(c2ccccc2)c2ccccc2)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | 25 | 1 | Di-tert-butyl azodicarboxylate (0.208 g) was added dropwise to a stirred mixture of 4-(2-chloro-5-methoxyanilino)-5-hydroxy-7-methoxyquinazoline (0.2 g), 4-(3-hydroxypropyl)morpholine (Bull. Soc. Chim. Fr., 1962, 1117; 0.131 g), triphenylphosphine (0.237 g) and methylene chloride (3 ml). The reaction mixture was stirred at ambient temperature for 1 hour. The mixture was evaporated and the residue was purified by column chromatography on silica using a 99:1 mixture of methylene chloride and a saturated methanolic ammonia solution as eluent. The material so obtained was triturated under diethyl ether. The resultant solid was isolated, washed with diethyl ether and dried under vacuum to give the title compound (0.12 g); NMR Spectrum: (DMSOd6 and CF3COOD) 2.35 (m, 2H), 3.1 (t, 2H), 3.3 (t, 2H), 3.5 (d, 2H), 3.68 (t, 2H), 3.8 (s, 3H), 4.0 (d, 2H), 4.02 (s, 3H), 4.6 (t, 2H), 6.93 (s, 1H), 7.05–7.15 (m, 2H), 7.5 (s, 1H), 7.57 (d, 1H), 8.87 (s, 1H); Mass Spectrum: M+H+ 459 and 461; Elemental Analysis: Found C, 60.0; H, 6.0; N, 12.1; C23H27ClN4O4 requires C, 60.19; H, 5.93; N, 12.2%. | COc1ccc(Cl)c(Nc2ncnc3cc(OC)cc(OCCCN4CCOCC4)c23)c1 | null | 43.4 | null |
1,102,535 | ord_dataset-375a420ee9b042918ddca20f02df37d3 | null | 2011-01-01T00:11:00 | true | Cl.[CH3:2][C:3]1[O:7][C:6]([C:8]2[CH:9]=[C:10]([CH3:14])[CH:11]=[CH:12][CH:13]=2)=[N:5][C:4]=1[CH2:15][O:16][C@H:17]1[CH2:22][CH2:21][CH2:20][C@@H:19]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[B:31]2[O:35]C(C)(C)C(C)(C)[O:32]2)[CH2:18]1>C1COCC1>[CH3:2][C:3]1[O:7][C:6]([C:8]2[CH:9]=[C:10]([CH3:14])[CH:11]=[CH:12][CH:13]=2)=[N:5][C:4]=1[CH2:15][O:16][C@H:17]1[CH2:22][CH2:21][CH2:20][C@@H:19]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[B:31]([OH:32])[OH:35])[CH2:18]1 | Cc1cccc(-c2nc(CO[C@H]3CCC[C@@H](OCc4ccccc4B4OC(C)(C)C(C)(C)O4)C3)c(C)o2)c1 | null | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | 25 | null | 1 ml of 1 N HCl is added to 300 mg of (1S,3R)-5-methyl-4-{3-[2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)benzyloxy]cyclohexyloxymethyl}-2-m-tolyloxazole in 5 ml of THF, and the mixture is stirred at RT until the reaction has gone to completion. The solvent is removed under reduced pressure and the compound is purified by RP-HPLC. This gives (1R,3S)-2-[3-(5-methyl-2-m-tolyloxazol-4-ylmethoxy)cyclohexyloxymethyl]benzeneboronic acid as a colorless oil. C25H30BNO5 (435.33), MS (ESI): 436 (M+H+). | Cc1cccc(-c2nc(CO[C@H]3CCC[C@@H](OCc4ccccc4B(O)O)C3)c(C)o2)c1 | null | null | null |
464,316 | ord_dataset-6c36eb0f817d4144988b8963c5d58879 | null | 2000-01-01T00:05:00 | true | [H-].[Na+].[O:3]=[C:4]1[CH2:8][CH2:7][CH2:6][CH:5]1[C:9]([O:11][CH3:12])=[O:10].C([Li])CCC.Br[CH2:19][CH2:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>C1COCC1.O>[O:3]=[C:4]1[C:8](=[CH:19][CH2:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:7][CH2:6][CH:5]1[C:9]([O:11][CH3:12])=[O:10] | COC(=O)C1CCCC1=O | BrCCCc1ccccc1 | null | [H-] | [Li]CCCC | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | O | null | null | null | null | null | null | null | null | null | 25 | 0.33 | To a suspension of 60% NaH (1.2 g, 30 mmol) in anhydrous THF (30 mL) in an ice bath is added a solution of methyl 2-oxocyclopentanecarboxylate (4.26 g, 30 mmol) in 10 mL of THF dropwise over 5 minutes. The mixture is stirred at room temperature for 20 minutes. The mixture is cooled to -25° C. and 2.5 M n-butyllithium is added over 5 minutes (12 mL, 30 mmol). After stirring for 5 minutes, 1-bromo-3-phenylpropane (4.6 mL, 30 mmol) is added. The mixture is stirred at room temperature for 3 hours. The mixture is poured into water and is extracted with ether. The organic layer is washed with water and is dried over MgSO4. The solvent is removed in vacuo and the residue is chromatographed on silica gel (6:1 hexane:ethyl acetate) to afford methyl 2-oxo-3-(3-phenylpropyl-1-yl)cyclopentanecarboxylate (1 g, 13%): 1H-NMR (300 MHz, CDCl3) δ (TMS) 1.22-1.50 (m, 2H), 1.62-1.90 (m, 4H), 2.12-2.38 (m, 4H), 2.58-2.69 (m, 2H), 3.75 (s, 3H), 7.10-7.32 (m, 5H); MS (EI) m/e 260 (M+). | COC(=O)C1CCC(=CCCc2ccccc2)C1=O | null | 12.9 | null |
1,370,423 | ord_dataset-d23f2f15886d4c22b7d7ba5f0e203e81 | null | 2013-01-01T00:12:00 | true | Cl[C:2]1[N:7]=[CH:6][C:5]([S:8]([N:11]2[CH2:20][CH2:19][C:18]3[C@:13]([CH2:31][O:32][CH3:33])([CH2:14][C:15]4[CH:23]=[N:22][N:21]([C:24]5[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=5)[C:16]=4[CH:17]=3)[CH2:12]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.Cl.[C@H:44]12[CH2:50][C@H:47]([NH:48][CH2:49]1)[CH2:46][O:45]2>>[F:30][C:27]1[CH:28]=[CH:29][C:24]([N:21]2[C:16]3[CH:17]=[C:18]4[C@:13]([CH2:31][O:32][CH3:33])([CH2:14][C:15]=3[CH:23]=[N:22]2)[CH2:12][N:11]([S:8]([C:5]2[CH:6]=[N:7][C:2]([N:48]3[CH2:49][C@@H:44]5[CH2:50][C@H:47]3[CH2:46][O:45]5)=[CH:3][CH:4]=2)(=[O:10])=[O:9])[CH2:20][CH2:19]4)=[CH:25][CH:26]=1 | COC[C@]12Cc3cnn(-c4ccc(F)cc4)c3C=C1CCN(S(=O)(=O)c1ccc(Cl)nc1)C2 | C1O[C@@H]2CN[C@H]1C2 | 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 | null | null | null | null | null | null | null | null | null | null | null | null | The title compound was prepared by the method of Example 20 using (R)-6-(6-chloropyridine-3-sulfonyl)-4a-methoxymethyl-1-(4-fluorophenyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triazacyclopenta[b]naphthalene, diisopropylethylamine and (1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptane hydrochloride. LCMS (Method F): 552 (M+H)+, Retention time 4.7 minutes. | COC[C@]12Cc3cnn(-c4ccc(F)cc4)c3C=C1CCN(S(=O)(=O)c1ccc(N3C[C@@H]4C[C@H]3CO4)nc1)C2 | null | null | null |
1,373,188 | ord_dataset-d23f2f15886d4c22b7d7ba5f0e203e81 | null | 2013-01-01T00:12:00 | true | [Br:1][C:2]1[C:10]2[C:9](Cl)=[N:8][CH:7]=[N:6][C:5]=2[N:4]([CH:12]2[CH2:15][O:14][CH2:13]2)[CH:3]=1.[OH-].[NH4+:17]>>[Br:1][C:2]1[C:10]2[C:9]([NH2:17])=[N:8][CH:7]=[N:6][C:5]=2[N:4]([CH:12]2[CH2:15][O:14][CH2:13]2)[CH:3]=1 | Clc1ncnc2c1c(Br)cn2C1COC1 | [NH4+] | null | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | 85 | null | To 5-bromo-4-chloro-7-(3-oxetanyl)-7H-pyrrolo[2,3-d]pyrimidine (185 mg, 0.641 mmol) was added ammonium hydroxide (24.97 μl, 0.641 mmol) in a 25 ml sealable vial and heated at 85° C. over 24 hr. The solid was isolated by filtration and washed with water (5 mL) and dried to give 5-bromo-7-(3-oxetanyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (106 mg), which was used without further purification. | Nc1ncnc2c1c(Br)cn2C1COC1 | null | 61.5 | null |
458,982 | ord_dataset-2501595af7f242268dbaab34c9e7ae56 | null | 2000-01-01T00:02:00 | true | [CH2:1]([O:3][CH:4]([O:32][CH2:33][CH3:34])[CH2:5][N:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]([CH2:27][C:28](O)=[O:29])([NH:15][C:16]([NH:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([O:25][CH3:26])[CH:20]=2)=[O:17])[C:7]1=[O:31])[CH3:2].Cl.C(N=C=NCCCN(C)C)C.[NH2:47][C:48]1[CH:53]=[CH:52][C:51]([CH3:54])=[CH:50][CH:49]=1>ClCCl.C(OCC)(=O)C>[CH2:33]([O:32][CH:4]([O:3][CH2:1][CH3:2])[CH2:5][N:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]([CH2:27][C:28]([NH:47][C:48]2[CH:53]=[CH:52][C:51]([CH3:54])=[CH:50][CH:49]=2)=[O:29])([NH:15][C:16]([NH:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([O:25][CH3:26])[CH:20]=2)=[O:17])[C:7]1=[O:31])[CH3:34] | CCOC(CN1C(=O)C(CC(=O)O)(NC(=O)Nc2cccc(OC)c2)c2ccccc21)OCC | Cc1ccc(N)cc1 | null | CCN=C=NCCCN(C)C | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | CCOC(C)=O | null | null | null | null | null | null | null | null | null | null | 9 | In 30 ml of dichloromethane was dissolved 0.50 g of (-)-1-(2,2-diethoxyethyl)-3-hydroxycarbonylmethyl-3-(N'-(3-methoxyphenyl)ureido)indolin-2-one, and 0.22 g of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride and 0.20 g of p-toluidine were successively added thereto. After stirring the mixture for 9 hours, the reaction mixture was diluted with ethyl acetate and washed successively with dilute hydrochloric acid and saturated aqueous sodium hydrogencarbonate. The organic layer was dried over anhydrous sodium sulfate and concentrated. The crude product was purified by silica gel column chromatography (hexane/ethyl acetate=2/1) to give 0.46 g of the title compound as a white powder. Because the compound is an enantiomer of the compound of Example 188, the NMR data are the same as those of the latter compound. | CCOC(CN1C(=O)C(CC(=O)Nc2ccc(C)cc2)(NC(=O)Nc2cccc(OC)c2)c2ccccc21)OCC | null | 77.4 | null |
1,188,443 | ord_dataset-9cd817a75dfc4fe7ad19d4232772d5ff | null | 2012-01-01T00:07:00 | true | C([O:4][C:5]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][C:6]=1[F:14])C=C.C(N(CC)[C:18]1[CH:23]=CC=C[CH:19]=1)C>>[CH2:23]([C:10]1[CH:9]=[C:8]([N+:11]([O-:13])=[O:12])[CH:7]=[C:6]([F:14])[C:5]=1[OH:4])[CH:18]=[CH2:19] | CCN(CC)c1ccccc1 | C=CCOc1ccc([N+](=O)[O-])cc1F | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Compound 2 (25 g, 126.8 mmol) was solved in diethyl aniline (150 mL, 937.7 mmol) and the resulting solution was refluxed for 48 h. The crude was evaporated in vacuo and the residue was purified by column chromatography, eluted at 10% ethyl acetate/hexane. Fractions were collected to obtain the desired compound 3 (15 g, yield 60%). | C=CCc1cc([N+](=O)[O-])cc(F)c1O | null | 60 | null |
832,881 | ord_dataset-ec576c604a9d47258c87c732a043ec71 | null | 2008-01-01T00:08:00 | true | [CH3:1][CH2:2][CH2:3]C(OC1C=CC([N+]([O-])=O)=CC=1)=O.[CH3:16][C@@H:17]([C@@H:29]1[C@@:33]2([CH3:50])[C@@H:34](O)[CH2:35][C@@H:36]3[C@@:41]4([CH3:47])[CH2:42][CH2:43][C@@H:44]([OH:46])[CH2:45][C@H:40]4[CH2:39][C@@H:38](O)[C@H:37]3[C@@H:32]2[CH2:31][CH2:30]1)[CH2:18][CH2:19][C:20](NCCS([O-])(=O)=O)=O.[Na+].[Na]>>[CH3:1][CH:2]([CH2:20][CH2:19][CH2:18][C@H:17]([C@@H:29]1[C@:33]2([CH3:50])[C@H:32]([C@H:37]3[C@H:36]([CH2:35][CH2:34]2)[C@:41]2([CH3:47])[C:40]([CH2:45][C@H:44]([CH2:43][CH2:42]2)[OH:46])=[CH:39][CH2:38]3)[CH2:31][CH2:30]1)[CH3:16])[CH3:3] | CCCC(=O)Oc1ccc([N+](=O)[O-])cc1 | C[C@H](CCC(=O)NCCS(=O)(=O)[O-])[C@H]1CC[C@H]2[C@@H]3[C@H](O)C[C@@H]4C[C@H](O)CC[C@]4(C)[C@H]3C[C@H](O)[C@]12C | null | [Na+] | [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 | The assay substrate contained p-Nitrophenyl butyrate (Sigma Cat. No. N9876) MW 209.2. Density 1.2 and Taurocholic acid, sodium salt (Sigma Cat. No. T 4009) MW 537.7 The assay substrate was prepared by dissolving 43 mg Taurocholic acid (6 mM final concentration)+87 μl p-Nitrophenyl butyrate (40 μM final concentration)+50 μl 20% Triton X-100 (0.08% final concentration) in 10 ml of 100 mM MOPS 2 mM CaCl2 pH 7.3. The substrate was shaken to dissolve the ingredients and centrifuged to clarify. | CC(C)CCC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C | null | null | null |
