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 ⌀ |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
68,585 | ord_dataset-dabcd66611f34094b1baca0095305a66 | null | 1980-01-01T00:07:00 | true | B#B.[CH3:3][S:4]([O:7][CH2:8][CH2:9][CH2:10][C:11]1([CH3:21])[CH:17]2[O:18][C:14]([CH:19]=[CH2:20])([CH2:15][CH2:16]2)[CH2:13][O:12]1)(=[O:6])=[O:5].[OH-:22].[Na+].OO>O1CCCC1.O>[CH3:3][S:4]([O:7][CH2:8][CH2:9][CH2:10][C:11]1([CH3:21])[CH:17]2[O:18][C:14]([CH2:19][CH2:20][OH:22])([CH2:15][CH2:16]2)[CH2:13][O:12]1)(=[O:5])=[O:6] | [OH-] | C=CC12CCC(O1)C(C)(CCCOS(C)(=O)=O)OC2 | null | B#B | OO | [Na+] | 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 | null | A mixture of diborane in tetrahydrofuran (1 ml, 1 mM) is added slowly to a mixture of (1RS,4SR,5RS)-4-(3-methanesulfonyloxypropyl)-4-methyl-1-vinyl-3,8-dioxabicyclo[3.2.1]octane (350 mg, 1.2 mM) and tetrahydrofuran (5 ml) at 0° C. under nitrogen and stirred for thirty minutes. The resulting mixture is allowed to warm to room temperature and stirred for an additional two hours. The mixture is cooled to 0° C. and 3 N sodium hydroxide (0.3 ml) is added followed by the addition of 30% hydrogen peroxide (0.3 ml). The resulting mixture is allowed to warm to room temperature and stirred for 2.5 hours. The mixture is then treated with water (10 ml) and extracted with ether (5×20 ml). The combined organic phases are dried (Na2SO4) and the solvent is removed in vacuo. The residue is purified by column chromatography on silica gel (30 g) with ether to give (1RS,4SR,5RS)-4-(3-methanesulfonyloxypropyl)-4-methyl-3,8-dioxabicyclo[3.2.1]octane-1-ethanol (275 mg, 80%) as a colorless oil. | CC1(CCCOS(C)(=O)=O)OCC2(CCO)CCC1O2 | null | 80 | null |
96,346 | ord_dataset-be22f1f5114b4ebfb8d447c93d62d62c | null | 1982-01-01T00:07:00 | true | [C:1]([O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([N+:12]([O-])=O)[C:7]=1[Br:15])(=[O:3])[CH3:2].N1CCOCC1>CO.[Pt]=O>[C:1]([O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([NH2:12])[C:7]=1[Br:15])(=[O:3])[CH3:2] | CC(=O)OCc1cccc([N+](=O)[O-])c1Br | null | null | O=[Pt] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1COCCN1 | CO | null | null | null | null | null | null | null | null | null | null | null | A mixture of 5.7 grams (0.022 mole) of 2-bromo-3-nitrophenylmethyl acetate, 0.1 gram of platinum oxide and 2.0 ml of morpholine in 200 ml of methanol was hydrogenated using a Parr hydrogenator. The hydrogenation required 2.25 hours. The reaction mixture was filtered and the filtrate concentrated under reduced pressure to give 6.2 grams of 3-amino-2-bromophenylmethyl acetate. | CC(=O)OCc1cccc(N)c1Br | null | 115.5 | null |
463,987 | ord_dataset-6c36eb0f817d4144988b8963c5d58879 | null | 2000-01-01T00:05:00 | true | [Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[C:6]([CH:9]=1)[CH:7]=O.[NH2:18][C:19]1[CH:28]=[CH:27][C:22]([C:23]([O:25][CH3:26])=[O:24])=[CH:21][CH:20]=1>C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[C:6]([CH:9]=1)[CH2:7][NH:18][C:19]1[CH:20]=[CH:21][C:22]([C:23]([O:25][CH3:26])=[O:24])=[CH:27][CH:28]=1 | O=Cc1cc(Br)ccc1CCc1ccccc1 | COC(=O)c1ccc(N)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Cc1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | 18 | 5-Bromo-2-(phenethyl)benzaldehyde (1.27 g) and methyl 4-aminobenzoate (0.66 g) were heated together at 110° C. for 30 minutes and for a further 30 minutes under vacuum. The mixture was dissolved in toluene, evaporated to dryness, dissolved in ethanol (15 ml). Sodium borohydride (0.33 g) was added, the mixture stirred for 18 hours, the solvent evaporated and the residue mixed with acetic acid and partitioned between saturated aqueous sodium hydrogen carbonate and ethyl acetate. The organic layer was washed with brine, dried (MgSO4), filtered and evaporated. The resulting residue was purified by MPLC, eluting with dichloromethane, to give methyl 4-[N-(5-bromo-2-(phenethyl)benzyl)amino]benzoate (1.65 g). | COC(=O)c1ccc(NCc2cc(Br)ccc2CCc2ccccc2)cc1 | null | 89.1 | null |