1,403,638 | ord_dataset-7456bda2326f4bebaa874a5474d4cc0d | null | 2014-01-01T00:03:00 | true | [F:1][C:2]1([F:26])[CH:8]([NH:9][C:10](=[O:15])[C:11]([F:14])([F:13])[F:12])[CH2:7][CH2:6][N:5](C(OCC2C=CC=CC=2)=O)[CH2:4][CH2:3]1>CO.[Pd]>[F:26][C:2]1([F:1])[CH2:3][CH2:4][NH:5][CH2:6][CH2:7][CH:8]1[NH:9][C:10](=[O:15])[C:11]([F:13])([F:14])[F:12] | O=C(OCc1ccccc1)N1CCC(NC(=O)C(F)(F)F)C(F)(F)CC1 | null | null | [Pd] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | null | null | Dess Martin periodinane (2.3 g, 5.4 mmol) was added portionwise to a solution of benzyl 4-azido-5-hydroxyazepane-1-carboxylate (1.3 g, 4.5 mmol) in DCM (25 mL). After stirring at room temperature for 18 hr, the mixture was diluted with DCM and quenched with aqueous NaHCO3 (40 mL) followed by aqueous Na2S2O3 (20%, 40 mL). The resulting mixture was stirred for 20 min. The organic layer was separated, dried over Na2SO4 and the solvent removed under reduced pressure. Purification via silica gel column chromatography (0-50% EtOAc/isohexane) gave benzyl 4-azido-5-oxoazepane-1-carboxylate (1.10 g, 84%) as a clear oil. To a solution of this oil (1.10 g, 3.8 mmol) in DCM (10 mL) was added deoxo-Fluor® (50% in THF, 3.5 mL, 9.5 mmol) and the mixture was stirred at room temperature for 18 hr. The mixture was diluted with DCM, cooled in an ice/water bath and quenched by dropwise addition of saturated aqueous NaHCO3 (20 mL). Effervescence was observed. The resulting mixture was stirred for 10 min. The organic layer was separated, dried over Na2SO4 and the solvent removed under reduced pressure. The crude product was purified via silica gel column chromatography (0-40% EtOAc/isohexane) to give benzyl 5-azido-4,4-difluoroazepane-1-carboxylate (0.65 g, 56%) as a clear oil. This oil was dissolved in THF (10 mL) and water (2 mL) and triphenylphosphine (0.58 g, 2.2 mmol) added. After stirring and heating at 60° C. for 18 hr, the mixture was concentrated under reduced pressure. The crude product was dissolved in DCM and the organic layer was washed with water, separated, dried over Na2SO4 and the solvent removed under reduced pressure. To the crude product in DCM (20 mL), cooled in a water/ice bath, was added DIPEA (1.1 mL, 6.36 mmol) followed by trifluoroacetic anhydride (0.75 mL, 5.3 mmol) dropwise. The mixture was allowed to warm to room temperature, stirred for 18 hr and diluted with DCM. Water was added and the organic layer was separated, dried over Na2SO4 and the solvent was removed under reduced pressure. The residue was purified via silica gel column chromatography (0-60% EtOAc/isohexane) to yield benzyl 4,4-difluoro5-(2,2,2-trifluoroacetamido)azepane-1-carboxylate (0.59 g, 73%) as a clear oil. This trifluoroacetamide (0.57 g, 1.5 mmol) was dissolved in MeOH (50 mL) and passed through the H-Cube® (Full H2 Mode, 70° C., flow rate: 1 mL/min, 30 mm 10% Pd/C cartridge). The solvent was removed under reduced pressure to give crude N-(5,5-difluoroazepan-4-yl)-2,2,2-trifluoroacetamide. To a solution of the azepane (0.37 g, 1.5 mmol) in EtOH (4 mL) was added 5-chloro-1-methyl-4-nitro-1H-pyrazole (0.73 g, 4.5 mmol) and DIPEA (0.65 mL, 3.8 mmol). The mixture was heated at 130° C. in a microwave for 6 hr. The solvent was removed under reduced pressure and the crude product was purified via silica gel column chromatography (0-50% EtOAc/isohexane) to yield N-(5,5-difluoro-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepan-4-yl)-2,2,2-trifluoroacetamide as a pale yellow oil (0.31 g, 56%). 1H NMR (400 MHz, CDCl3) δ 8.05 (s, 1H), 6.77 (d, J=9.0 Hz, 1H), 4.72-4.58 (m, 1H), 3.80 (s, 3H), 3.55-3.39 (m, 2H), 3.33-3.18 (m, 2H), 2.52-2.17 (m, 3H), 2.14-2.04 (m, 1H). | O=C(NC1CCNCCC1(F)F)C(F)(F)F | null | null | null |
569,870 | ord_dataset-5e1b2445a3d94ea592ddf2c284118a1e | null | 2002-01-01T00:11:00 | true | [CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([C:11]2[C:12](=[O:26])[NH:13][C:14](=[O:25])[C:15]=2[C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([N+:22]([O-])=O)[CH:17]=2)=[CH:3]1.[OH-].[Na+]>CC(C)=O>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([C:11]2[C:12](=[O:26])[NH:13][C:14](=[O:25])[C:15]=2[C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([NH2:22])[CH:17]=2)=[CH:3]1 | Cn1cc(C2=C(c3cccc([N+](=O)[O-])c3)C(=O)NC2=O)c2ccccc21 | null | null | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(C)=O | null | null | null | null | null | null | null | null | null | null | 25 | 8 | To a solution of 3-(1-methylindol-3-yl)-4-(3-nitrophenyl)-1H-pyrrole-2,5-dione (6.5 g, 19 mmol) in acetone (500 mL), was added TiCl3 (45 mL) in 5 portions at 30 minute interval. The reaction mixture was stirred at room temperature overnight and then neuteralized with 10N NaOH. The product was extracted with EtOAc, dried, and concentrated. The crude product was purified on a silica gel column with 3% MeOH in CH2Cl2 to afford 3-(1-methylindol-3-yl)-4-(3-aminophenyl)-1H-pyrrole-2,5-dione (4.9 g, 82.5%). | Cn1cc(C2=C(c3cccc(N)c3)C(=O)NC2=O)c2ccccc21 | null | 81.3 | null |
962,352 | ord_dataset-ed65749688da45af8a8432967b017729 | null | 2010-01-01T00:05:00 | true | Cl[C:2]1[C:3](=[O:18])[N:4]([CH:15]([CH3:17])[CH3:16])[S:5](=[O:14])(=[O:13])[C:6]=1[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[N:19]1[CH:24]=[CH:23][CH:22]=[C:21]([CH2:25][CH2:26][NH2:27])[CH:20]=1>>[CH:15]([N:4]1[C:3](=[O:18])[C:2]([NH:27][CH2:26][CH2:25][C:21]2[CH:20]=[N:19][CH:24]=[CH:23][CH:22]=2)=[C:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[S:5]1(=[O:14])=[O:13])([CH3:17])[CH3:16] | NCCc1cccnc1 | CC(C)N1C(=O)C(Cl)=C(c2ccccc2)S1(=O)=O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The title compound was prepared from 4-chloro-2-isopropyl-5-phenylisothiazol-3(2H)-one 1,1-dioxide and (2-pyridin-3-ylethyl)amine in a similar manner as described for Example 118. 1H NMR (500 MHz CDCl3): δ 1.59 (d, 6H), 2.59 (t, 2H), 3.17 (q, 2H), 4.37-4.45 (m, 1H), 5.47 (t, 1H), 7.06-7.09 (m, 1H), 7.14-7.17 (m, 1H), 7.46-7.55 (m, 5H), 8.07 (s, 1H), 8.44-8.46 (m, 1H); 13C NMR (125 MHz CDCl3): δ 20.38, 33.39, 44.78, 47.88, 107.76, 123.70, 125.15, 129.13, 130.20, 131.84, 133.02, 135.16, 136.13, 148.57, 150.06, 158.61; Mass Spectrum: M+H+ 372. | CC(C)N1C(=O)C(NCCc2cccnc2)=C(c2ccccc2)S1(=O)=O | null | null | null |
1,301,469 | ord_dataset-78c3f723155a4347a902b53bcee1524d | null | 2013-01-01T00:06:00 | true | [CH2:1]([O:8][C:9]1[CH:48]=[CH:47][C:12]([CH2:13][C@H:14]([NH:35][C:36](=[O:46])[O:37][C@H:38]2[C@H:45]3[C@H:41]([O:42][CH2:43][CH2:44]3)[O:40][CH2:39]2)[C@H:15]([OH:34])[CH2:16][N:17]([CH2:30][CH:31]([CH3:33])[CH3:32])[S:18]([C:21]2[CH:26]=[CH:25][C:24]([N+:27]([O-:29])=[O:28])=[CH:23][CH:22]=2)(=[O:20])=[O:19])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CO[C:51](OC)([CH3:53])[CH3:52].C1(C)C=CC(S(O)(=O)=O)=CC=1>ClCCl>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:13][C@H:14]2[C@@H:15]([CH2:16][N:17]([CH2:30][CH:31]([CH3:33])[CH3:32])[S:18]([C:21]3[CH:22]=[CH:23][C:24]([N+:27]([O-:29])=[O:28])=[CH:25][CH:26]=3)(=[O:19])=[O:20])[O:34][C:51]([CH3:53])([CH3:52])[N:35]2[C:36]([O:37][C@H:38]2[C@H:45]3[C@H:41]([O:42][CH2:43][CH2:44]3)[O:40][CH2:39]2)=[O:46])=[CH:47][CH:48]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1 | CC(C)CN(C[C@@H](O)[C@H](Cc1ccc(OCc2ccccc2)cc1)NC(=O)O[C@@H]1CO[C@H]2OCC[C@H]21)S(=O)(=O)c1ccc([N+](=O)[O-])cc1 | COC(C)(C)OC | null | Cc1ccc(S(=O)(=O)O)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 solution of (3S,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-1-[4-(benzyloxy)benzyl]-2-hydroxy-3-{isobutyl[(4-nitrophenyl)sulfonyl]amino}propylcarbamate (1.00 g, 1.5 mmol) in 20 mL of dichloromethane was added 2,2-dimethoxypropane (1.5 g, 14.6 mmol) and p-toluenesulfonic acid (0.09 g, 0.5 mmol). The solution was refluxed for 12 hours, and the solvent was removed under reduced pressure. The residue was purified on silica gel using ethyl acetate-hexanes (3.5:6.5) as eluent to provide 0.70 g (70%) of the title compound. | CC(C)CN(C[C@H]1OC(C)(C)N(C(=O)O[C@@H]2CO[C@H]3OCC[C@H]32)[C@H]1Cc1ccc(OCc2ccccc2)cc1)S(=O)(=O)c1ccc([N+](=O)[O-])cc1 | null | 64.5 | null |
1,495,034 | ord_dataset-366bdd9ee72d474cbe6f3f9e54dd96d2 | null | 2014-01-01T00:10:00 | true | [C:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N:11]1[CH2:16][CH2:15][N:14]([C:17](=[O:27])[C:18]([NH:20][CH:21]2[CH2:26][CH2:25][S:24][CH2:23][CH2:22]2)=[O:19])[CH2:13][CH2:12]1)([CH3:4])([CH3:3])[CH3:2].ClC1C=CC=C(C(OO)=[O:36])C=1.C([O-])(O)=O.[Na+]>C(OCC)(=O)C>[C:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N:11]1[CH2:12][CH2:13][N:14]([C:17](=[O:27])[C:18]([NH:20][CH:21]2[CH2:22][CH2:23][S:24](=[O:36])[CH2:25][CH2:26]2)=[O:19])[CH2:15][CH2:16]1)([CH3:4])([CH3:2])[CH3:3] | O=C(OO)c1cccc(Cl)c1 | CC(C)(C)c1ccccc1N1CCN(C(=O)C(=O)NC2CCSCC2)CC1 | null | O=C([O-])O | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOC(C)=O | null | null | null | null | null | null | null | null | null | null | 0 | 3 | To a solution of 2-[4-(2-tert-butylphenyl)piperazin-1-yl]-2-oxo-N-(tetrahydro-2H-thiopyran-4-yl)acetamide (Example 193, 0.25 g, 0.63 mmol), in ethyl acetate (5 mL) was added m-chloroperbenzoic acid (0.19 g, 0.76 mmol) at 0° C. After stirred at 0° C. for 3 h, the mixture was poured into saturated NaHCO3 solution and extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate 50:50 to 0:100 then ethyl acetate/methanol 100/0 to 70/30) to give the title compound (0.14 g, 55%) as a white solid. | CC(C)(C)c1ccccc1N1CCN(C(=O)C(=O)NC2CCS(=O)CC2)CC1 | null | 54.8 | null |
1,218,513 | ord_dataset-dc3bb1b1ac4e4229a3fc28fb559a9777 | null | 2012-01-01T00:10:00 | true | [S:1]=[C:2]1[C@H:8]([NH:9][C:10](=[O:19])[O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:7][CH2:6][C:5]2[CH:20]=[CH:21][CH:22]=[CH:23][C:4]=2[NH:3]1.[H-].[Na+].[CH3:26]I>C1COCC1>[CH3:26][S:1][C:2]1[C@H:8]([NH:9][C:10](=[O:19])[O:11][CH2:12][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH2:7][CH2:6][C:5]2[CH:20]=[CH:21][CH:22]=[CH:23][C:4]=2[N:3]=1 | O=C(N[C@@H]1CCc2ccccc2NC1=S)OCc1ccccc1 | CI | null | [H-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | 0 | null | Dissolve benzyl N-[(3R)-2-thioxo-1,3,4,5-tetrahydro-1-benzazepin-3-yl]carbamate (1.5 g, 4.60 mmol) in THF (40 mL), cool to 0° C., and add sodium hydride (NaH) (192.9 mg, 4.83 mmol, 60% in mineral oil) all at once. Remove the bath and stir the reaction for approximately 1 hour under nitrogen. Add methyl iodide (300 μL, 4.83 mmol) and stir for approximately 1 hour at ambient temperature. Concentrate the reaction under reduced pressure to remove most of the THF, dilute the residue with ethyl acetate, and wash with saturated sodium bicarbonate and brine, dry over sodium sulfate, and concentrate the organic layers under reduced pressure to give the title compound (1.5 g, 96%) as a white solid: MS (m/z): 341 (M+1). | CSC1=Nc2ccccc2CC[C@H]1NC(=O)OCc1ccccc1 | null | 95.8 | null |
1,089,950 | ord_dataset-52a37d876ddb453e86de0c15fa233d29 | null | 2011-01-01T00:09:00 | true | O1CCCC1.Br[C:7]1[CH:8]=[N:9][CH:10]=[C:11]([Br:13])[CH:12]=1.C([Mg]Cl)(C)C.[CH2:19]([O:21][C:22]1[CH:29]=[CH:28][C:25]([CH:26]=[O:27])=[CH:24][CH:23]=1)[CH3:20]>O>[Br:13][C:11]1[CH:12]=[C:7]([CH:26]([C:25]2[CH:28]=[CH:29][C:22]([O:21][CH2:19][CH3:20])=[CH:23][CH:24]=2)[OH:27])[CH:8]=[N:9][CH:10]=1 | CCOc1ccc(C=O)cc1 | Brc1cncc(Br)c1 | null | CC(C)[Mg]Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | C1CCOC1 | null | null | null | null | null | null | null | null | null | 25 | 2.5 | A tetrahydrofuran solution (25 mL) of 3,5-dibromo pyridine (5 g, 0.0211 mol) was added dropwise to a mixture of a tetrahydrofuran solution (21.1 mL) of 1M isopropyl magnesium chloride and tetrahydrofuran (10 mL) at 4° C. for 15 minutes. After stirred at room temperature for 2.5 hours, the reaction mixture was added with 4-ethoxybenzaldehyde (2.93 mL, 0.0211 mol) and stirred for further 1.5 hours. After the reaction mixture was added with water while cooled on ice and extracted with ethyl acetate, the organic phase was washed with brine and dried with anhydrous magnesium sulfate. After the desiccant was filtered off, the residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (hexane:ethyl acetate=1:1) to obtain (5-bromopyridine-3-yl)(4-ethoxyphenyl)methanol (5.0 g, 77%) as a yellow oily substance. | CCOc1ccc(C(O)c2cncc(Br)c2)cc1 | null | 76.9 | null |
470,038 | ord_dataset-f1b9e9741a6a4cc68e7070df811f86bb | null | 2000-01-01T00:07:00 | true | [F:1][C:2]([F:13])([F:12])[O:3][C:4]1[CH:11]=[CH:10][CH:9]=[CH:8][C:5]=1[CH2:6]Br.[C-:14]#[N:15].[Na+]>CN(C=O)C>[F:1][C:2]([F:13])([F:12])[O:3][C:4]1[CH:11]=[CH:10][CH:9]=[CH:8][C:5]=1[CH2:6][C:14]#[N:15] | FC(F)(F)Oc1ccccc1CBr | [C-]#N | null | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | 25 | 14 | To a stirred solution of 2-trifluoromethoxybenzyl bromide (0.95 g, 3.9 mmol) from Step 2 above in DMF (5 mL) was added NaCN (0.21 g, 4.3 mmol). The mixture was stirred at ambient temperature for 14 h and the solvent was removed under reduced pressure. The residue was purified by pressurized silica gel column chromatography using 15% EtOAc-hexanes as eluant to give 2-trifluoromethoxyphenylacetonitrile as a colorless liquid (TLC Rf =0.6 (solvent)). | N#CCc1ccccc1OC(F)(F)F | null | null | null |
61,113 | ord_dataset-912d62c1690b4ebfbe998c0c9baf88a8 | null | 1979-01-01T00:12:00 | true | [C:1]1(=[O:10])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.[CH3:11][N:12]([CH3:25])[CH2:13][CH2:14][CH2:15][O:16][C:17]1[CH:24]=[CH:23][C:20]([CH:21]=O)=[CH:19][CH:18]=1>>[CH3:25][N:12]([CH3:11])[CH2:13][CH2:14][CH2:15][O:16][C:17]1[CH:18]=[CH:19][C:20]([CH:21]=[C:2]2[CH2:3][C:4]3[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=3)[C:1]2=[O:10])=[CH:23][CH:24]=1 | O=C1CCc2ccccc21 | CN(C)CCCOc1ccc(C=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 | null | null | null | Interaction of 56 g of 1-indanone and 88 g of 4-(3-dimethylaminopropoxy)benzaldehyde according to the procedure described in Example 1A, gives 134.2 g of an oily product. | CN(C)CCCOc1ccc(C=C2Cc3ccccc3C2=O)cc1 | null | 98.5 | null |
646,990 | ord_dataset-5d77a731aa10488794c824ad12021f57 | null | 2004-01-01T00:09:00 | true | O1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[CH:11]=[CH:10][C:9]([N:12]2[CH2:17][CH2:16][N:15]([S:18]([CH2:21][CH:22]([CH:27]([CH3:29])[CH3:28])[C:23]([NH:25][OH:26])=[O:24])(=[O:20])=[O:19])[CH2:14][CH2:13]2)=[CH:8][CH:7]=1.CC(C)C(CS([N:40]1CCN(C2C=CC(C3C=NC=CC=3)=CC=2)C[CH2:41]1)(=O)=O)C(O)=O>>[N:40]1[CH:5]=[CH:4][CH:3]=[C:2]([C:6]2[CH:11]=[CH:10][C:9]([N:12]3[CH2:17][CH2:16][N:15]([S:18]([CH2:21][CH:22]([CH:27]([CH3:29])[CH3:28])[C:23]([NH:25][OH:26])=[O:24])(=[O:20])=[O:19])[CH2:14][CH2:13]3)=[CH:8][CH:7]=2)[CH:41]=1 | CC(C)C(CS(=O)(=O)N1CCN(c2ccc(-c3cccnc3)cc2)CC1)C(=O)O | CC(C)C(CS(=O)(=O)N1CCN(c2ccc(-c3ccco3)cc2)CC1)C(=O)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 | Prepared according to the method for the preparation of 2-[4-(4-furan-2-yl-phenyl)piperazine-1-sulfonylmethyl]-N-hydroxy-3-methylbutyramide, from 3-methyl-2-[4-(4-pyridin-3-yl-phenyl)piperazine-1-sulfonylmethyl]butyric acid (0.075 g), to yield the title compound as a white solid (0.059 g, 76%). | CC(C)C(CS(=O)(=O)N1CCN(c2ccc(-c3cccnc3)cc2)CC1)C(=O)NO | null | 76 | null |
1,346,331 | ord_dataset-6034127657614f02860ed057b62b882e | null | 2013-01-01T00:10:00 | true | Cl[C:2]1[O:3][C:4]([C:7]2[N:8]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C:9]3[C:14]([CH:15]=2)=[CH:13][C:12]([F:16])=[CH:11][CH:10]=3)=[CH:5][N:6]=1.[NH2:24][C:25]1[CH:26]=[C:27]([OH:31])[CH:28]=[CH:29][CH:30]=1>CC(O)C>[F:16][C:12]1[CH:13]=[C:14]2[C:9](=[CH:10][CH:11]=1)[N:8]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C:7]([C:4]1[O:3][C:2]([NH:24][C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([OH:31])[CH:26]=3)=[N:6][CH:5]=1)=[CH:15]2 | Nc1cccc(O)c1 | CC(C)(C)OC(=O)n1c(-c2cnc(Cl)o2)cc2cc(F)ccc21 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(C)O | null | null | null | null | null | null | null | null | null | null | 80 | null | A mixture of tert-butyl 2-(2-chlorooxazol-5-yl)-5-fluoro-1H-indole-1-carboxylate 50 (0.308 g, 0.916 mmol) and commercially available 3-aminophenol 8 (0.10 g, 0.916 mmol) in 2-propanol (20 mL) was heated to 80° C. for 18 h with stirring. Upon cooling, solvent was evaporated and silica column purified (Biotage) (Acetone/hexane as an eluent) to provide tert-butyl 5-fluoro-2-(2-((3-hydroxyphenyl)amino)oxazol-5-yl)-1H-indole-1-carboxylate 51 (0.15 g, 40% yield) as solid. MS (ES) m/z 410 (M+H+). | CC(C)(C)OC(=O)n1c(-c2cnc(Nc3cccc(O)c3)o2)cc2cc(F)ccc21 | null | 40 | null |
246,006 | ord_dataset-5eb2900a93c842ee98f26c305e657b61 | null | 1992-01-01T00:04:00 | true | [CH2:1]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[C:2]([CH3:5])([CH3:4])[CH3:3].[C:12]1(=[O:22])[O:17][C:15](=[O:16])[C:14]2=[CH:18][CH:19]=[CH:20][CH:21]=[C:13]12>>[CH2:1]([C:6]1[CH:7]=[CH:8][C:9]([C:12]([C:13]2[CH:21]=[CH:20][CH:19]=[CH:18][C:14]=2[C:15]([OH:17])=[O:16])=[O:22])=[CH:10][CH:11]=1)[C:2]([CH3:5])([CH3:4])[CH3:3] | CC(C)(C)Cc1ccccc1 | O=C1OC(=O)c2ccccc21 | null | null | null | null | null | null | null | 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 novel process, neopentylbenzene (1) is acylated in a first step with phthalic anhydride (2) under Friedel-Crafts conditions to give 2-(4-neopentylbenzoyl)-benzoic acid (3). ##STR3## | CC(C)(C)Cc1ccc(C(=O)c2ccccc2C(=O)O)cc1 | null | null | null |
663,154 | ord_dataset-5a3d853c53674888a5691dce2e398792 | null | 2005-01-01T00:03:00 | true | [F:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([NH:12][C@H:13]([C:15]([OH:17])=O)[CH3:14])=[O:11])[CH:5]=[C:6]([F:8])[CH:7]=1.Cl.[NH2:19][C@@H:20]([CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=1)[C:21]([O:23][CH3:24])=[O:22]>CO.C(Cl)Cl>[F:8][C:6]1[CH:5]=[C:4]([CH2:9][C:10]([NH:12][C@H:13]([C:15]([NH:19][C@@H:20]([CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=2)[C:21]([O:23][CH3:24])=[O:22])=[O:17])[CH3:14])=[O:11])[CH:3]=[C:2]([F:1])[CH:7]=1 | C[C@H](NC(=O)Cc1cc(F)cc(F)c1)C(=O)O | COC(=O)[C@@H](N)Cc1ccccn1 | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | CO | null | null | null | null | null | null | null | null | null | null | null | Following General Procedure A and using N-(3,5-difluorophenylacetyl)-L-alanine (from Example B2) and methyl (S)-2-amino-3-(2-pyridyl)propionate hydrochloride (Synthetech), the tide compound was prepared as a solid (mp=121-124° C.). The reaction was monitored by tlc (Rf=0.39 in 10% MeOH/DCM) and the product was purified by silica gel column chromatography. | COC(=O)[C@H](Cc1ccccn1)NC(=O)[C@H](C)NC(=O)Cc1cc(F)cc(F)c1 | null | null | null |
1,373,528 | ord_dataset-d23f2f15886d4c22b7d7ba5f0e203e81 | null | 2013-01-01T00:12:00 | true | [CH3:1][O:2][CH2:3][C:4]1([C:17](OCC)=[O:18])[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1.[H-].C([Al+]CC(C)C)C(C)C.O>C1(C)C=CC=CC=1>[OH:18][CH2:17][C:4]1([CH2:3][O:2][CH3:1])[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:15])([CH3:16])[CH3:14])=[O:11])[CH2:6][CH2:5]1 | CCOC(=O)C1(COC)CCN(C(=O)OC(C)(C)C)CC1 | null | null | CC(C)C[Al+]CC(C)C | [H-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | Cc1ccccc1 | null | null | null | null | null | null | null | null | null | 25 | 2 | To a solution of 1-tert-butyl 4-ethyl 4-(methoxymethyl)piperidine-1,4-dicarboxylate (2.05 g) in toluene (21 ml) was added 0.99 M solution of diisobutyl aluminum hydride in toluene (16.5 ml) under at 0° C. It was stirred at room temperature for 2 hours. Water was added and extracted with EtOAc. The organic phase was washed with water and brine, dried over MgSO4, evaporated off. The residue was purified by silica gel column to give tert-butyl 4-(hydroxymethyl)-4-(methoxymethyl)piperidine-1-carboxylate (0.95 g) as oil. | COCC1(CO)CCN(C(=O)OC(C)(C)C)CC1 | null | 53.9 | null |
1,721,080 | ord_dataset-36057d699ac5449e9c37eb99abf78b03 | null | 2016-01-01T00:05:00 | true | Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13].[NH2:15][CH2:16][CH2:17][CH:18]([O:22][CH2:23][CH3:24])[O:19][CH2:20][CH3:21].C(N(CC)CC)C>ClCCl>[CH2:20]([O:19][CH:18]([O:22][CH2:23][CH3:24])[CH2:17][CH2:16][NH:15][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13])[CH3:21] | CCOC(CCN)OCC | O=[N+]([O-])c1cnc2ccccc2c1Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(CC)CC | ClCCl | null | null | null | null | null | null | null | null | null | null | null | The general method described in Step 1 of Example 1 was used to react 4-chloro-3-nitroquinoline (20.3 g, 97.1 mmol), 1-amino-3,3-diethoxypropane (25.0 g, 116 mmol) and triethylamine (33.8 g, 333 mmol) in dichloromethane for 15 hours to provide (3,3-diethoxypropyl)-(3-nitroquinolin-4-yl)amine (30.5 g) as a yellow solid. | CCOC(CCNc1c([N+](=O)[O-])cnc2ccccc12)OCC | null | 98.4 | null |
1,684,847 | ord_dataset-3953983e052a4076aa7cc0880b79cb8b | null | 2016-01-01T00:01:00 | true | [NH2:1][CH:2]([C:11]1[C:16]([O:17][CH3:18])=[CH:15][CH:14]=[CH:13][C:12]=1[O:19][CH3:20])[CH2:3][CH:4]([CH3:10])[C:5]([O:7]CC)=O.[F:21][CH:22]([F:34])[O:23][C:24]1[CH:31]=[CH:30][C:27]([CH:28]=O)=[CH:26][C:25]=1[O:32][CH3:33]>>[F:21][CH:22]([F:34])[O:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28][N:1]2[CH:2]([C:11]3[C:12]([O:19][CH3:20])=[CH:13][CH:14]=[CH:15][C:16]=3[O:17][CH3:18])[CH2:3][CH:4]([CH3:10])[C:5]2=[O:7])=[CH:26][C:25]=1[O:32][CH3:33] | COc1cc(C=O)ccc1OC(F)F | CCOC(=O)C(C)CC(N)c1c(OC)cccc1OC | null | null | null | null | null | null | null | 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 described general procedure 2 (GP2) by reaction of ethyl 4-amino-4-(2,6-dimethoxyphenyl)-2-methylbutanoate with commercially available 4-(difluoromethoxy)-3-methoxybenzaldehyde. Subsequent purification by preparative HPLC afforded the target compound. LC-MS (conditions A): tR=0.85 min.; [M+H]+: 422.01 g/mol. | COc1cc(CN2C(=O)C(C)CC2c2c(OC)cccc2OC)ccc1OC(F)F | null | null | null |
1,453,741 | ord_dataset-a86112d52cd54525a5e36d41f18aced2 | null | 2014-01-01T00:07:00 | true | [OH-].[Li+].[Br:3][C:4]1[CH:5]=[CH:6][C:7]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([C:30]#[N:31])[CH:25]=2)=[C:8]([CH:21]=1)[C:9]([O:11]CC1C=CC=C(C#N)C=1)=[O:10]>O.C1COCC1>[Br:3][C:4]1[CH:5]=[CH:6][C:7]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([C:30]#[N:31])[CH:25]=2)=[C:8]([CH:21]=1)[C:9]([OH:11])=[O:10] | N#Cc1cccc(COC(=O)c2cc(Br)ccc2OCc2cccc(C#N)c2)c1 | null | null | [Li+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | O | null | null | null | null | null | null | null | null | null | 20 | 16 | A solution of lithium hydroxide (386 mg, 9.19 mmol) in water (20.00 mL) was added dropwise to a stirred solution of (3-cyanophenyl)methyl 5-bromo-2-{[(3-cyanophenyl)methyl]oxy}benzoate (may be prepared as described in Description 25; 411 mg, 0.92 mmol) in THF (20 ml) over 1 min. The reaction mixture was stirred at 20° C. for 16 h. The organic phase was evaporated and the aqueous phase (20 ml) was extracted by ethyl acetate (20 ml). The aqueous phase (20 ml) was adjusted to pH 2 with 2M hydrochloric acid (1 ml). The aqueous phase was then extracted with ethyl acetate (3×20 ml). The organic phase was evaporated in vacuo to yield the title compound as an off-white solid. 200 mg. | N#Cc1cccc(COc2ccc(Br)cc2C(=O)O)c1 | null | null | null |
138,762 | ord_dataset-3fa0a6b7d51b4fc6a5380aa0d03ac884 | null | 1985-01-01T00:12:00 | true | [CH3:1][CH:2]1[CH2:7][NH:6][CH2:5][CH:4]([CH3:8])[NH:3]1.[CH3:9][CH:10]([CH3:14])[C:11](Cl)=[O:12]>>[CH3:9][CH:10]([CH3:14])[C:11]([N:3]1[CH:4]([CH3:8])[CH2:5][N:6]([C:11](=[O:12])[CH:10]([CH3:14])[CH3:9])[CH2:7][CH:2]1[CH3:1])=[O:12] | CC(C)C(=O)Cl | CC1CNCC(C)N1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The reaction of 5.7 g (0.05 mole) of 2,6-dimethylpiperazine with 13.85 g (0.13 mole) of 2-methylpropionyl chloride is carried out as described in Example VI, and yields 13.3 g of crude product as a solid. Recrystallization from acetone provides 7.1 g of the pure product: mp, 160°-161° C. An additional 4.0 g of pure product is obtained by concentrating the mother liquor and adding hexane. The assigned product structure is consistent with IR and NMR data. | CC(C)C(=O)N1CC(C)N(C(=O)C(C)C)C(C)C1 | null | 55.8 | null |
601,928 | ord_dataset-82e842e611ef4a05b6e7f9ea0a46d52d | null | 2003-01-01T00:07:00 | true | [C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][C:15]2[C:20]([O:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[O:28][CH3:29])=[C:19]([O:30][CH2:31][CH2:32][CH2:33][NH2:34])[N:18]=[C:17]([C:35]3[N:40]=[CH:39][CH:38]=[CH:37][N:36]=3)[N:16]=2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[S:41]1[CH:45]=[CH:44][CH:43]=[C:42]1[S:46](Cl)(=[O:48])=[O:47]>>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][C:15]2[C:20]([O:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[O:28][CH3:29])=[C:19]([O:30][CH2:31][CH2:32][CH2:33][NH:34][S:46]([C:42]3[S:41][CH:45]=[CH:44][CH:43]=3)(=[O:48])=[O:47])[N:18]=[C:17]([C:35]3[N:36]=[CH:37][CH:38]=[CH:39][N:40]=3)[N:16]=2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:2])[CH3:3] | O=S(=O)(Cl)c1cccs1 | COc1ccccc1Oc1c(NS(=O)(=O)c2ccc(C(C)(C)C)cc2)nc(-c2ncccn2)nc1OCCCN | null | null | null | null | null | null | null | 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 procedure described in Example 4a) 100 mg 4-tert.-butyl-N-[6-(3-aminopropoxy)-5-(o-methoxyphenoxy)-2-pyrimidinyl-4-pyrimidinyl]-benzene-sulfonamide was reacted with 2-thiophenesulfonylchloride to give 50 mg 4-tert.-butyl-N-[6-(3-(2-thiophenesulfonylamino)-propoxy)-5-(o-methoxyphenoxy)-2-pyrimidinyl-4-pyrimidinyl]-benzene-sulfonamide. LC-MS: tR=5.63 min, [M+1]+711.28, [M−1]−=709.36. | COc1ccccc1Oc1c(NS(=O)(=O)c2ccc(C(C)(C)C)cc2)nc(-c2ncccn2)nc1OCCCNS(=O)(=O)c1cccs1 | null | null | null |
323,704 | ord_dataset-24ad29d930104afea313b6c3bd11099e | null | 1996-01-01T00:01:00 | true | [C:1](Cl)(=[O:5])[CH2:2][CH2:3][CH3:4].[C:7]1([N:13]2[C:17]([NH2:18])=[C:16]([C:19]#[N:20])[CH:15]=[N:14]2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.Cl>N1C=CC=CC=1>[C:7]1([N:13]2[C:17]([NH:18][C:1]([CH2:2][CH2:3][CH3:4])=[O:5])=[C:16]([C:19]#[N:20])[CH:15]=[N:14]2)[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1 | N#Cc1cnn(-c2ccccc2)c1N | CCCC(=O)Cl | null | Cl | 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 | 50 | null | 6.8 ml (66 mmol) of butyryl chloride were added to a solution of 5.52 g (30 mmol) of 1-phenyl-4-cyano-5-aminopyrazole [known from J. Org. Chem. 21 (1956), 1240] in 70 ml of pyridine. The mixture was heated for 15 hours at 50° C. and then poured into 500 ml of 5% strength by weight aqueous hydrochloric acid. The product was extracted from the aqueous phase with methylene chloride and then isolated in a conventional manner. Yield: 50%. | CCCC(=O)Nc1c(C#N)cnn1-c1ccccc1 | null | 50 | null |