411,978 | ord_dataset-fbdd058349aa456f812e3546c84baab5 | null | 1998-01-01T00:09:00 | true | [CH2:1]([C:3]1[C:4](=[O:29])[N:5]([C:9]([NH:11][CH2:12][CH:13]2[C:22]3[C:17](=[CH:18][C:19]([O:27][CH3:28])=[C:20]([S:23](=[O:26])(=[O:25])[NH2:24])[CH:21]=3)[O:16][CH2:15][CH2:14]2)=[O:10])[CH2:6][C:7]=1[CH3:8])[CH3:2].[CH:30]([N:33]=[C:34]=[S:35])([CH3:32])[CH3:31]>>[CH2:1]([C:3]1[C:4](=[O:29])[N:5]([C:9]([NH:11][CH2:12][CH:13]2[C:22]3[C:17](=[CH:18][C:19]([O:27][CH3:28])=[C:20]([S:23]([NH:24][C:34]([NH:33][CH:30]([CH3:32])[CH3:31])=[S:35])(=[O:25])=[O:26])[CH:21]=3)[O:16][CH2:15][CH2:14]2)=[O:10])[CH2:6][C:7]=1[CH3:8])[CH3:2] | CC(C)N=C=S | CCC1=C(C)CN(C(=O)NCC2CCOc3cc(OC)c(S(N)(=O)=O)cc32)C1=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 | 4-((3-Ethyl-4-methyl-2-oxo-3-pyrroline-1-carboxamido) methyl)-6-(isopropylaminothiocarbonylaminosulfonyl)-7-methoxychroman ##STR50## 4-((3-Ethyl-4-methyl-2-oxo-3-pyrroline-1-carboxamido) methyl)-6-(isopropylaminothiocarbonylaminosulfonyl)-7-methoxychroman is synthesized following Example 14 starting from 4-((3-ethyl-4-methyl-2-oxo-3-pyrroline-1-carboxamido)methyl)6-sulfamoyl-7-methoxychroman and isopropyl isothiocyanate. Melting point: 153° C. | CCC1=C(C)CN(C(=O)NCC2CCOc3cc(OC)c(S(=O)(=O)NC(=S)NC(C)C)cc32)C1=O | null | null | null |
1,224,535 | ord_dataset-cde802cdb7434a5f82a22981ccaefc4e | null | 2012-01-01T00:11:00 | true | [OH:1][C@H:2]([CH:6]([CH3:8])[CH3:7])[C:3]([OH:5])=[O:4].[CH3:9]O>CCCCCC>[OH:1][C@H:2]([CH:6]([CH3:8])[CH3:7])[C:3]([O:5][CH3:9])=[O:4] | CC(C)[C@@H](O)C(=O)O | CO | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCCCCC | null | null | null | null | null | null | null | null | null | null | 0 | 1 | To a solution of (R)-2-hydroxy-3-methylbutanoic acid (5.0 gm, 42.2 mmol) in methanol was added a solution of TMS.CH2N2 (2M) in hexane (65 mL), at 0° C., over 20 min. The reaction mixture was stirred at 0° C. for 1 h. The reaction was concentrated with a bath temperature of 20° C. and vacuum greater than 50 mm Hg. Purification via silica gel chromatography using 2-100% EtOAc in hexanes gave the ester as a yellow oil (438 mg, 12.7 mmol, 30% yield). 1H NMR (400 MHz, DMSO-d6) δ 5.30 (d, J=5.1 Hz, 1H), 3.81 (t, J=0.8 Hz, 1H), 3.63 (s, 3H), 1.94-1.86 (m, 1H), 0.88-0.82 (m, 6H). | COC(=O)[C@H](O)C(C)C | null | 30 | null |
1,614,157 | ord_dataset-35c51552812941cda45194a013d34bb9 | null | 2015-01-01T00:08:00 | true | Cl.[CH3:2][S:3][CH2:4][CH2:5][CH:6]1[NH:11][C:10](=[O:12])[CH:9]([CH2:13][CH2:14][S:15][CH3:16])[NH:8][C:7]1=[O:17].[OH2:18]>>[NH2:8][C@H:9]([C:10]([NH:11][C@H:6]([C:7]([OH:17])=[O:18])[CH2:5][CH2:4][S:3][CH3:2])=[O:12])[CH2:13][CH2:14][S:15][CH3:16] | O | CSCCC1NC(=O)C(CCSC)NC1=O | 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 | 110 | 2 | 500 l of water were introduced into a 500 l enameled tank with stirrer, 32 l of concentrated hydrochloric acid and 78.6 kg of 3,6-bis[2-(methylthio)ethyl]-2,5-piperazinedione (III) (DKP) were added, and the apparatus was closed tightly. It was then heated at 110° C. while stirring for 2 hours, during which the pressure rose to 2.5 bar and the DKP (III) virtually completely dissolved. After the reaction was complete, the mixture was cooled to 20° C., and the unreacted DKP was spun down in a centrifuge. The solid was washed with 10 l of water. The filtrate and washing water were then collected in an 800 l container and subsequently introduced into a 500 l tank with stirrer again. Addition of 2 kg of activated carbon was followed by stirring at 20° C. for 30 min. The suspension was then filtered through a filter press into a further 500 l tank with stirrer. About 28 l of concentrated ammonia solution were then added to precipitate at pH 6 the DD/LL/DL/LD-methionylmethionine (I). During this there was an initial preferential precipitation of the less soluble racemic pair of diastereomers DL/LD-methionylmethionine (DL/LD-I). This was spun down and the mother liquor was concentrated together with washing water to one quarter of the original volume in vapor pump vacuum at an internal temperature not exceeding 40° C. During this, the more soluble racemic pair of diastereomers DD/LL-methionylmethionine (DD/LL-I) crystallized together with small amounts of the slightly soluble DL/LD-I. Completion of the distillation was followed by cooling to 20° C. and centrifugation. The separated mother liquor and washing water were discarded. Both fractions were dried in vacuo at 70° C. In total, it was possible to obtain 64.2 kg (78%) of DD/LL/DL/LD-methionyl-methionine (I) as mixture of diastereomers. Purity >98% (HPLC). | CSCC[C@H](NC(=O)[C@@H](N)CCSC)C(=O)O | null | null | null |
541,966 | ord_dataset-49124ff635234889bd8dcfe87f4f9013 | null | 2002-01-01T00:04:00 | true | [CH2:1]1[CH2:12][O:11][C:10]2[C:3](=[C:4]([CH:7]=[CH:8][CH:9]=2)[CH:5]=[O:6])[O:2]1.[Mn]([O-])(=O)(=O)=[O:14].[K+].[OH-].[K+]>O>[CH2:1]1[CH2:12][O:11][C:10]2[C:3](=[C:4]([CH:7]=[CH:8][CH:9]=2)[C:5]([OH:14])=[O:6])[O:2]1 | O=Cc1cccc2c1OCCO2 | O=[Mn](=O)(=O)[O-] | null | [K+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | null | null | null | null | null | null | null | null | null | null | null | 1.5 | Into a 500 ml round bottom flask fitted with a 250 ml addition funnel and a magnetic stir bar were placed 2,3-ethylenedioxybenzaldehyde (4.07 g, 24.7 mmol) and 100 ml of water. The mixture was heated to 80° and potassium permanganate (7.84 g, 49.6 mmol) in 150 ml of water was added dropwise via the addition funnel over 20 minutes. After the addition was complete the mixture was allowed to stir at 80° for 1.5 hours. The mixture was made basic with a 10% potassium hydroxide solution and the solids filtered. The filter cake was washed with hot water. The filtrate was extracted with ether, made acidic, then extracted with ethyl acetate. The organics were dried over sodium sulfate, filtered, and concentrated to give 2.96 g of subtitled product (66%) which was used directly in the next step. | O=C(O)c1cccc2c1OCCO2 | null | 66.5 | null |
444,208 | ord_dataset-ba7561dae3884c07a8beddd0b9f1222e | null | 1999-01-01T00:10:00 | true | C([Li])CCC.Br[C:7]1[CH:12]=[C:11]([CH3:13])[C:10]([N:14]2[C:18]([CH2:19][CH3:20])=[C:17]([CH2:21][N:22]3[C@@H:31]([CH2:32][O:33][CH2:34][CH3:35])[CH2:30][C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[CH2:23]3)[C:16]([CH2:36][CH3:37])=[N:15]2)=[C:9]([CH3:38])[CH:8]=1.[CH3:39][C:40]([CH3:42])=[O:41]>O1CCCC1>[CH2:34]([O:33][CH2:32][C@H:31]1[CH2:30][C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH2:23][N:22]1[CH2:21][C:17]1[C:16]([CH2:36][CH3:37])=[N:15][N:14]([C:10]2[C:11]([CH3:13])=[CH:12][C:7]([C:40]([OH:41])([CH3:42])[CH3:39])=[CH:8][C:9]=2[CH3:38])[C:18]=1[CH2:19][CH3:20])[CH3:35] | CC(C)=O | CCOC[C@H]1Cc2ccccc2CN1Cc1c(CC)nn(-c2c(C)cc(Br)cc2C)c1CC | null | [Li]CCCC | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | -78 | 0.17 | To a solution of n-butyl lithium (2.5 M hexane solution; 0.16 ml, 0.39 mmol) chilled to -78° C., a solution of (R)-2-[1-(4-bromo-2,6-dimethylphenyl)-3,5-diethyl-1H-pyrazol-4-ylmethyl]-3-ethoxymethyl-1,2,3,4-tetrahydro-isoquinoline (180 mg, 0.35 mmol) in anhydrous tetrahydrofuran (1.0 ml) was added dropwise. After stirring at -78° C. for 10 minutes, anhydrous acetone (0.078 ml, 1.1 mmol) was added. The resulting mixture was warmed to ambient temperature, and stirred at that temperature for 1 hour. The reaction was quenched by addition of aqueous ammonium chloride (2 ml) and then extracted with ethyl acetate/water (5 ml of each). The separated organic extract was then extracted with an equal volume solution of aqueous ammonium chloride. The combined aqueous extracts were then extracted with a fresh equal-volume portion of ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate, and concentrated in vacuo to afford a yellow oil. Flash chromatography of the entire sample (silica gel, 40 micron mesh; elution with ethyl acetate/hexane=1:2 in volume) afforded the title compound (120 mg) as a faint yellow oil. | CCOC[C@H]1Cc2ccccc2CN1Cc1c(CC)nn(-c2c(C)cc(C(C)(C)O)cc2C)c1CC | null | 70 | null |
1,168,640 | ord_dataset-d24cc23b3db94284bb83a2ccdd9eb880 | null | 2012-01-01T00:05:00 | true | C(NCC)C.Br[CH2:7][C:8]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:9].[C:16](#[N:20])[CH2:17][C:18]#[N:19]>CN(C=O)C>[NH2:20][C:16]1[O:9][C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:7][C:17]=1[C:18]#[N:19] | O=C(CBr)c1ccccc1 | N#CCC#N | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | CCNCC | null | null | null | null | null | null | null | null | null | 25 | 1 | Add 68.6 ml (663 mmol) diethylamine dropwise to a mixture of 60.0 g (301 mmol) bromoacetophenone and 25.89 g (391.86 mmol) malononitrile in 130 ml DMF at RT (cooling is required to maintain the temperature). Towards the end of addition, remove the cooling, stir the mixture for 1 h at RT and then add water to 385 ml. Dilute with a further 125 ml water and stir for 20 min at RT. Filter off the precipitated solids with suction, wash twice with 125 ml water each time, dry under suction and wash with petroleum ether. Dry the residue at high vacuum. 33.3 g (50.1% of theor.) of the target compound is obtained as yellowish-brown crystals. | N#Cc1cc(-c2ccccc2)oc1N | null | null | null |
658,920 | ord_dataset-be508e976bbb4586a0cc3368302a62f8 | null | 2005-01-01T00:01:00 | true | [OH:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][NH:7][C:8]2=[O:11])=[CH:4][CH:3]=1.[F:12][C:13]1[CH:14]=[C:15]([CH:18]=[CH:19][CH:20]=1)[CH2:16]Br.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[F:12][C:13]1[CH:14]=[C:15]([CH:18]=[CH:19][CH:20]=1)[CH2:16][O:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][NH:7][C:8]2=[O:11])=[CH:4][CH:3]=1 | O=C1NCc2ccc(O)cc21 | Fc1cccc(CBr)c1 | null | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(C)=O | null | null | null | null | null | null | null | null | null | null | 25 | null | A mixture of 6-hydroxy-2,3-dihydro-isoindol-1-one (125.0 mg, 0.84 mmol) and 3-fluorobenzylbromide (174.3 mg, 0.92 mmol) in acetone (5 mL) containing potassium carbonate (276.4 mg, 2.0 mmol) was heated under reflux for 17 h. After cooling to RT the mixture was filtered and evaporated. The residue was purified by chromatography (SiO2, CH2Cl2:2N NH3-MeOH 90:10) to afford the title product (180 mg, 83%) as a white solid. MS m/e=258.2 (M+H+). | O=C1NCc2ccc(OCc3cccc(F)c3)cc21 | null | 83.3 | null |