697,156 | ord_dataset-4e9c2fa02a7544fd839206719263345f | null | 2006-01-01T00:02:00 | true | ClN1C(=O)CCC1=O.[F:9][C:10]([F:19])([F:18])[C:11]1[CH:17]=[CH:16][C:14]([NH2:15])=[CH:13][CH:12]=1.[CH3:20][S:21][CH3:22]>ClCCl>[CH3:20][S:21]([CH3:22])=[N:15][C:14]1[CH:16]=[CH:17][C:11]([C:10]([F:18])([F:19])[F:9])=[CH:12][CH:13]=1 | CSC | Nc1ccc(C(F)(F)F)cc1 | null | O=C1CCC(=O)N1Cl | 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 | 2.5 | 1 | A solution of N-chlorosuccinimide (12-43 g, 93.1 mmol) in ˜170 mL of dichloromethane was added to a mixture of 4-(trifluoromethyl) aniline (15 g, 93.1 mmol) and dimethyl sulfide (6.35 g, 102 mmol) in 230 mL of dichloromethane at −5-0° C. After the addition was complete, the mixture was stirred at 0-5° C. for 1 h, and N-chlorosuccinimide (0.02 g, 4.64 mmol) was added. After a further 30 minutes, the mixture was washed with 500 mL of 1N sodium hydroxide. | CS(C)=Nc1ccc(C(F)(F)F)cc1 | null | null | null |
522,944 | ord_dataset-262b40ea420c471da9b9244fe9b8f645 | null | 2001-01-01T00:10:00 | true | [OH:1][C@@H:2]([C@H:4]1[C:33](=[O:34])[N:6]2[C:7]([C:20]([O:22]CC3C=CC([N+]([O-])=O)=CC=3)=[O:21])=[C:8]([C:11]3[N+:12]4[C:13](=[CH:16][N:17]([CH3:19])[CH:18]=4)[S:14][CH:15]=3)[C@H:9]([CH3:10])[C@H:5]12)[CH3:3].P([O-])([O-])([O-])=O>C1COCC1.[Pd]>[OH:1][C@@H:2]([C@H:4]1[C:33](=[O:34])[N:6]2[C:7]([C:20]([O-:22])=[O:21])=[C:8]([C:11]3[N+:12]4[C:13](=[CH:16][N:17]([CH3:19])[CH:18]=4)[S:14][CH:15]=3)[C@H:9]([CH3:10])[C@H:5]12)[CH3:3] | C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(c3csc4cn(C)c[n+]34)[C@H](C)[C@H]12 | null | null | [Pd] | O=P([O-])([O-])[O-] | 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 | 3.5 | To a solution of 60.5 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(6-methylimidazo[5,1-b]thiazolium-3-yl)-1-carbapen-2-em-3-carboxylate in 1.8 ml of THF and 1.8 ml of {fraction (1/15)} M phosphate buffer (pH 6.8) was added 71 mg of 10% Pd-C. The reactor was purged with hydrogen, and the reaction mixture was stirred at room temperature for 3.5 hours. The catalyst was collected by filtration through Celite, and washed with water. The filtrate was washed with 20 ml of ethyl acetate, and purified by column chromatography on DIAION HP-20 and on COSMOSEAL40C18-PREP (water:methanol=20:1) to give 8.3 mg of the title compound. | C[C@@H](O)[C@H]1C(=O)N2C(C(=O)[O-])=C(c3csc4cn(C)c[n+]34)[C@H](C)[C@H]12 | null | 19.1 | null |
965,440 | ord_dataset-03ba810b7f464a06b5d8787af2e8b64e | null | 2010-01-01T00:06:00 | true | [CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]([O:13][C:14]2[CH:15]=[C:16]3[C:20](=[CH:21][CH:22]=2)[N:19]([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[N:18]=[CH:17]3)[C@@H:10]([NH2:12])[CH3:11])=[CH:5][CH:4]=1)[CH3:2].C([O:33][CH2:34][C:35](Cl)=[O:36])(=O)C>>[CH2:1]([C:3]1[CH:4]=[CH:5][C:6]([C@@H:9]([O:13][C:14]2[CH:15]=[C:16]3[C:20](=[CH:21][CH:22]=2)[N:19]([C:23]2[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=2)[N:18]=[CH:17]3)[C@@H:10]([NH:12][C:34](=[O:33])[CH2:35][OH:36])[CH3:11])=[CH:7][CH:8]=1)[CH3:2] | CC(=O)OCC(=O)Cl | CCc1ccc([C@@H](Oc2ccc3c(cnn3-c3ccc(F)cc3)c2)[C@H](C)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 | Prepared as described in Example 5 using (1R,2S)-1-(4-ethylphenyl)-1-{[1-(4-fluorophenyl)-1H-indazol-5-yl]oxy}propan-2-amine (20 mg, 50 μmol) and 2-chloro-2-oxoethyl acetate (21 mg, 150 μmol). Yield 21 mg (91%). | CCc1ccc([C@@H](Oc2ccc3c(cnn3-c3ccc(F)cc3)c2)[C@H](C)NC(=O)CO)cc1 | null | null | null |
1,429,358 | ord_dataset-5e6956e6e8c24a168866a253f4a66c6c | null | 2014-01-01T00:05:00 | true | C[O:2][C:3](=[O:22])[CH2:4][NH:5][C:6]([C:8]1[C:13]([OH:14])=[CH:12][C:11]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[CH:16]=2)=[CH:10][N:9]=1)=[O:7].[OH-].[Na+].Cl>C1COCC1>[Cl:21][C:17]1[CH:16]=[C:15]([C:11]2[CH:12]=[C:13]([OH:14])[C:8]([C:6]([NH:5][CH2:4][C:3]([OH:22])=[O:2])=[O:7])=[N:9][CH:10]=2)[CH:20]=[CH:19][CH:18]=1 | COC(=O)CNC(=O)c1ncc(-c2cccc(Cl)c2)cc1O | null | null | Cl | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | 25 | 1 | To a solution of {[5-(3-chloro-phenyl)-3-hydroxy-pyridine-2-carbonyl]-amino}-acetic acid methyl ester, 6, (0.163 g, 0.509 mmol) in THF (5 mL) is added 1M NaOH (1.5 ml, 1.27 mmol) and the reaction mixture stirred at room temperature for 1 hour. The solution is acidified using 1M HCl (3 mL), the solvent removed under reduced pressure and the resulting solid suspended in CHCl3:iso-propanol (1:1), filtered and the filtrate dried (MgSO4), filtered and re-concentrated under reduced pressure. The crude material is triturated with a small amount of MeOH to afford 0.10 g (64% yield) of the desired product as a colorless solid. 1H NMR (400 MHz, MeOD) δ ppm 8.31 (1H, d, J=1.8 Hz), 7.47 (2H, d, J=1.8 Hz), 7.30-7.65 (4H, m), 4.07 (2H, s). HPLC-MS: m/z 307 [M+H]+. | O=C(O)CNC(=O)c1ncc(-c2cccc(Cl)c2)cc1O | null | 64 | null |
1,504,660 | ord_dataset-1a1aa5d1c3224edca0aec6e3398da985 | null | 2014-01-01T00:11:00 | true | [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:14]([NH:16][CH3:17])=O)[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.Cl>>[ClH:1].[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([CH2:14][NH:16][CH3:17])[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)=[CH:6][CH:7]=1 | CNC(=O)C1(c2ccc(Cl)cc2)CCCCC1 | 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 | null | The title compound was synthesized from 1-(4-chlorophenyl)-N-methylcyclohexanecarboxamide (278 mg, 1.11 mmol) using General Procedure E, followed by HCl salt formation to give pure (1-(4-chlorophenyl)cyclohexyl)-N-methylmethanamine hydrochloride as an off-white solid (185 mg, 70%). HPLC Rt=8.38 min; 1H NMR (400 mHz, MeOH-d4) 7.39 (s, 4H), 3.10 (s, 2H), 2.52 (s, 3H), 2.19-2.16 (m, 2H), 1.65-1.49 (m, 6H), 1.37-1.30 (m, 4H); LC-MS 7.49 min, (M+1)+0 238 @ 7.63 min. | CNCC1(c2ccc(Cl)cc2)CCCCC1 | null | 121.6 | null |
1,096,896 | ord_dataset-af85e6f81c2d49f08086afd6d9e6959c | null | 2011-01-01T00:10:00 | true | [CH2:1]([O:3][P:4]([C:9]([C:11]([P:13]([O:18][CH2:19][CH3:20])([O:15][CH2:16][CH3:17])=[O:14])=[CH2:12])=[CH2:10])([O:6][CH2:7][CH3:8])=[O:5])[CH3:2].O.O.O.O.O.O.O.O.O.[S-2:30].[Na+].[Na+]>C(O)C>[CH2:16]([O:15][P:13]([CH:11]1[CH:9]([P:4]([O:6][CH2:7][CH3:8])([O:3][CH2:1][CH3:2])=[O:5])[CH2:10][S:30][CH2:12]1)([O:18][CH2:19][CH3:20])=[O:14])[CH3:17] | [S-2] | C=C(C(=C)P(=O)(OCC)OCC)P(=O)(OCC)OCC | null | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CCO | null | null | null | null | null | null | null | null | null | 25 | 72 | In ethanol, 2.02 g (6.19 mmols) of 2,3-bis(diethoxyphosphoryl)-1,3-butadiene was dissolved, to which 1.63 g (6.81 mmols) of commercially available sodium sulfide nonahydrate was added, followed by stirring at room temperature for 3 days. After completion of the reaction, the reaction mixture was dried over anhydrous sodium sulfate for 1 hour. Ethyl acetate was added to and the resulting mixture was charged into a silica gel column to dissolve out the specified substance with ethyl acetate. Thereafter, the solvent was removed, and the resulting crude product was purified with a silica gel column (ethyl acetate:chloroform=1:2) to obtain the specified substance in the form of a yellow oil at a yield of 1.88 g (yield: 84.3%). | CCOP(=O)(OCC)C1CSCC1P(=O)(OCC)OCC | null | 84.3 | null |
609,342 | ord_dataset-73916d628db147c89020b3baac642d48 | null | 2003-01-01T00:09:00 | true | [O-]CC.[Na+].C(O)C.[CH2:8]([CH:15](C(C)=O)[C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[Br:24]N1C(=O)CCC1=O>>[Br:24][C:14]1[C:9]([CH2:8][CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:10][CH:11]=[CH:12][CH:13]=1 | CCOC(=O)C(Cc1ccccc1)C(C)=O | O=C1CCC(=O)N1Br | null | CC[O-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | null | null | null | null | null | null | null | null | null | null | 22.5 | 0.5 | To a 2 L 4-necked round bottom flask that was equipped with an overhead stirrer, an addition funnel, a condenser and a temperature-probe, was added the solution of sodium ethoxide/ethanol (21% wt. %, 161.8 g) at 20-25° C. under nitrogen. Ethyl 2-benzylacetoacetate (103.1 g, 0.454 mole) was added dropwise. The resulting solution was stirred at 20-25° C. for 30 minutes. The reaction mixture was then cooled to −35° C. with a dry ice/acetone bath. N-Bromosuccinimide (NBS; 97.95 g, 0.545 mole) was added portion-wise over 30 minutes. After the addition was over, the reaction mixture was stirred at −35° C. for 1 hr before warming up to 20-25° C. and it was stirred for an additional 2 hrs. The reaction was then quenched with water (400 mL) and ethyl acetate (600 mL) was added. The layers were separated and the product was extracted from aqueous layer with ethyl acetate (400 mL×3). The combined organic layers was washed with saturated sodium bicarbonate twice (400 mL×2), water twice (400 mL×2) and brine (500 mL). After the removal of solvent, the product (crude, 132 g) was distilled under reduced pressure. Ethyl 2-bromo-3-benzenepropanoate (97.7 g) was obtained at yield 83.7%. | CCOC(=O)CCc1ccccc1Br | null | 83.7 | null |
578,264 | ord_dataset-a9ba4801408c4b01922886164c10a391 | null | 2003-01-01T00:01:00 | true | [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([C@H:16]([C:41]([NH2:43])=[O:42])[CH2:17][CH2:18][CH2:19][CH2:20][NH:21][C:22]([C@@H:24]([NH:32][S:33]([C:36]2[S:40][CH:39]=[CH:38][CH:37]=2)(=[O:35])=[O:34])[CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:23])[CH2:12][CH:13]([CH3:15])[CH3:14])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[CH2:44]([CH2:46]N)[OH:45]>C(O)C>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([N:11]([C@H:16]([C:41]([NH:43][CH2:46][CH2:44][OH:45])=[O:42])[CH2:17][CH2:18][CH2:19][CH2:20][NH:21][C:22]([C@@H:24]([NH:32][S:33]([C:36]2[S:40][CH:39]=[CH:38][CH:37]=2)(=[O:34])=[O:35])[CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:23])[CH2:12][CH:13]([CH3:15])[CH3:14])(=[O:9])=[O:10])=[CH:6][CH:7]=1 | Cc1ccc(S(=O)(=O)N(CC(C)C)[C@@H](CCCCNC(=O)[C@H](Cc2ccccc2)NS(=O)(=O)c2cccs2)C(N)=O)cc1 | NCCO | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | null | null | null | null | null | null | null | null | null | null | null | 3 | A portion of the crude intermediate of example 58 above, (25 mg, 0.03 mmol) was added to a solution of ethanolamine in ethanol (1M, 10 mL). The resulting solution was stirred for 3 h before evaporation of the solvent. The residue was purified by preparative HPLC to yield 15 mg, 21% of the desired material. | Cc1ccc(S(=O)(=O)N(CC(C)C)[C@@H](CCCCNC(=O)[C@H](Cc2ccccc2)NS(=O)(=O)c2cccs2)C(=O)NCCO)cc1 | null | 21 | null |
1,271,500 | ord_dataset-d3580a12b15e46cc91aa73f4f1a4a8cc | null | 2013-01-01T00:03:00 | true | O.[OH-].[Li+].[Cl:4][C:5]1[CH:6]=[C:7]([N:12]2[C:16]([C:17]3[CH:22]=[C:21]([F:23])[CH:20]=[C:19]([C:24]#[N:25])[CH:18]=3)=[CH:15][C:14]([C:26]([O:28]CC)=[O:27])=[N:13]2)[CH:8]=[CH:9][C:10]=1[F:11].Cl>C1COCC1>[Cl:4][C:5]1[CH:6]=[C:7]([N:12]2[C:16]([C:17]3[CH:22]=[C:21]([F:23])[CH:20]=[C:19]([C:24]#[N:25])[CH:18]=3)=[CH:15][C:14]([C:26]([OH:28])=[O:27])=[N:13]2)[CH:8]=[CH:9][C:10]=1[F:11] | CCOC(=O)c1cc(-c2cc(F)cc(C#N)c2)n(-c2ccc(F)c(Cl)c2)n1 | null | null | Cl | [Li+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | O | null | null | null | null | null | null | null | null | null | 25 | 6 | 12.0 ml of water and 741 mg (30.1 mmol) of lithium hydroxide are added to 1.20 g (3.10 mmol) of the carboxylic ester of Example 128A in 36.0 ml of THF. The mixture is stirred at RT for 6 h and a 1N aqueous hydrogen chloride solution is subsequently added to the reaction solution. The mixture is extracted with dichloromethane and the combined organic phases are dried over magnesium sulfate, filtered and concentrated in vacuo. 1.10 g (95% of theory) of the title compound are obtained. | N#Cc1cc(F)cc(-c2cc(C(=O)O)nn2-c2ccc(F)c(Cl)c2)c1 | null | null | null |
1,245,658 | ord_dataset-c544c0c663f54dbea4ddb52ddde7934e | null | 2013-01-01T00:01:00 | true | [O:1]=[CH:2][C:3]1[CH:11]=[CH:10][C:7]([O:8][CH3:9])=[C:5]([OH:6])[CH:4]=1.[N+:12]([O-])([OH:14])=[O:13]>C(O)(=O)C>[N+:12]([C:10]1[C:7]([O:8][CH3:9])=[C:5]([OH:6])[CH:4]=[C:3]([CH:11]=1)[CH:2]=[O:1])([O-:14])=[O:13] | O=[N+]([O-])O | COc1ccc(C=O)cc1O | 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 | 27.5 | null | Isovanillin (500 gm) and acetic acid (1750 ml) were cooled to −5 to 0° C. To this solution, nitric acid (750 ml) was charged slowly at −5 to 0° C. with stirring. The temperature of the reaction mass was slowly raised to 25-30° C. and maintained for 12 hours. The reaction mass was quenched into ice water (4 kg), the solids filtered and washed with water (2 lt). The solids were stirred with a 1% sodium bicarbonate solution (1 lt), filtered and dried at 45-50° C. The solid was dissolved in 6 volumes of ethyl acetate, ethyl acetate was distilled off up to half the volume and 3 volumes of n-Hexane were charged slowly at 45-50° C. The reaction mass was cooled slowly to 0-5° C., maintained for 1 hour, the solids filtered, washed with 0.5 volumes of 1:1 mixture of ethyl acetate:n-Hexane and dried at 45-50° C. to yield the title compound (423 gm, 65% yield). | COc1c(O)cc(C=O)cc1[N+](=O)[O-] | null | 65 | null |