1,443,515 | ord_dataset-275a3da8f45f4536ad29727f0ef9ba66 | null | 2014-01-01T00:06:00 | true | [CH2:1]([N:3]1[CH2:8][CH2:7][CH:6]([C:9]2[CH:14]=[CH:13][C:12]([N+:15]([O-])=O)=[CH:11][CH:10]=2)[CH2:5][CH2:4]1)[CH3:2]>[Pd].CCO>[CH2:1]([N:3]1[CH2:8][CH2:7][CH:6]([C:9]2[CH:10]=[CH:11][C:12]([NH2:15])=[CH:13][CH:14]=2)[CH2:5][CH2:4]1)[CH3:2] | CCN1CCC(c2ccc([N+](=O)[O-])cc2)CC1 | null | null | [Pd] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | null | null | null | null | null | null | null | null | null | null | 25 | 3 | A suspension of 1-ethyl-4-(4-nitro-phenyl)-piperidine (0.8 g, 4.92 mmol) and 10% palladium on carbon (0.1 g) in EtOH (10 mL) is stirred for 3 h at RT, under a hydrogen atmosphere. The reaction mixture is filtered through a pad of celite and concentrated. The residue is purified by silica gel column chromatography (DCM/MeOH+1% NH3aq, 95:5) to provide the title compound. ESI-MS: 205.1 [MH]+; TLC: Rf=0.29 (DCM/MeOH+1% NH3aq, 95:5). | CCN1CCC(c2ccc(N)cc2)CC1 | null | null | null |
1,373,826 | ord_dataset-d23f2f15886d4c22b7d7ba5f0e203e81 | null | 2013-01-01T00:12:00 | true | [Cl:1][C:2]1[CH:39]=[CH:38][C:5]2[N:6]([CH3:37])[C:7](=[O:36])[CH:8]([CH2:25][C:26]3[CH:35]=[CH:34][C:33]4[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=4)[CH:27]=3)[N:9]=[C:10]([N:11]3[CH2:16][CH2:15][CH:14]([NH:17]C(=O)OC(C)(C)C)[CH2:13][CH2:12]3)[C:4]=2[CH:3]=1.FC(F)(F)C(O)=O>ClCCl>[NH2:17][CH:14]1[CH2:13][CH2:12][N:11]([C:10]2[C:4]3[CH:3]=[C:2]([Cl:1])[CH:39]=[CH:38][C:5]=3[N:6]([CH3:37])[C:7](=[O:36])[CH:8]([CH2:25][C:26]3[CH:35]=[CH:34][C:33]4[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=4)[CH:27]=3)[N:9]=2)[CH2:16][CH2:15]1 | CN1C(=O)C(Cc2ccc3ccccc3c2)N=C(N2CCC(NC(=O)OC(C)(C)C)CC2)c2cc(Cl)ccc21 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | O=C(O)C(F)(F)F | null | null | null | null | null | null | null | null | null | null | null | 5,7-Dichloro-1-methyl-3-(naphthalen-2-ylmethyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (170 mg, 0.44 mmol) and tert-butyl piperidin-4-ylcarbamate (89 mg, 0.44 mmol) were coupled according to the corresponding procedure described in Example 14 to yield intermediate tert-butyl 1-(7-chloro-1-methyl-3-(naphthalen-2-ylmethyl)-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-5-yl)piperidin-4-ylcarbamate. (85 mg, 35%). Tert-butyl 1-(7-chloro-1-methyl-3-(naphthalen-2-ylmethyl)-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-5-yl)piperidin-4-ylcarbamate (85 mg, 0.16 mmol) was dissolved in dichloromethane (1 mL) and trifluoroacetic acid (1 mL) and stirred at ambient temperature for 2 hours. The solution was concentrated, redissolved in ethyl acetate and extracted into 1 M aqueous hydrochloric acid (3×10 mL). The extracts were neutralized with saturated sodium bicarbonate, extracted with dichloromethane (3×25 mL), then dried with sodium sulfate, filtered, and concentrated to yield 5-(4-aminopiperidin-1-yl)-7-chloro-1-methyl-3-(naphthalen-2-ylmethyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (20 mg, 29% yield). MS (M+H)+447.2. | CN1C(=O)C(Cc2ccc3ccccc3c2)N=C(N2CCC(N)CC2)c2cc(Cl)ccc21 | null | 28 | null |
1,516,719 | ord_dataset-8c74302143c04eb9983e4b3a7ead2d72 | null | 2014-01-01T00:12:00 | true | [F:1][C:2]1[CH:14]=[C:13]([N+:15]([O-])=O)[CH:12]=[CH:11][C:3]=1[C:4]([NH:6][CH2:7][C:8]([OH:10])=[O:9])=[O:5].C([O-])=O.[NH4+]>CO.[Zn]>[NH2:15][C:13]1[CH:12]=[CH:11][C:3]([C:4]([NH:6][CH2:7][C:8]([OH:10])=[O:9])=[O:5])=[C:2]([F:1])[CH:14]=1 | O=C(O)CNC(=O)c1ccc([N+](=O)[O-])cc1F | null | null | O=C[O-] | [NH4+] | [Zn] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | 25 | 0.25 | To a solution of 2-(2-fluoro-4-nitrobenzamido)acetic acid (100 mg, 0.413 mmol) in methanol (15 mL) was added successively zinc dust (270 mg, 4.132 mmol) and ammonium formate (260 mg, 4.132 mmol) at rt. The reaction mixture was stirred at rt for 15 min. The reaction mixture was filtered and washed with methanol (2×5 mL). The residue obtained after evaporation of the solvents was diluted with water (5 mL) and acidified with AcOH (3 mL). The solution was extracted with EtOAc (3×50 mL) and the combined organic layer was dried over anhyd Na2SO4. The solution was filtered and evaporated the solvent. The residue was chromatographed over silica gel column using chloroform:methanol (70:30) as eluents to give the product as a white color solid (59 mg, 67%), mp 190-194° C. | Nc1ccc(C(=O)NCC(=O)O)c(F)c1 | null | 67.3 | null |