1,161,981 | ord_dataset-d24cc23b3db94284bb83a2ccdd9eb880 | null | 2012-01-01T00:05:00 | true | [N+:1]([C:4]1[CH:5]=[N:6][CH:7]=[CH:8][C:9]=1[C:10]1[CH2:15][CH2:14][CH2:13][C:12](=[O:16])[CH:11]=1)([O-:3])=[O:2].[BH4-].[Na+]>CCO>[N+:1]([C:4]1[CH:5]=[N:6][CH:7]=[CH:8][C:9]=1[C:10]1[CH2:15][CH2:14][CH2:13][CH:12]([OH:16])[CH:11]=1)([O-:3])=[O:2] | O=C1C=C(c2ccncc2[N+](=O)[O-])CCC1 | null | null | [BH4-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | null | null | null | null | null | null | null | null | null | null | 0 | 2 | To a solution of 3-(3-nitropyridin-4-yl)cyclohex-2-enone (1.0 equiv.) was added EtOH (1.1 M) and CeCl3-7H2O (1.3 equiv.). The reaction was cooled to 0° C., then NaBH4 (1.3 equiv.) was added in portions. Stirred for 2 h at 0° C., then quenched by adding water, concentrated to remove the EtOH, added EtOAc, extracted the organics, dried with brine, then Na2SO4, and concentrated to yield 3-(3-nitropyridin-4-yl)cyclohex-2-enol (99%). LC/MS=221.1 (M+H), LC=2.24 min. | O=[N+]([O-])c1cnccc1C1=CC(O)CCC1 | null | 99 | null |
81,945 | ord_dataset-b1023e5ccd7142de9d250aa2e3e124db | null | 1981-01-01T00:06:00 | true | [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9](=[S:21])[S:10][CH2:11][CH2:12][C:13](=[O:20])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[N:6][CH:7]=1.[BH4-].[K+]>CO.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9](=[S:21])[S:10][CH2:11][CH2:12][CH:13]([OH:20])[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)=[N:6][CH:7]=1 | O=C(CCSC(=S)Nc1ccc(Cl)cn1)c1ccccc1 | null | null | [BH4-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | O | null | null | null | null | null | null | null | null | null | null | 20 | The procedure of Example 3 is followed, but a suspension of 3-oxo-3-phenylpropyl 5-chloropyrid-2-yldithiocarbamate (28.0 g) in methanol (840 cc) and a solution of potassium borohydride (9.0 g) in distilled water (120 cc) are used as the starting materials at a maximum of 30° C. The reaction is allowed to proceed for 20 hours at between 20° and 25° C. Unreacted starting material (5.5 g) is filtered off from the reaction mixture. The filtrate is evaporated to dryness. The residue (20.0 g) is dissolved in chloroform (200 cc). The solution is chromatographed on silica (0.063-0.2 mm, 400 g) contained in a column of diameter 5 cm. Elution is carried out with chloroform (2 liters), this eluate being discarded, and then with chloroform (4.5 liters). The eluate which is collected is evaporated to dryness under reduced pressure (20 mm Hg) at 45° C. The chromatographed product (14.4 g) is recrystallised from acetonitrile (40 cc). 3-Hydroxy-3-phenylpropyl 5-chloropyrid-2-yldithiocarbamate (9.8 g), which melts at 91° C., is obtained. | OC(CCSC(=S)Nc1ccc(Cl)cn1)c1ccccc1 | null | 34.8 | null |
1,382,772 | ord_dataset-31641fb65b34430fa7435229b949b604 | null | 2014-01-01T00:01:00 | true | [CH3:1][C:2]1[C:3](Cl)=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.CCN(C(C)C)C(C)C.[CH:19]([NH:22][C:23]([C@H:25]1[CH2:29][CH2:28][CH2:27][C@H:26]1[NH2:30])=[O:24])([CH3:21])[CH3:20]>CC(N(C)C)=O>[CH:19]([NH:22][C:23]([C@H:25]1[CH2:29][CH2:28][CH2:27][C@H:26]1[NH:30][C:3]1[C:2]([CH3:1])=[CH:7][N:6]=[C:5]([Cl:8])[N:4]=1)=[O:24])([CH3:21])[CH3:20] | Cc1cnc(Cl)nc1Cl | CC(C)NC(=O)[C@H]1CCC[C@H]1N | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(C(C)C)C(C)C | CC(=O)N(C)C | null | null | null | null | null | null | null | null | null | 70 | 1 | 1 g (6.1 mmol, 1 eq) 5-methyl-2,4-dichloropyrimidine (prepared analogously to A-1a) are dissolved in 3 mL DMA and then 5.3 mL (30.5 mmol, 5 eq) Hünig base are added dropwise. 1.03 g (6.1 mmol, 1 eq) (1S,2R)-2-aminocyclopentanecarboxylic acid isopropylamide are added and the reaction mixture is stirred for 1 h at 70° C. HPLC monitoring shows that the reaction is total and only one regioisomer is formed. The reaction mixture is combined with RP gel, the volatile constituents are eliminated in vacuo, the product is purified by column chromatography through an RP phase and isolated (from water/MeCN (+0.2% HCOOH in each case) from 82/18 to 60/40 in 15 min). Corresponding product fractions are combined, freed from the solvent by freeze-drying and 956 mg of C-1d are obtained. | Cc1cnc(Cl)nc1N[C@@H]1CCC[C@@H]1C(=O)NC(C)C | null | null | null |
80,358 | ord_dataset-2d589ad46f82417ab9ddc07f7655411c | null | 1981-01-01T00:04:00 | true | [O:1]=[C:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[S:6](=[O:14])(=[O:13])[C:5]2[CH:15]=[C:16]([C:19]([O:21]C)=[O:20])[CH:17]=[CH:18][C:4]=2[NH:3]1>[OH-].[Na+].O1CCCC1>[O:1]=[C:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[S:6](=[O:14])(=[O:13])[C:5]2[CH:15]=[C:16]([C:19]([OH:21])=[O:20])[CH:17]=[CH:18][C:4]=2[NH:3]1 | COC(=O)c1ccc2c(c1)S(=O)(=O)c1ccccc1C(=O)N2 | null | null | [Na+] | [OH-] | 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 | Stir at room temperature 795 mg of the ester of Example 26 in a mixture of 50 ml of 10% aqueous sodium hydroxide and 50 ml of tetrahydrofuran for 3 hours. Separate the layers and extract the organic layer with 10% aqueous sodium hydroxide. Wash the combined aqueous layers with ether and acidify with acetic acid. Separate the precipitate by filtration, wash with water and dry in order to obtain the title product (m.p. 337°-340° C. with subsequent dec.). | O=C(O)c1ccc2c(c1)S(=O)(=O)c1ccccc1C(=O)N2 | null | null | null |
1,155,506 | ord_dataset-b195433d5c354ddfb6cde0d53c41910f | null | 2012-01-01T00:04:00 | true | [F:1][C:2]1[C:7]([C:8]2[CH:9]=[C:10]([C@:14]34[CH2:22][NH:21][CH2:20][C@H:19]3[CH2:18][S:17][C:16]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[N:15]4)[CH:11]=[CH:12][CH:13]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.[F:31][C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1.C(N(CC)CC)C>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[F:31][C:32]1[CH:37]=[CH:36][C:35]([N:21]2[CH2:20][C@@H:19]3[C@@:14]([C:10]4[CH:11]=[CH:12][CH:13]=[C:8]([C:7]5[C:2]([F:1])=[N:3][CH:4]=[CH:5][CH:6]=5)[CH:9]=4)([N:15]=[C:16]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:27])([CH3:29])[CH3:28])[S:17][CH2:18]3)[CH2:22]2)=[CH:34][CH:33]=1 | OB(O)c1ccc(F)cc1 | CC(C)(C)OC(=O)NC1=N[C@@]2(c3cccc(-c4cccnc4F)c3)CNC[C@H]2CS1 | null | [Cu+2] | CC(=O)[O-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | CCN(CC)CC | null | null | null | null | null | null | null | null | null | 25 | 0.5 | tert-Butyl(±)-{(4aR*,7aS*)-7a-[3-(2-fluoropyridin-3-yl)phenyl]-4,4a,5,6,7,7a-hexahydropyrrolo[3,4-d][1,3]thiazin-2-yl}carbamate obtained in Preparation Example 18-(9) (72 mg) was mixed with 4-fluorobenzeneboronic acid (24.7 mg), copper (II)acetate (6.1 mg), triethylamine (93.2 μL, specific gravity: 0.73 g/cm3) and molecular sieves 4 A (powder) (57.6 mg) in dichloromethane (3 mL), and the mixture was stirred under a nitrogen atmosphere at room temperature for 11 hours and 30 minutes. 4-Fluorobenzeneboronic acid (23.5 mg) and copper (II) acetate (12 mg) were further added. The atmosphere was changed to an open system, followed by further stirring. After 23 hours and 45 minutes, the reaction suspension was purified by NH-silica gel column chromatography. The resulting product was purified again by pTLC to obtain the title compound (15 mg). | CC(C)(C)OC(=O)NC1=N[C@@]2(c3cccc(-c4cccnc4F)c3)CN(c3ccc(F)cc3)C[C@H]2CS1 | null | null | null |
349,769 | ord_dataset-66f304805e5d47fc8d3c722b1bd8dfa2 | null | 1996-01-01T00:12:00 | true | [CH2:1]([C:5]1[N:9]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3[C:18]([C:23]([O:25]C(C)(C)C)=[O:24])=[CH:19][CH:20]=[CH:21][CH:22]=3)=[CH:13][CH:12]=2)[C:8]2[CH:30]=[C:31]([N:34]([CH3:45])[S:35]([CH2:38][C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)(=[O:37])=[O:36])[CH:32]=[CH:33][C:7]=2[N:6]=1)[CH2:2][CH2:3][CH3:4].FC(F)(F)C(O)=O>C(Cl)Cl>[CH2:1]([C:5]1[N:9]([CH2:10][C:11]2[CH:12]=[CH:13][C:14]([C:17]3[C:18]([C:23]([OH:25])=[O:24])=[CH:19][CH:20]=[CH:21][CH:22]=3)=[CH:15][CH:16]=2)[C:8]2[CH:30]=[C:31]([N:34]([CH3:45])[S:35]([CH2:38][C:39]3[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=3)(=[O:36])=[O:37])[CH:32]=[CH:33][C:7]=2[N:6]=1)[CH2:2][CH2:3][CH3:4] | CCCCc1nc2ccc(N(C)S(=O)(=O)Cc3ccccc3)cc2n1Cc1ccc(-c2ccccc2C(=O)OC(C)(C)C)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O=C(O)C(F)(F)F | ClCCl | null | null | null | null | null | null | null | null | null | null | null | Prepared analogously to Example 1 from tert.-butyl 4'-[[2-n-butyl-6-(N-phenylmethanesulphonyl-methylamino)-benzimidazol-1-yl]methyl]biphenyl-2-carboxylate and trifluoroacetic acid in methylene chloride. | CCCCc1nc2ccc(N(C)S(=O)(=O)Cc3ccccc3)cc2n1Cc1ccc(-c2ccccc2C(=O)O)cc1 | null | null | null |
299,032 | ord_dataset-fb70ed83140e4f53a907d87192ad748c | null | 1994-01-01T00:11:00 | true | [CH3:1][N:2]1[C:10]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[C:4]2[C:11](=O)[CH2:12][CH2:13][C:3]1=2.Cl.[NH2:16][OH:17]>N1C=CC=CC=1>[CH3:1][N:2]1[C:10]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[C:4]2[C:11](=[N:16][OH:17])[CH2:12][CH2:13][C:3]1=2 | Cn1c2c(c3ccccc31)C(=O)CC2 | NO | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | c1ccncc1 | null | null | null | null | null | null | null | null | null | null | null | null | 3,4-Dihydro-4-methylcyclopent[b]indol-1(2H)-one (1.7 g) and hydroxylamine hydrochloride (1.925 g) in pyridine were heated at 60° for 18 h and cooled. The reaction mixture was evaporated in vacuo to a residue to which was added 8% sodium bicarbonate (150 ml). Extraction with ethyl acetate (300 ml) produced a suspension in the organic layer; this layer and associated solid was separated from the aqueous layer. The aqueous layer was re-extracted with ethyl acetate (250 ml). The combined organic extracts (and suspended solid) were evaporated to a residue, boiled with a mixture of ethanol (150 ml) and methanol (150 ml) and cooled to ca. 50°. The residue was adsorbed from this solution on to FCC silica and applied to an FCC column. Elution with ethyl acetate/3-10% methanol provided the title compound (1.69 g), m.p. 219°-224° (decomp.). | Cn1c2c(c3ccccc31)C(=NO)CC2 | null | 92 | null |
1,468,908 | ord_dataset-fd1fa959d6264608b0b7fcda16741bfd | null | 2014-01-01T00:08:00 | true | [OH:1][CH2:2][C:3]([CH3:7])([CH2:5][OH:6])[CH3:4].C1(C=CC(O)=CC=1)O.C[O-].[Na+].[C:19](OC)(=[O:23])[C:20]([CH3:22])=[CH2:21]>C1(C)C=CC=CC=1>[C:19]([O:1][CH2:2][C:3]([CH3:7])([CH3:4])[CH2:5][OH:6])(=[O:23])[C:20]([CH3:22])=[CH2:21] | C=C(C)C(=O)OC | CC(C)(CO)CO | null | C[O-] | Oc1ccc(O)cc1 | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Cc1ccccc1 | null | null | null | null | null | null | null | null | null | null | 62.5 | 1 | To a 2-L flask was charged neopentyl glycol (208.3 g, 2.0 moles), toluene (250 mL), hydroquinone (0.5 g) and sodium methoxide (25% in methanol, 8 g). The mixture was heated to 60-65° C. and methyl methacrylate (120 g, 1.2 moles) was added dropwise over 1 hour. The reaction was held at 70° C. for one hour under moderate vacuum to remove methanol and low boilers. Reaction was worked up by washing with 2×250 mL water and 1×100 mL saturated sodium chloride solution at 70° C. Toluene was evaporated and the resulting crude product (166 g) distilled to provide 3-hydroxy-2,2-dimethylpropyl methacrylate of 97% GC assay. To a 300 mL flask was charged 3-hydroxy-2,2-dimethylpropyl methacrylate (11.5 g, 0.064 moles), methylene chloride (20 g), DMAP (0.01 g), hydroquinone (0.05 g) and the mixture cooled to 0-5° C. To this was added dropwise diketene (5.4 g) at <3° C. Reaction allowed to warm to room temperature and stir overnight. Reaction cooled to 0-5° C. and additional diketene (2 g) added to complete reaction. Once reaction was complete, the dichloromethane was removed at 60° C. with house vacuum. Crude product distilled via Kugelrohr distillation to provide desired product of 92.6% assay with 1.6% starting material remaining (GC assay). | C=C(C)C(=O)OCC(C)(C)CO | null | null | null |
973,710 | ord_dataset-03ba810b7f464a06b5d8787af2e8b64e | null | 2010-01-01T00:06:00 | true | [OH:1][C:2]1[C:10]([O:11][CH3:12])=[CH:9][C:8]([C:13]2[N:14]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C:15]3[C:20]([CH:21]=2)=[CH:19][C:18]([CH:22]=O)=[CH:17][CH:16]=3)=[C:7]2[C:3]=1[CH2:4][NH:5][C:6]2=[O:31].[NH:32]1[CH2:36][CH2:35][CH2:34][CH2:33]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(#N)C>[OH:1][C:2]1[C:10]([O:11][CH3:12])=[CH:9][C:8]([C:13]2[N:14]([C:24]([O:26][C:27]([CH3:30])([CH3:28])[CH3:29])=[O:25])[C:15]3[C:20]([CH:21]=2)=[CH:19][C:18]([CH2:22][N:32]2[CH2:36][CH2:35][CH2:34][CH2:33]2)=[CH:17][CH:16]=3)=[C:7]2[C:3]=1[CH2:4][NH:5][C:6]2=[O:31] | COc1cc(-c2cc3cc(C=O)ccc3n2C(=O)OC(C)(C)C)c2c(c1O)CNC2=O | C1CCNC1 | null | CC(=O)O[BH-](OC(C)=O)OC(C)=O | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC#N | CC(=O)O | null | null | null | null | null | null | null | null | null | null | null | In a similar manner to Step 2 of Example 6, 4-hydroxy-5-methoxy-7-[1-(tert-butoxycarbonyl)-5-formylindol-2-yl]isoindolinone (0.582 g, 1.38 mmol) was dissolved in acetonitrile (15.0 mL), and the solution was treated with pyrrolidine (2.30 mL, 27.8 mmol), acetic acid (1.60 mL, 27.8 mmol) and sodium triacetoxyborohydride (0.876 g, 4.13 mmol), followed by purification by flash column chromatography (chloroform/methanol=85/15) to obtain 4-hydroxy-5-methoxy-7-[1-(tert-butoxycarbonyl)-5-(pyrrolidin-1-ylmethyl)indol-2-yl]isoindolinone (0.200 g, 30%). | COc1cc(-c2cc3cc(CN4CCCC4)ccc3n2C(=O)OC(C)(C)C)c2c(c1O)CNC2=O | null | 30.3 | null |
1,722,698 | ord_dataset-36057d699ac5449e9c37eb99abf78b03 | null | 2016-01-01T00:05:00 | true | Cl[C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[C:9]([Cl:17])[CH:10]=[CH:11][CH:12]=3)[C:7](=[O:18])[C:6]=2[CH:5]=[CH:4][CH:3]=1.[CH3:19][N:20]([CH3:24])[CH2:21][CH2:22][NH2:23]>CN(C)C(=O)C>[Cl:17][C:9]1[C:8]2[C:7](=[O:18])[C:6]3[C:15](=[C:2]([NH:23][CH2:22][CH2:21][N:20]([CH3:24])[CH3:19])[CH:3]=[CH:4][CH:5]=3)[C:14](=[O:16])[C:13]=2[CH:12]=[CH:11][CH:10]=1 | CN(C)CCN | O=C1c2cccc(Cl)c2C(=O)c2cccc(Cl)c21 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(=O)N(C)C | null | null | null | null | null | null | null | null | null | null | 25 | 1 | A mixture of 1,5-dichloro anthraquinone (5.0 g, 18.0 mmol), N,N-dimethylacetamide (30 mL) and N,N-dimethylethylenediamine (2 mL, 18 mmol) was stirred at room temperature for 1 hour and then heated in an oil bath (T=100° C.) for 45 minutes. Reaction mixture was cooled and filtered. To the filtrate petroleum ether (50 mL) was added and combined mixture was stirred at 4° C. over night. Precipitated solid was removed by filtration and supernatant was evaporated to dryness, co-evaporated with chloroform and dried under vacuum. The crude dye was then purified on Biotage SP4 system using a gradient of methanol in chloroform. Appropriate fractions were combined and evaporated to dryness to provide Compound 17 (1.0 g) as a red solid. Rf (9:1 CHCl3/MeOH): 0.46; Abs (max, PBS)=500 nm. The structure of Compound 17 is given below: | CN(C)CCNc1cccc2c1C(=O)c1cccc(Cl)c1C2=O | null | 16.9 | null |
1,622,145 | ord_dataset-35c51552812941cda45194a013d34bb9 | null | 2015-01-01T00:08:00 | true | C(OC([NH:8][C@H:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]1[NH:15][C:16]1[N:21]=[C:20]([C:22]2[S:26][C:25]([NH:27]C(=O)OC(C)(C)C)=[N:24][CH:23]=2)[C:19]2[C:35](=[O:49])[N:36](CC3C=CC(OC)=CC=3OC)[CH2:37][C:18]=2[C:17]=1[F:50])=O)(C)(C)C.[C:51]([OH:57])([C:53]([F:56])([F:55])[F:54])=[O:52]>>[NH2:8][C@H:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]1[NH:15][C:16]1[N:21]=[C:20]([C:22]2[S:26][C:25]([NH2:27])=[N:24][CH:23]=2)[C:19]2[C:35](=[O:49])[NH:36][CH2:37][C:18]=2[C:17]=1[F:50].[C:51]([OH:57])([C:53]([F:56])([F:55])[F:54])=[O:52] | COc1ccc(CN2Cc3c(F)c(N[C@@H]4CCCC[C@@H]4NC(=O)OC(C)(C)C)nc(-c4cnc(NC(=O)OC(C)(C)C)s4)c3C2=O)c(OC)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O=C(O)C(F)(F)F | null | null | null | null | null | null | null | null | null | null | null | null | A solution of tert-butyl (5-(6-(((1R,2S)-2-((tert-butoxycarbonyl)amino)cyclo-hexyl)amino)-2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-4-yl)-1,3-thiazol-2-yl)carbamate (41.5 mg, 0.058 mmol) in TFA (5 mL) was heated to 65° C. for 3 h. After removal of the solvent, the resulting crude material was reconstituted in MeOH/DMF (6.0 mL) and purified via preparative HPLC eluting with water (0.05% TFA) and ACN (10-20% gradient, 0.035% TFA). The collected fractions were stripped to dryness via rotary evaporation to yield the title compound as a TFA salt (6.7 mg, 32%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.12-2.11 (m, 9 H), 3.73 (br s, 2 H), 4.19 (d, J=3.79 Hz, 1 H), 4.41 (d, J=3.03 Hz, 2 H), 6.95 (d, J=3.03 Hz, 1 H), 7.77 (br s, 2 H), 8.44 (s, 1 H), 8.93 (s, 1 H). [M+H] calc'd for C16H19FN6OS, 363; found, 363. | Nc1ncc(-c2nc(N[C@@H]3CCCC[C@@H]3N)c(F)c3c2C(=O)NC3)s1 | null | null | null |
196,976 | ord_dataset-a58d1baeeea441fb9918c10f18f2cdb9 | null | 1989-01-01T00:09:00 | true | [N+:1]([C:4]1[CH:11]=[CH:10][C:7]([CH2:8][NH2:9])=[CH:6][CH:5]=1)([O-:3])=[O:2].C(N(CC)CC)C.[C:19](Cl)(=[O:22])[CH:20]=[CH2:21]>ClCCl>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([CH2:8][NH:9][C:19](=[O:22])[CH:20]=[CH2:21])=[CH:10][CH:11]=1)([O-:3])=[O:2] | NCc1ccc([N+](=O)[O-])cc1 | C=CC(=O)Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(CC)CC | ClCCl | null | null | null | null | null | null | null | null | null | null | 0.5 | A solution of freshly prepared 4-nitrobenzylamine (3.8 g) in dry dichloromethane (100 ml) containing triethylamine (3.5 ml) was added dropwise to acryloyl chloride (2.2 ml) in dry dichloromethane (100 ml), over 20 min during which time the temperature was kept between -15° and -7°. The reaction mixture was stirred at this temperature for 0.5 h. and then allowed to reach room temperature over a period of 1.25 h. The resulting solution was washed with 2N hydrochloric acid (50 ml), water (50 ml), aqueous 8% sodium bicarbonate solution, and water (50 ml), dried (MgSO4) and evaporated to dryness to afford a solid (3.89 g). This which was triturated with cyclohexane (about 400 ml) to give the title compound as a powder (3.654 g) m.p. 119°-121°. | C=CC(=O)NCc1ccc([N+](=O)[O-])cc1 | null | null | null |
851,433 | ord_dataset-171b840ae6e84e45bab43b987d09f5c7 | null | 2008-01-01T00:11:00 | true | Br[C:2]1[C:26](=[O:27])[N:25]([CH:28]2[CH2:32][CH2:31][CH2:30][CH2:29]2)[C:5]2[N:6]=[C:7]([NH:10][C:11]3[CH:16]=[CH:15][C:14]([N:17]4[CH2:22][CH:21]([CH3:23])[O:20][CH:19]([CH3:24])[CH2:18]4)=[CH:13][N:12]=3)[N:8]=[CH:9][C:4]=2[C:3]=1[CH3:33].C([Sn](CCCC)(CCCC)[C:39]([O:41][CH2:42][CH3:43])=[CH2:40])CCC>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:28]1([N:25]2[C:5]3[N:6]=[C:7]([NH:10][C:11]4[CH:16]=[CH:15][C:14]([N:17]5[CH2:18][CH:19]([CH3:24])[O:20][CH:21]([CH3:23])[CH2:22]5)=[CH:13][N:12]=4)[N:8]=[CH:9][C:4]=3[C:3]([CH3:33])=[C:2]([C:39]([O:41][CH2:42][CH3:43])=[CH2:40])[C:26]2=[O:27])[CH2:29][CH2:30][CH2:31][CH2:32]1 | Cc1c(Br)c(=O)n(C2CCCC2)c2nc(Nc3ccc(N4CC(C)OC(C)C4)cn3)ncc12 | C=C(OCC)[Sn](CCCC)(CCCC)CCCC | null | c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Cc1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | null | 6-Bromo-8-cyclopentyl-2-[5-(2,6-dimethyl-morpholin-4-yl)-pyridin-2-ylamino]-5-methyl-8H-pyrido[2,3-d]pyrimidin-7-one (0.062 g, 0.121 mmol), tetrakis(triphenylphosphine)palladium (0.017 g, 0.015 mmol) and tributyl-(1-ethoxy-vinyl)-stannane (0.068 mg, 0.188 mmol) were dissolved in toluene (2 mL) and slowly brought to reflux for 12 hours. Additional tetrakis(triphenylphosphine)palladium (0.010 g) was added and the reaction brought to reflux for 16 hours. The reaction mixture was cooled and purified by silica gel chromatography to 8-cyclopentyl-2-[5-(2,6-dimethyl-morpholin-4-yl)-pyridin-2-ylamino]-6-(1-ethoxy-vinyl)-5-methyl-8H-pyrido[2,3-d]pyrimidin-7-one as a yellow solid (0.055 g, 90.2%). 1H NMR δ(400 MHz, CDCl3) 8.72 (s, 1H), 8.17 (d, J=9.0 Hz, 1H), 7.99 (d, J=2.9 Hz, 1H), 7.83 (s, 1H), 7.29 (dd, J=2.9, 9.0 Hz, 1H), 5.89 (m, 1H), 4.51 (d, J=2.5 Hz, 1H), 4.17 (d, J=2.4 Hz, 1H), 3.93 (q, J=7.1 Hz, 2H), 3.83 (m, 2H), 3.37 (d, J=10.3 Hz, 2H), 2.44 (dd, J=10.5, 10.5, 2H), 2.41 (s, 3H), 2.34 (m, 2H), 2.06 (m, 2H), 1.84 (m, 2H), 1.65 (m, 2H), 1.36 (t, J=7.1 Hz, 3H), 1.26 (d, J=6.4 Hz, 6H). | C=C(OCC)c1c(C)c2cnc(Nc3ccc(N4CC(C)OC(C)C4)cn3)nc2n(C2CCCC2)c1=O | null | null | null |
1,513,313 | ord_dataset-8c74302143c04eb9983e4b3a7ead2d72 | null | 2014-01-01T00:12:00 | true | [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9]([C:12]1[N:13]([C:21]2[CH:26]=[CH:25][C:24]([C:27]3[CH:32]=[C:31](S(C)(=O)=O)[C:30]([CH2:37][OH:38])=[C:29]([F:39])[CH:28]=3)=[CH:23][C:22]=2[F:40])[CH:14]=[C:15]([C:17]([OH:20])([CH3:19])[CH3:18])[N:16]=1)([CH3:11])[CH3:10].[C:41]([O:45][P:46]([O:53][CH2:54][C:55]1[CH:56]=[C:57]([CH:61]=[CH:62][CH:63]=1)[C:58](O)=[O:59])([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])([CH3:44])([CH3:43])[CH3:42].C1CCC(N=C=NC2CCCCC2)CC1>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:49]([O:48][P:46]([O:53][CH2:54][C:55]1[CH:56]=[C:57]([CH:61]=[CH:62][CH:63]=1)[C:58]([O:38][CH2:37][C:30]1[CH:31]=[CH:32][C:27]([C:24]2[CH:25]=[CH:26][C:21]([N:13]3[CH:14]=[C:15]([C:17]([OH:20])([CH3:19])[CH3:18])[N:16]=[C:12]3[C:9]([C:3]3[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][C:4]=3[Cl:8])([CH3:11])[CH3:10])=[C:22]([F:40])[CH:23]=2)=[CH:28][C:29]=1[F:39])=[O:59])([O:45][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:47])([CH3:50])([CH3:51])[CH3:52] | CC(C)(C)OP(=O)(OCc1cccc(C(=O)O)c1)OC(C)(C)C | CC(C)(O)c1cn(-c2ccc(-c3cc(F)c(CO)c(S(C)(=O)=O)c3)cc2F)c(C(C)(C)c2c(Cl)cccc2Cl)n1 | null | C(=NC1CCCCC1)=NC1CCCCC1 | 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 | 25 | 15 | To a stirred solution of 2-(2-(2-(2,6-dichlorophenyl)propan-2-yl)-1-(3,3′-difluoro-4′-(hydroxymethyl)-5′-(methylsulfonyl)biphenyl-4-yl)-1H-imidazol-4-yl)propan-2-ol (prepared in the manner described in PCT Publication No. WO 2010/138598, 0.1 g, 0.16 mmol) in CH2Cl2 (2 mL) was added 3-((di-tert-butoxyphosphoryloxy)methyl)benzoic acid (140 mg, 0.40 mmol), DMAP (4 mg, 0.33 mmol) and DCC (86 mg, 0.42 mmol). The reaction mixture was stirred at rt. After 15 h, the reaction mixture was filtered, washed with CH2Cl2 (2×10 mL), and the solvents were removed under reduced pressure to yield the crude material. The crude product was purified by column chromatography (basic alumina, EtOAc:Hexane) to afford (4′-(2-(2-(2,6-dichlorophenyl)propan-2-yl)-4-(2-hydroxypropan-2-yl)-1H-imidazol-1-yl)-3,3′-difluorobiphenyl-4-yl)methyl 3-((di-tert-butoxyphosphoryloxy)methyl)benzoate (95 mg, 0.10 mmol, 62%). LCMS: (Ascentis Express C8 (50×2.1 mm-2.7 μm); Solvent A=10 mM NH4COOH in 98% H2O and 2% acetonitrile; Solvent B=98% acetonitrile and 2% 10 mM NH4COOH in H2O; gradient 0% (1.5 min) then to 100% (1.5-3.2 min), 100% (3.2-4 min) B over 4 min), retention time: 2.22 min; LCMS (MM-ES+APCI), flow 1 mL/min, m/z 937.2. | CC(C)(C)OP(=O)(OCc1cccc(C(=O)OCc2ccc(-c3ccc(-n4cc(C(C)(C)O)nc4C(C)(C)c4c(Cl)cccc4Cl)c(F)c3)cc2F)c1)OC(C)(C)C | null | 62 | null |
1,611,518 | ord_dataset-9cecb3a8d3b9494191b28dcefea66af2 | null | 2015-01-01T00:07:00 | true | [O:1]1[CH2:6][CH:5]=[C:4]([C:7]2[CH:8]=[CH:9][C:10]([NH2:13])=[N:11][CH:12]=2)[CH2:3][CH2:2]1>C(O)C>[O:1]1[CH2:6][CH2:5][CH:4]([C:7]2[CH:8]=[CH:9][C:10]([NH2:13])=[N:11][CH:12]=2)[CH2:3][CH2:2]1 | Nc1ccc(C2=CCOCC2)cn1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | null | null | null | null | null | null | null | null | null | null | null | null | The title compound was prepared as described in example 61, substituting tert-butyl-6-[3-(8-fluoro-quinolin-4-yl)-ureido]-3′,6′-dihydro-2′H-[2,4′]bipyridinyl-1′-carboxylate by 5-(3,6-dihydro-2H-pyran-4-yl)pyridin-2-amine and by using ethanol as solvent. | Nc1ccc(C2CCOCC2)cn1 | null | null | null |