814,073 | ord_dataset-892acf7477db4d3a8a8559f004a7c0a2 | null | 2008-01-01T00:03:00 | true | C[O:2][C:3](=[O:31])[C@@H:4]([O:28][CH2:29][CH3:30])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][C:14]2[N:15]=[C:16]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[F:26])[O:17][C:18]=2[CH3:19])=[CH:8][C:7]=1[F:27].[Li+].[OH-]>>[CH2:29]([O:28][C@@H:4]([CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][C:14]2[N:15]=[C:16]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[F:26])[O:17][C:18]=2[CH3:19])=[CH:8][C:7]=1[F:27])[C:3]([OH:31])=[O:2])[CH3:30] | CCO[C@@H](Cc1ccc(OCc2nc(-c3ccccc3F)oc2C)cc1F)C(=O)OC | null | null | [Li+] | [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 | null | In analogy to the procedure described in example 1 g], (S)-2-ethoxy-3-{2-fluoro-4-[2-(2-fluoro-phenyl)-5-methyl-oxazol-4-ylmethoxy]-phenyl}-propionic acid methyl ester was treated with LiOH to obtain (S)-2-ethoxy-3-{2-fluoro-4-[2-(2-fluoro-phenyl)-5-methyl-oxazol-4-ylmethoxy]-phenyl}-propionic acid as colorless liquid. | CCO[C@@H](Cc1ccc(OCc2nc(-c3ccccc3F)oc2C)cc1F)C(=O)O | null | null | null |
1,480,106 | ord_dataset-c3c1091f873b4f40827973a6f1f9b685 | null | 2014-01-01T00:09:00 | true | [OH-].[Na+].Cl.[N+:4]([C:7]1[CH:8]=[C:9]([NH:13][NH2:14])[CH:10]=[CH:11][CH:12]=1)([O-:6])=[O:5].C(O)(=O)C.[CH:19](=O)[CH2:20][CH3:21]>C(O)C>[N+:4]([C:7]1[CH:8]=[C:9]([NH:13][N:14]=[CH:19][CH2:20][CH3:21])[CH:10]=[CH:11][CH:12]=1)([O-:6])=[O:5] | CCC=O | NNc1cccc([N+](=O)[O-])c1 | null | Cl | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(=O)O | CCO | null | null | null | null | null | null | null | null | null | 25 | 3 | Sodium hydroxide solution (10%, 15 mL) was added slowly to a stirred suspension of (3-nitro-phenyl)-hydrazine hydrochloride salt (B-4-a) (1.89 g, 10 mmol) in ethanol (20 mL) until pH 6. Acetic acid (5 mL) was added to the mixture followed by propionaldehyde (0.7 g, 12 mmol). After stirring for 3 h at room temperature, the mixture was poured into ice-water and the resulting precipitate was isolated via filtration, washed with water and dried in air to obtain N-(3-nitro-phenyl)-N′-propylidene-hydrazine, which was used directly in the next step. | CCC=NNc1cccc([N+](=O)[O-])c1 | null | null | null |
1,326,805 | ord_dataset-cfad8b3f00044bcda60a96b019f09872 | null | 2013-01-01T00:08:00 | true | O1CCCC1.[NH2:6][C:7]1[C:12]([C:13]2[O:17][N:16]=[C:15]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([OH:25])=[CH:21][CH:20]=3)[CH:14]=2)=[CH:11][CH:10]=[C:9]([NH2:26])[N:8]=1.[OH-].[Na+].Cl[CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([F:37])[N:32]=1>CN(C)C=O>[F:37][C:33]1[N:32]=[C:31]([CH2:30][O:25][C:22]2[CH:23]=[CH:24][C:19]([CH2:18][C:15]3[CH:14]=[C:13]([C:12]4[C:7]([NH2:6])=[N:8][C:9]([NH2:26])=[CH:10][CH:11]=4)[O:17][N:16]=3)=[CH:20][CH:21]=2)[CH:36]=[CH:35][CH:34]=1 | Fc1cccc(CCl)n1 | Nc1ccc(-c2cc(Cc3ccc(O)cc3)no2)c(N)n1 | null | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | CN(C)C=O | null | null | null | null | null | null | null | null | null | 25 | 14 | To a tetrahydrofuran (3 mL) solution of 4-(5-(2,6-diamino-pyridin-3-yl)-isoxazol-3-ylmethyl)-phenol (40 mg, 0.14 mmol) described in Manufacturing Example 18-1-1 was added a 5 N sodium hydroxide aqueous solution (28.3 μL, 0.14 mmol), which was dissolved by irradiating ultrasonic wave for 1 minute. The reaction