1,702,785 | ord_dataset-54347fcace774f89850681d6dec8009f | null | 2016-01-01T00:03:00 | true | [CH3:1][C@H:2]1[CH2:6][CH2:5][CH2:4][N:3]1[C:7]([C:9]1[N:17]2[C:12]([CH2:13][O:14][CH2:15][CH2:16]2)=[C:11]([C:18](O)=[O:19])[CH:10]=1)=[O:8].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.Cl.[NH2:44][C@@H:45]([C:48]1[CH:55]=[CH:54][C:51]([C:52]#[N:53])=[C:50]([Cl:56])[CH:49]=1)[CH2:46][CH3:47].C(N(CC)CC)C>CN(C)C=O>[Cl:56][C:50]1[CH:49]=[C:48]([C@H:45]([NH:44][C:18]([C:11]2[CH:10]=[C:9]([C:7]([N:3]3[CH2:4][CH2:5][CH2:6][C@@H:2]3[CH3:1])=[O:8])[N:17]3[CH2:16][CH2:15][O:14][CH2:13][C:12]=23)=[O:19])[CH2:46][CH3:47])[CH:55]=[CH:54][C:51]=1[C:52]#[N:53] | C[C@H]1CCCN1C(=O)c1cc(C(=O)O)c2n1CCOC2 | CC[C@@H](N)c1ccc(C#N)c(Cl)c1 | null | CCN=C=NCCCN(C)C | Cl | On1nnc2ccccc21 | 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 | 50 | 2 | To a solution of 6-((S)-2-methyl-pyrrolidine-1-carbonyl)-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-8-carboxylic acid (Comp. No. 7c) (75 mg, 0.270 mmol) in dimethylformamide (2 ml) was added 1-hydroxybenzotriazole (41 mg, 0.30 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (58 mg, 0.30 mmol). The mixture was stirred for 2 h at 50° C., then 4-((R)-1-amino-propyl)-2-chloro-benzonitrile hydrochloride (68 mg, 0.3 mmol) and triethylamine (60 mg, 0.6 mmol) were added and the mixture was stirred at 25° C. overnight. The mixture was filtered through a small filter cartridge and the solution was purified by reverse phase HPLC (acetonitrile/water gradient with 0.1% trifluoroacetic acid) to give 82 mg (67%) of 6-((S)-2-methyl-pyrrolidine-1-carbonyl)-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-8-carboxylic acid [(R)-1-(3-chloro-4-cyano-phenyl)-propyl]-amide as white solid. LC/MS (method 2): Rt=1.24 min; m/z=455.08 (M+H+). 1H-NMR: δ (ppm)=8.20 (1H, d), 7.94 (1H, d), 7.70 (1H, s), 7.50 (1H, d), 7.24 (1H, s), 4.95 (1H, d), 4.82-4.92 (2H, m), 4.20-4.29 (2H, m), 3.70-4.00 (5H, m), 2.07 (1H, m), 1.97 (1H, m), 1.74-1.85 (3H, m), 1.57 (1H, m), 1.19 (3H, d), 0.89 (3H, t). | CC[C@@H](NC(=O)c1cc(C(=O)N2CCC[C@@H]2C)n2c1COCC2)c1ccc(C#N)c(Cl)c1 | null | 67 | null |
1,009,707 | ord_dataset-7448b89163bf426c9d9777809ce24cec | null | 2010-01-01T00:11:00 | true | [CH3:1][CH:2]([N:4]1[CH:8]([CH3:9])[CH2:7][C:6](=[O:10])[NH:5]1)[CH3:3].OO.O.[OH-].[Na+]>C(O)(=O)C>[CH3:1][CH:2]([N:4]1[C:8]([CH3:9])=[CH:7][C:6](=[O:10])[NH:5]1)[CH3:3] | CC(C)N1NC(=O)CC1C | null | null | OO | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CC(=O)O | null | null | null | null | null | null | null | null | null | 22.5 | 15 | 1-(1-methylethyl)-5-methyl-3-pyrazolidinone (390 g; 2.74 mol) is dissolved in acetic acid (170 ml) with warming. 35% aqueous hydrogen peroxide (260 ml; 3.0 mol) is added within 3 h while keeping the temperature at about 65° C. The reaction mixture is then stirred at about 20 to 25° C. for 15 h. Water (1.2 L) is then added and the pH of the mixture is adjusted to about 7 by means of addition of approx. 1 L 50%-weight aqueous sodium hydroxide solution. Upon cooling to 5° C. the reaction mixture is filtered. The product is washed with water and dried at about 50° C. Colourless crystals are obtained. | Cc1cc(=O)[nH]n1C(C)C | null | null | null |
912,558 | ord_dataset-c663259b80f947e2a8923796fb0e9a6b | null | 2009-01-01T00:10:00 | true | [Cl:1][C:2]1[C:3]2[S:10][CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Li+].CC([N-]C(C)C)C.[CH3:19][S:20](=S)(OC)=O>C1COCC1>[Cl:1][C:2]1[C:3]2[S:10][C:9]([S:20][CH3:19])=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1 | Clc1ncnc2ccsc12 | COS(C)(=O)=S | null | CC(C)[N-]C(C)C | [Li+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | -78 | 0.5 | To a suspension of compound 6.2 (5 mmol) in dry THF (25 mL) was added LDA (6 mmol, 2.0 M in heptane/THF/ethylbenzene) at −78° C. under an atmosphere of N2. After stirring at −78° C. for 30 minutes, the mixture was transferred to a pre-cooled solution of methyl methanethiosulfonate (8 mmol) in of dry THF (10 mL) at −78° C. The resulting mixture was slowly warmed to room temperature and stirred for 2 hours. The reaction was quenched by the addition of several portions of sat. aq. NH4Cl, concentrated and partitioned between EtOAc and saturated aqueous NaHCO3. The organic layer was separated, dried and concentrated to give a residue that was purified by flash column chromatography on silica gel to give 4-chloro-6-methylsulfanyl-thieno[3,2-d]pyrimidine (compound 63.1). | CSc1cc2ncnc(Cl)c2s1 | null | null | null |
1,241,436 | ord_dataset-c544c0c663f54dbea4ddb52ddde7934e | null | 2013-01-01T00:01:00 | true | C[O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([S:9]([CH3:12])(=[O:11])=[O:10])[CH:4]=1>Br.C(O)(=O)C>[CH3:12][S:9]([C:5]1[CH:4]=[C:3]([OH:2])[CH:8]=[CH:7][CH:6]=1)(=[O:10])=[O:11] | COc1cccc(S(C)(=O)=O)c1 | null | null | Br | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(=O)O | null | null | null | null | null | null | null | null | null | null | 25 | null | 1-Methoxy-3-(methylsulfonyl)benzene (300 mg, 1.61 mmol) was suspended in 1.6 mL aqueous hydrobromic acid (48% w/w) and 1.6 mL acetic acid. The mixture was heated under reflux for 24 hours. The reaction was cooled back to room temperature and concentrated. The residue was purified by column chromatography through a 40 gram biotage silica gel cartridge eluting with 40-70% ethyl acetate/hexanes (gradient) to give the product as white solid. LRMS calc: 172.0; obs: 173.2 (M+1). | CS(=O)(=O)c1cccc(O)c1 | null | null | null |
1,684,699 | ord_dataset-3953983e052a4076aa7cc0880b79cb8b | null | 2016-01-01T00:01:00 | true | [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[C:4]=1[CH:11]1[NH:16][C:15](=[O:17])[CH2:14][CH2:13][CH2:12]1.Br[CH2:19][C:20]1[CH:30]=[CH:29][C:23]2[O:24][C:25]([F:28])([F:27])[O:26][C:22]=2[CH:21]=1>>[F:28][C:25]1([F:27])[O:24][C:23]2[CH:29]=[CH:30][C:20]([CH2:19][N:16]3[CH:11]([C:4]4[C:5]([O:9][CH3:10])=[CH:6][CH:7]=[CH:8][C:3]=4[O:2][CH3:1])[CH2:12][CH2:13][CH2:14][C:15]3=[O:17])=[CH:21][C:22]=2[O:26]1 | COc1cccc(OC)c1C1CCCC(=O)N1 | FC1(F)Oc2ccc(CBr)cc2O1 | null | null | null | null | null | null | null | 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 described general procedure 4 (GP4) by reaction of 6-(2,6-dimethoxyphenyl)piperidin-2-one with 5-(bromomethyl)-2,2-difluorobenzo[d][1,3]dioxole. Subsequent purification by preparative HPLC afforded the target compound. LC-MS (conditions A): tR=0.91 min.; [M+H]+: 406.17 g/mol. | COc1cccc(OC)c1C1CCCC(=O)N1Cc1ccc2c(c1)OC(F)(F)O2 | null | null | null |
812,675 | ord_dataset-892acf7477db4d3a8a8559f004a7c0a2 | null | 2008-01-01T00:03:00 | true | [F:1][C:2]([F:42])([F:41])[C:3]1[CH:4]=[C:5]([C@H:13]([O:15][C@H:16]2[CH2:21][CH2:20][C@@H:19]([CH2:22]CS([O-])(=O)=O)[C@@H:18]([CH2:28]CS([O-])(=O)=O)[C@@H:17]2[C:34]2[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=2)[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH2:43]([NH2:50])[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>C(O)C>[CH2:43]([N:50]1[CH2:28][C@@H:18]2[C@H:19]([CH2:20][CH2:21][C@H:16]([O:15][C@@H:13]([C:5]3[CH:6]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:8]=[C:3]([C:2]([F:42])([F:41])[F:1])[CH:4]=3)[CH3:14])[C@H:17]2[C:34]2[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=2)[CH2:22]1)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1 | C[C@@H](O[C@H]1CC[C@@H](CCS(=O)(=O)[O-])[C@@H](CCS(=O)(=O)[O-])[C@@H]1c1ccc(F)cc1)c1cc(C(F)(F)F)cc(C(F)(F)F)c1 | NCc1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | null | null | null | null | null | null | null | null | null | null | 150 | null | In a pressure tube was placed a solution of crude [(1S,2R,3R,4S)-4-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-3-(4-fluorophenyl)cyclohexane-1,2-diyl]di(methylene) dimethanesulfonate (step H) in ˜20 mL ethanol and 1.2 mL (˜3 equiv.) benzylamine. The pressure tube was sealed and heated at 150° C. in an oil bath for 3 hr. The tube was cooled to RT and opened. The resulting mixture was transferred to a round bottom flask and the solvent removed under vacuum. The residue was diluted with 100 mL EtOAc, washed with 20 mL 5N aq. NaOH, dried over MgSO4 drying agent, filtered and the solvent was evaporated under vacuum. The residue was purified by flash column chromatography on silica gel eluting with EtOAc to give 1.6 g of the title compound. 1H-NMR (CDCl3): δ: 7.35-7.20 (5 H, m), 7.50 (2 H, s), 6.97 (2 H, m), 6.85 (2 H, t, J=8.2 Hz), 4.42 (1 H, t, J=6.0 Hz), 3.75 (2 H, d, J=13.4 Hz), 3.50 (2 H, d, J=13.4 Hz), 3.30 (1 H, m), 2.96 (1 H, m), 2.52 (3 H, m), 2.19 (2 H, m), 1.98 (1 H, m), 1.97 (1 H, m), 1.86 (2 H, m), 1.57 (1 H, m), 1.33 (3 H, t, J=6.0 Hz), 1.30 (1 H, m). MS: (MH)+ 566.0. | C[C@@H](O[C@H]1CC[C@@H]2CN(Cc3ccccc3)C[C@H]2[C@@H]1c1ccc(F)cc1)c1cc(C(F)(F)F)cc(C(F)(F)F)c1 | null | null | null |
1,198,361 | ord_dataset-fb72428f30234761b4216139dc228d0c | null | 2012-01-01T00:09:00 | true | [CH:1]1([CH2:6][CH:7]([N:11]2[C:16](=[O:17])[CH:15]=[C:14]([OH:18])[CH:13]=[N:12]2)[C:8]([OH:10])=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.S(Cl)(Cl)=O.[CH3:23]O>>[CH3:23][O:9][C:8](=[O:10])[CH:7]([N:11]1[C:16](=[O:17])[CH:15]=[C:14]([OH:18])[CH:13]=[N:12]1)[CH2:6][CH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1 | O=C(O)C(CC1CCCC1)n1ncc(O)cc1=O | CO | 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 | 25 | null | A solution of 3-cyclopentyl-2-(4-hydroxy-6-oxo-6H-pyridazin-1-yl)-propionic acid (12.5 g, 47.6 mmol) in methanol (150 mL) was treated dropwise with thionyl chloride (7.1 g, 59.5 mmol). The mixture was stirred at reflux for 1 h. At this time, the reaction was cooled to 25° C. and concentrated in vacuo. The resulting residue was partitioned between water and ethyl acetate. The combined organics were dried over sodium sulfate and concentrated in vacuo to afford 3-cyclopentyl-2-(4-hydroxy-6-oxo-6H-pyridazin-1-yl)-propionic acid methyl ester as a light yellow oil (10.5 g, 80%). | COC(=O)C(CC1CCCC1)n1ncc(O)cc1=O | null | 80 | null |
1,746,144 | ord_dataset-60a3e71da3174666a50a61dcfa611a9f | null | 2016-01-01T00:07:00 | true | [NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C@H:9]([C:11]2[N:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:15](=[O:23])[C:14]3=[C:24]([CH3:27])[CH:25]=[CH:26][N:13]3[N:12]=2)[CH3:10])[C:3]=1Br.[CH2:29]([O:31][C:32]1[C:37]([NH:38][S:39]([C:42]2[CH:47]=[CH:46][C:45]([OH:48])=[CH:44][CH:43]=2)(=[O:41])=[O:40])=[CH:36][C:35](B2OC(C)(C)C(C)(C)O2)=[CH:34][N:33]=1)[CH3:30].C(=O)([O-])[O-].[Na+].[Na+]>>[NH2:1][C:2]1[C:3]([C:35]2[CH:36]=[C:37]([NH:38][S:39]([C:42]3[CH:43]=[CH:44][C:45]([OH:48])=[CH:46][CH:47]=3)(=[O:41])=[O:40])[C:32]([O:31][CH2:29][CH3:30])=[N:33][CH:34]=2)=[C:4]([NH:8][C@H:9]([C:11]2[N:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:15](=[O:23])[C:14]3=[C:24]([CH3:27])[CH:25]=[CH:26][N:13]3[N:12]=2)[CH3:10])[N:5]=[CH:6][N:7]=1 | Cc1ccn2nc([C@H](C)Nc3ncnc(N)c3Br)n(-c3ccccc3)c(=O)c12 | CCOc1ncc(B2OC(C)(C)C(C)(C)O2)cc1NS(=O)(=O)c1ccc(O)cc1 | null | O=C([O-])[O-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | (S)-2-(1-((6-Amino-5-bromopyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (54 mg, 0.12 mmol) was treated with N-(2-ethoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)-4-hydroxybenzenesulfonamide (116 mg, 0.18 mmol), sodium carbonate (30 mg, 0.28 mmol) and 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (32 mg, 0.04 mmol) according to the method described in Example 3 to give 22 mg (27% yield) of the title compound. Purity 100%. LRMS (m/z): 654 (M+1)+. 1H NMR (400 MHz, CD3OD δ 7.88 (m, 1H), 7.79 (s, 1H), 7.71 (s, 1H), 7.65-7.42 (m, 7H), 7.38 (dd, J=7.6, 1.2 Hz, 2H), 6.76 (d, J=8.8 Hz, 2H), 6.33 (m, 1H), 4.23 (q, J=6.9 Hz, 2H), 2.42 (s, 3H), 1.30 (d, J=6.8 Hz, 3H), 1.25 (t, J=7.1 Hz, 3H). | CCOc1ncc(-c2c(N)ncnc2N[C@@H](C)c2nn3ccc(C)c3c(=O)n2-c2ccccc2)cc1NS(=O)(=O)c1ccc(O)cc1 | null | 28 | null |
1,442,482 | ord_dataset-275a3da8f45f4536ad29727f0ef9ba66 | null | 2014-01-01T00:06:00 | true | C[O:2][C:3](=[O:35])[CH2:4][N:5]1[CH2:10][CH2:9][C:8]([CH2:19][NH:20][C:21]([NH2:34])=[N:22][C:23]([C:25]2[C:30]([NH2:31])=[N:29][C:28]([NH2:32])=[C:27]([Cl:33])[N:26]=2)=[O:24])([CH2:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:7][CH2:6]1.Cl>CO.[OH-].[Na+]>[NH2:31][C:30]1[C:25]([C:23]([N:22]=[C:21]([NH2:34])[NH:20][CH2:19][C:8]2([CH2:11][CH2:12][C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH2:7][CH2:6][N:5]([CH2:4][C:3]([OH:35])=[O:2])[CH2:10][CH2:9]2)=[O:24])=[N:26][C:27]([Cl:33])=[C:28]([NH2:32])[N:29]=1 | COC(=O)CN1CCC(CCc2ccccc2)(CNC(N)=NC(=O)c2nc(Cl)c(N)nc2N)CC1 | null | null | Cl | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | 50 | 1 | A mixture of 145 mg (0.23 mmol) {4-[N′-(3,5-diamino-6-chloro-pyrazine-2-carbonyl)-guanidinomethyl]-4-phenethyl-piperidin-1-yl}-acetic acid methyl ester (Example 1.16) in 5 ml methanol and 235 μl 4 N NaOH is stirred at 50° C. for 1 hour. Then the solution is acidified with 470 μl 4 N HCl and concentrated under reduced pressure. The residue is purified by preparative reverse phase HPLC (gradient of acetonitrile and water+0.2% trifluoroacetic acid, 25° C.). Fractions containing the title compound were concentrated under reduced pressure. | NC(=NC(=O)c1nc(Cl)c(N)nc1N)NCC1(CCc2ccccc2)CCN(CC(=O)O)CC1 | null | null | null |