solution was concentrated under a reduced pressure, which gave a white solid. To a suspension of this solid in N,N-dimethylformamide (1 mL) was added an N,N-dimethylformamide (1 mL) solution of 2-chloromethyl-6-fluoro-pyridine (52.7 mg, 0.36 mmol) described in manufacturing Example 45-1-1, which was stirred for 14 hours at room temperature. The reaction mixture was partitioned into water and ethyl acetate. The organic layer was separated, washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure. The residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=1:2), and then further purified by reverse-phase high performance liquid chromatography (using an acetonitrile-water mobile phase containing 0.1% trifluoroacetic acid) to obtain the title compound (7.8 mg, 11%) as a trifluoroacetic acid salt. | Nc1ccc(-c2cc(Cc3ccc(OCc4cccc(F)n4)cc3)no2)c(N)n1 | null | 14.2 | null |
1,446,310 | ord_dataset-a86112d52cd54525a5e36d41f18aced2 | null | 2014-01-01T00:07:00 | true | [CH3:1][N:2]1[C:6]2=[N:7][C:8]([C:11]3[CH:18]=[CH:17][CH:16]=[CH:15][C:12]=3[C:13]#[N:14])=[CH:9][CH:10]=[C:5]2[NH:4][C:3]1=[O:19].C(=O)([O-])[O-].[Cs+].[Cs+].[F:26][C:27]1[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:31][C:28]=1[CH2:29]Br>CN1C(=O)CCC1.CO>[F:26][C:27]1[CH:34]=[CH:33][C:32]([C:35]([F:36])([F:37])[F:38])=[CH:31][C:28]=1[CH2:29][N:4]1[C:5]2[C:6](=[N:7][C:8]([C:11]3[CH:18]=[CH:17][CH:16]=[CH:15][C:12]=3[C:13]#[N:14])=[CH:9][CH:10]=2)[N:2]([CH3:1])[C:3]1=[O:19] | Cn1c(=O)[nH]c2ccc(-c3ccccc3C#N)nc21 | Fc1ccc(C(F)(F)F)cc1CBr | null | O=C([O-])[O-] | [Cs+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | CN1CCCC1=O | null | null | null | null | null | null | null | null | null | 90 | null | 2-(3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-5-yl)benzonitrile (4-1) (30 mg, 0.12 mmol) and cesium carbonate (117 mg, 0.36 mmol) were added to a microwave vial and suspended in NMP (0.5 mL) under nitrogen. 2-Fluoro-5-(trifluoromethyl)benzyl bromide (47 mg, 0.18 mmol) was added to the suspension and then heated at 90° C. overnight. The mixture was diluted with methanol and purified using reverse phase chromatography (10-100%, 0.1% TFA in H2O/Acetonitrile); the desired fractions were collected and concentrated to produce 2-{1-[2-fluoro-5-(trifluoromethyl)benzyl]-3-methyl-2-oxo-2,3-dihydro 1H-imidazo[4,5-b]pyridin-5-yl}benzonitrile (6-1). HRMS (M+H)+: observed=427.1179, calculated=427.1177. | Cn1c(=O)n(Cc2cc(C(F)(F)F)ccc2F)c2ccc(-c3ccccc3C#N)nc21 | null | null | null |
709,369 | ord_dataset-c8069773c1a148aca8ab417108daacc5 | null | 2006-01-01T00:05:00 | true | [CH3:1][N:2]([CH3:7])[CH2:3][CH2:4][CH2:5][OH:6].O[C:9]1[CH:19]=[CH:18][C:12]2[NH:13][C:14](=[O:17])[CH2:15][S:16][C:11]=2[CH:10]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[CH3:1][N:2]([CH3:7])[CH2:3][CH2:4][CH2:5][O:6][C:9]1[CH:19]=[CH:18][C:12]2[NH:13][C:14](=[O:17])[CH2:15][S:16][C:11]=2[CH:10]=1 | CN(C)CCCO | O=C1CSc2cc(O)ccc2N1 | null | CCOC(=O)N=NC(=O)OCC | c1ccc(P(c2ccccc2)c2ccccc2)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | 25 | 48 | N,N-dimethyl-3-aminopropanol (0.27 g, 5.2 mmol) was added to a mixture of 7-hydroxy-2H-1,4-benzothiazin-3(4H)-one (0.95 g, 5.2 mmol) and triphenylphosphine (1.37 g, 5.2 mmol) in dry tetrahydrofurane (30 ml) under nitrogen atmosphere, followed by diethyl azodicarboxylate (1 g, 5.7 mmol). The mixture was stirred at room temperature for 48 h, concentrated in vacuo, and the product was purified by silica gel chromatography using dichloromethane:methanol gradient of (9:1) to (7:3) as the mobile phase. Yield 1.1 g (75%) mp 120–121° C. | CN(C)CCCOc1ccc2c(c1)SCC(=O)N2 | null | null | null |