1,295,692 | ord_dataset-de51ecc8d4434bacaa8bc32d7d73484c | null | 2013-01-01T00:05:00 | true | [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:14]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:17]([NH2:24])=[CH:16][CH:15]=2)=[CH:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>CO.[Pd]>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([C:14]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:17]([NH2:24])=[CH:16][CH:15]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3] | CC(C)(C)OC(=O)N1CC=C(c2ccc(N)c3ccccc23)CC1 | null | null | [Pd] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | null | null | To a solution of tert-butyl-4-(4-aminonaphthalen-1-yl)-5,6-dihydropyridine-1(2H)-carboxylate in 50 mL of MeOH was added 10 wt % Pd—C (100 mg). The reaction was degassed to remove air and stirred under 1 atm. H2 until the starting material is consumed. The Pd—C was removed by filtration and the resulting solution was concentrated in vacuo to afford tert-butyl-4-(4-aminonaphthalen-1-yl)piperidine-1-carboxylate. | CC(C)(C)OC(=O)N1CCC(c2ccc(N)c3ccccc23)CC1 | null | null | null |
268,885 | ord_dataset-a20aed058d7b40bc81fdf50bc5b03f97 | null | 1993-01-01T00:06:00 | true | Br[CH:2]1[CH2:7][CH2:6][O:5][N:4]([CH3:8])[C:3]1=[O:9].[CH3:10][C:11]([C:14]1[C:19]([OH:20])=[C:18]([C:21]([CH3:24])([CH3:23])[CH3:22])[N:17]=[C:16]([CH:25]=[O:26])[N:15]=1)([CH3:13])[CH3:12]>C1(C)C=CC=CC=1.ClCCl.[Zn]>[CH3:13][C:11]([C:14]1[C:19]([OH:20])=[C:18]([C:21]([CH3:24])([CH3:23])[CH3:22])[N:17]=[C:16]([CH:25]([OH:26])[CH:2]2[CH2:7][CH2:6][O:5][N:4]([CH3:8])[C:3]2=[O:9])[N:15]=1)([CH3:10])[CH3:12] | CN1OCCC(Br)C1=O | CC(C)(C)c1nc(C=O)nc(C(C)(C)C)c1O | null | [Zn] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | Cc1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | A mixture of 1.1 g (5.7 mmol) of 4-bromo tetrahydro-2-methyl 2H 1,2-oxazin-3-one, Example 1, 1.2 g (5.1 mmol) of 4,6-bis(1,1-dimethylethyl)-5-hydroxy-2-pyrimidinecarboxaldehyde, Example 6, and 0.75 g (11 mmol) of zinc dust in 30 mL of toluene was stirred at reflux for 18 hours. The cooled reaction mixture was diluted with dichloromethane and vigorously stirred. The zinc was filtered and washed with dichloromethane. The combined filtrates were evaporated to a foam. The residue was purified by flash chromatography (silica gel, 15% ethyl acetate in hexane elution) to give 0.70 g (39%) of the title compound as an oil mixture of diastereomers; MS m/e 352 (M+ 1). | CN1OCCC(C(O)c2nc(C(C)(C)C)c(O)c(C(C)(C)C)n2)C1=O | null | 39.1 | null |
841,087 | ord_dataset-074f86301ec5441ab3b52d902ac06949 | null | 2008-01-01T00:09:00 | true | [CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]([CH:11]=O)=[CH:9][CH:10]=1)=[O:5])[CH3:2].Cl.[NH2:14][OH:15].C(O)C.C([O-])(=O)C.[Na+]>O>[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]([CH:11]=[N:14][OH:15])=[CH:9][CH:10]=1)=[O:5])[CH3:2] | CCOC(=O)c1ccc(C=O)[nH]1 | NO | null | CC(=O)[O-] | Cl | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CCO | null | null | null | null | null | null | null | null | null | 90 | 0.5 | A mixture of 5-formyl-1H-pyrrole-2-carboxylic acid ethyl ester (as prepared in the previous step, 300 mg, 1.80 mmol), hydroxylamine hydrochloride (560 mg, 8.10 mmol), ethanol (10 mL), sodium acetate (1.10 g, 13.4 mmol) and water (10 mL) was stirred at 90° C. for 30 min. The solvents were removed in vacuo and the solid was collected on a Buchner funnel and washed with water (10 mL) to yield 226 mg (69%) of the title compound as a white solid: LC-MS (ESI, m/z): Calcd. for C8H11N2O3, 183.1 (M+H); found: 183.0. | CCOC(=O)c1ccc(C=NO)[nH]1 | null | 69 | null |
750,090 | ord_dataset-844a22e1fcab44a5b59c5e2922b2855a | null | 2007-01-01T00:01:00 | true | [C:1]([NH:4][C:5]1[CH:17]=[C:16]2[C:8]([C:9]3[C:14]([CH2:18][CH2:19][CH2:20][CH3:21])([CH2:15]2)[CH2:13][CH2:12][C:11](=[O:22])[CH:10]=3)=[CH:7][C:6]=1[F:23])(=[O:3])[CH3:2].[Br:24]N1C(=O)CCC1=O>C(Cl)Cl>[C:1]([NH:4][C:5]1[CH:17]=[C:16]2[C:8]([C:9]3[C:14]([CH2:18][CH2:19][CH2:20][CH3:21])([CH2:15]2)[CH2:13][CH2:12][C:11](=[O:22])[C:10]=3[Br:24])=[CH:7][C:6]=1[F:23])(=[O:3])[CH3:2] | O=C1CCC(=O)N1Br | CCCCC12CCC(=O)C=C1c1cc(F)c(NC(C)=O)cc1C2 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | null | 1 | The product from step 1 (1.1 g, approx. 3.5 mmol) was dissolved in anhydrous CH2Cl2 (11 mL) and the solution was purged with N2, cooled in an ice bath, and treated with N-bromosuccinimide (0.498 g, 2.8 mmol). After stirring at 0–5° C. for one hour, the reaction mixture was partitioned between water (150 mL) and EtOAc (150 mL). The organic portion was washed with aqueous 5% NaHCO3 and brine, dried over MgSO4, filtered, and evaporated under vacuum to provide crude 7-(acetylamino)-4-bromo-9a-butyl-6-fluoro-1,2,9,9a-tetrahydro-3H-fluoren-3-one (1.35 g). | CCCCC12CCC(=O)C(Br)=C1c1cc(F)c(NC(C)=O)cc1C2 | null | 122.3 | null |
1,435,587 | ord_dataset-275a3da8f45f4536ad29727f0ef9ba66 | null | 2014-01-01T00:06:00 | true | COC1C=C(OC)C=CC=1C[N:6]([C:19]1[S:20][CH:21]=[CH:22][N:23]=1)[S:7]([C:10]1[CH:18]=[CH:17][C:13]([C:14]([OH:16])=O)=[CH:12][CH:11]=1)(=[O:9])=[O:8].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC.C(Cl)Cl.[Cl:64][C:65]1[CH:66]=[C:67]([CH:70]=[CH:71][C:72]=1[Cl:73])[CH2:68][NH2:69]>>[Cl:64][C:65]1[CH:66]=[C:67]([CH:70]=[CH:71][C:72]=1[Cl:73])[CH2:68][NH:69][C:14](=[O:16])[C:13]1[CH:12]=[CH:11][C:10]([S:7]([NH:6][C:19]2[S:20][CH:21]=[CH:22][N:23]=2)(=[O:8])=[O:9])=[CH:18][CH:17]=1 | NCc1ccc(Cl)c(Cl)c1 | COc1ccc(CN(c2nccs2)S(=O)(=O)c2ccc(C(=O)O)cc2)c(OC)c1 | null | CN(C)C(On1nnc2ccccc21)=[N+](C)C | F[P-](F)(F)(F)(F)F | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(CC)CC | ClCCl | null | null | null | null | null | null | null | null | null | null | 8 | 4-{[(2,4-Dimethoxybenzyl)(1,3-thiazol-2-yl)amino]sulfonyl}benzoic acid (Preparation 99, 1.30E3 mg, 0.00300 mol), HBTU (1400.8 mg, 0.0031671 mol) and Et3N (1.07 mL, 0.00766 mol) were mixed in methylene chloride (10 mL, 0.2 mol). 3,4-dichlorobenzylamine (457.3 mg, 0.002598 mol) was added and the reaction stirred overnight. The reaction was washed with saturated sodium bicarbonate (aq). The organic phase was separated and dried over magnesium sulfate, the solvent was removed in vacuo to give an oily residue. The residue was purified by column chromatography (40 g silica gel column, hexanes to 50% ethyl acetate-hexanes gradient elution). Product fractions were combined and evaporated to give 1.13 g of the protected benzamide intermediate. The residue was dissolved in DCM and TFA was added dropwise until wet pH paper turned acidic when held above the reaction. After 30 minutes of stirring at room temperature, the solid precipitate was collected by filtration. The solid was rinsed with DCM, then ethyl ether. The solid was dissolved in 0.5N NaOH (5 mL) and filtered. The filtrate was washed 2× with ethyl ether, then treated with activated carbon and filtered through Celite. The pale yellow filtrate was acidified to pH 2 with 6N HCl. The white precipitate was collected by filtration and rinsed with water then ethyl ether. Vacuum drying yielded 446 mg of product as a white powder. | O=C(NCc1ccc(Cl)c(Cl)c1)c1ccc(S(=O)(=O)Nc2nccs2)cc1 | null | 98.3 | null |
414,522 | ord_dataset-275344fd078b4340b89ca0b6e92beb95 | null | 1998-01-01T00:10:00 | true | [CH2:1]([NH:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:16]([O:20][CH3:21])(=[O:19])[CH:17]=[CH2:18]>CO>[CH2:9]([N:8]([CH2:18][CH2:17][C:16]([O:20][CH3:21])=[O:19])[CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1 | c1ccc(CNCc2ccccc2)cc1 | C=CC(=O)OC | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | null | null | A! Starting from dibenzylamine (48.7 ml, 0.25 mole) and methyl acrilate (112.5 ml, 1.25 moles) in 259 ml of methanol, and following the procedure of Example 15,A!, there were obtained 70 g (yield: 99%) of methyl 3-(N,N-dibenzylamino)-propanoate which was used as such in the next step. | COC(=O)CCN(Cc1ccccc1)Cc1ccccc1 | null | 98.8 | null |
71,884 | ord_dataset-520610070b3c4780a03b44c7fcecc28f | null | 1980-01-01T00:10:00 | true | [NH2:1][CH:2]([C:6]1[CH:11]=[CH:10][C:9]([OH:12])=[C:8]([CH2:13]Cl)[CH:7]=1)[C:3]([OH:5])=[O:4].[S-:15][C:16]#[N:17].[K+]>CO>[NH2:1][CH:2]([C:6]1[CH:11]=[CH:10][C:9]([OH:12])=[C:8]([CH2:13][S:15][C:16]#[N:17])[CH:7]=1)[C:3]([OH:5])=[O:4] | N#C[S-] | NC(C(=O)O)c1ccc(O)c(CCl)c1 | null | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | null | null | A solution of (-)-α-amino-3-(chloromethyl)-4-hydroxybenzeneacetic acid (0.5 g, 1.98 mmole) and potassium thiocyanate (0.4 g, 4.12 mmole) in 10 ml of methanol is stirred at room temperature for 16 hours. The reaction mixture is filtered to remove the potassium chloride, the filtrate is evaporated and to the residue is added saturated aqueous sodium bicarbonate until the pH is 7. The title compound precipitates as a white powder which is filtered and dried. (1.83 g, 78% yield), NMR (TFA-D+D2O) ppm (δ) 4.1 (s,2), 5.08 (s,1), 6.9-7.3 (m,3). | N#CSCc1cc(C(N)C(=O)O)ccc1O | null | 78 | null |
134,441 | ord_dataset-b76b52f4448a4eedb28ffcd8f902046a | null | 1985-01-01T00:09:00 | true | [CH3:1][O:2][C:3](=[O:28])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[C:9]([C:25](=[O:27])[CH3:26])[C:10]([O:16][CH2:17][CH2:18][CH2:19][O:20][CH2:21][CH2:22][CH2:23]Br)=[CH:11][CH:12]=2)[CH:7]=1.[OH:29][C:30]1[C:35]([CH2:36][CH2:37][CH3:38])=[C:34]([OH:39])[CH:33]=[CH:32][C:31]=1[C:40](=[O:42])[CH3:41].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O.CN(C)C=O>[CH3:1][O:2][C:3](=[O:28])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[C:9]([C:25](=[O:27])[CH3:26])[C:10]([O:16][CH2:17][CH2:18][CH2:19][O:20][CH2:21][CH2:22][CH2:23][O:39][C:34]3[CH:33]=[CH:32][C:31]([C:40](=[O:42])[CH3:41])=[C:30]([OH:29])[C:35]=3[CH2:36][CH2:37][CH3:38])=[CH:11][CH:12]=2)[CH:7]=1 | COC(=O)COc1ccc2ccc(OCCCOCCCBr)c(C(C)=O)c2c1 | CCCc1c(O)ccc(C(C)=O)c1O | 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 | CC(C)=O | null | null | null | null | null | null | null | null | null | null | null | A mixture of 1.73 g of [[8-acetyl-7-[3-(3-bromopropoxy)propoxy]-2-naphthalenyl]oxy]acetic acid methyl ester, 0.89 g of 1-(2,4-dihydroxy-3-propylphenyl)ethanone and 0.79 g of anhydrous potassium carbonate in 33 ml of anhydrous acetone and 11 ml of anhydrous dimethylformamide was stirred at reflux for 18 hours. The mixture was filtered and filtrate was concentrated in vacuo to an oil. Purification by high pressure liquid chromatography (10% ethyl acetate-toluene) gave 1.2 g (56%) of [[8-acetyl-7-[3-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propoxy]propoxy]-2-naphthalenyl]oxy]acetic acid methyl ester. | CCCc1c(OCCCOCCCOc2ccc3ccc(OCC(=O)OC)cc3c2C(C)=O)ccc(C(C)=O)c1O | null | 55.5 | null |
316,454 | ord_dataset-fd1553bae35046c7a67523ff472cb5c3 | null | 1995-01-01T00:09:00 | true | [CH3:1][O:2][N:3]=[C:4]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[C:15]#[CH:16])[C:5](OC)=[O:6].[CH3:17][NH2:18]>>[CH3:1][O:2][N:3]=[C:4]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[C:15]#[CH:16])[C:5]([NH:18][CH3:17])=[O:6] | C#Cc1ccccc1C(=NOC)C(=O)OC | CN | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | 0.75 | 1 g (4.6 mmol) of the acetylene compound prepared in Example 1 is added to 20 ml of a 40% strength methylamine solution, and the mixture is stirred for 45 minutes at 40°-50° C. The solution is extracted with methyl tert-butyl ether, dried and evaporated down. 700 mg (70%) of the compound remain as a colorless solid. | C#Cc1ccccc1C(=NOC)C(=O)NC | null | null | null |
1,519,072 | ord_dataset-8c74302143c04eb9983e4b3a7ead2d72 | null | 2014-01-01T00:12:00 | true | [CH3:1][C:2]1([CH3:25])[CH2:11][CH2:10][C:9]([CH3:13])([CH3:12])[C:8]2[CH:7]=[C:6]([C:14]3[N:18]=[C:17]([N:19]4[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]4)[S:16][N:15]=3)[CH:5]=[CH:4][C:3]1=2.C([O:29][CH2:30][CH2:31][CH2:32][CH2:33]Br)(=O)C.[OH-].[Na+]>CO>[CH3:1][C:2]1([CH3:25])[CH2:11][CH2:10][C:9]([CH3:12])([CH3:13])[C:8]2[CH:7]=[C:6]([C:14]3[N:18]=[C:17]([N:19]4[CH2:20][CH2:21][N:22]([CH2:33][CH2:32][CH2:31][CH2:30][OH:29])[CH2:23][CH2:24]4)[S:16][N:15]=3)[CH:5]=[CH:4][C:3]1=2 | CC1(C)CCC(C)(C)c2cc(-c3nsc(N4CCNCC4)n3)ccc21 | CC(=O)OCCCCBr | null | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | null | null | The preparation was carried out as already described starting from 65 mg (0.16 mmol) of 1-[3-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-1,2,4-thiadiazol-5-yl]piperazine and 36 μl (0.25 mmol) of 4-bromobutyl acetate. The protecting group was cleaved off by means of a 1N NaOH solution in methanol. The product was purified by means of preparative HPLC and is in the form of the hydrochloride. | CC1(C)CCC(C)(C)c2cc(-c3nsc(N4CCN(CCCCO)CC4)n3)ccc21 | null | null | null |
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