1,742,287 | ord_dataset-60a3e71da3174666a50a61dcfa611a9f | null | 2016-01-01T00:07:00 | true | [CH:1]1([NH:4][C:5]2[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:6]=2[NH:12][C:13]([C:15]2[CH:16]=[N:17][CH:18]=[C:19]([F:21])[CH:20]=2)=O)[CH2:3][CH2:2]1>C(O)(=O)C>[CH:1]1([N:4]2[C:5]3[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:6]=3[N:12]=[C:13]2[C:15]2[CH:16]=[N:17][CH:18]=[C:19]([F:21])[CH:20]=2)[CH2:3][CH2:2]1 | O=C(Nc1ccc(F)cc1NC1CC1)c1cncc(F)c1 | null | 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 | 25 | null | A solution of the title compound from Step A (0.038 g, 0.131 mmol) in acetic acid (0.66 mL) was heated at 100° C. for 1 hour, then cooled to room temperature and concentrated under reduced pressure. The resulting residue was diluted with ethyl acetate, washed sequentially with aqueous 1 N sodium hydroxide solution and brine, dried over magnesium sulfate, filtered and concentrated. Purification by flash chromatography (30-50% ethyl acetate in hexanes) provided the title compound: LCMS m/z 272.16 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 9.06 (s, 1 H), 8.60 (d, J=2.7 Hz, 1 H), 8.03 (m, 1 H), 7.73 (dd, J=8.8, 4.8 Hz, 1 H), 7.30 (dd, J=8.6, 2.4 Hz, 1 H), 7.10-7.06 (m, 1 H), 3.59-3.55 (m, 1 H), 1.25-1.22 (m, 2 H), 0.83-0.80 (m, 2 H). | Fc1cncc(-c2nc3ccc(F)cc3n2C2CC2)c1 | null | null | null |
541,896 | ord_dataset-49124ff635234889bd8dcfe87f4f9013 | null | 2002-01-01T00:04:00 | true | [F:1][C:2]1[CH:3]=[CH:4][C:5]([OH:11])=[C:6]([C:8](=[O:10])[CH3:9])[CH:7]=1.I[CH2:13][CH3:14].C([O-])([O-])=O.[K+].[K+]>CC(C)=O>[CH2:13]([O:11][C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][C:6]=1[C:8](=[O:10])[CH3:9])[CH3:14] | CCI | CC(=O)c1cc(F)ccc1O | null | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(C)=O | null | null | null | null | null | null | null | null | null | null | null | null | 5′-Fluoro-2′-hydroxyacetophenone (9.38 g, 61 mmole), iodoethane (7.3 ml, 91 mmole) and K2CO3 (12.6 g, 91 mmole) in acetone (100 ml) was stirred at 60° C. overnight. The mixture was filtered, evaporated, dissolved in hexane/ethyl acetate, washed with 2M NaOH (2×20 ml) and water, dried (MgSO4) and evaporated to give 2′-ethoxy-5′-fluoroacetophenone. A solution of mCPBA )19.3 g, 112 mmole) in CH2Cl2 (500 ml) was dried with MgSO4. 2′-Ethoxy-5′-fluoro-acetophenone (10.2 g, 56 mmole) was added and the mixture was stirred for 3 days. More mCPBA (5 g, 29 mmole) and MgSO4 was added and stirring was continued for 2 days. The mixture was filtered, diluted with ethyl acetate, washed with 2 M NaOH (2×70 ml), NH4Cl (sat, 50 ml), dried (MgSO4) and evaporated. The residue (10.45 g,) was dissolved in ethanol (100 ml). KOH (8.9 g, 160 mmole) was dissolved in water (50 ml). The solutions were combined and stirred for 1 h. The mixture was washed with diethyl ether/hexane 2×(50+25 ml), acidified with HCl (konc), extracted with ethyl acetate (3×100 ml), dried (MgSO4) and evaporated. The residue (8.22 g) was dissolved in CH2Cl2 (100 ml). Triethylamine 11.7 ml, 84 mmole) and bromomethyl methyl ether (6.45 ml, 79 mmole) were added and the solution was refluxed for 2 hrs. More triethylamine 11.7 ml, 84 mmole) and bromomethyl methyl ether (6.45 ml, 79 mmole) were added and refluxing was continued overnight. The solution was evaporated, CH2Cl (200 ml) was added and the solution was washed with water, 2M NaOH and NH4Cl. Drying (MgSO4) and evaporation provided 4.0 g of 1-ethoxy-4-fluoro-2-methoxymethoxybenzene. This compound was reacted in a manner analogous to Example 39 to give (+,−)-N-(cis-2-(3-ethoxy-6-fluoro-2-methoxymethoxyphenyl)-cyclopropyl)-N′-(5-chloropyrid-2-yl)-urea. Finally deprotection with 2 M HCl in dioxane gave the titled compound. 1NMR (250 MHz, DMSO-D6) δ 1.04-1.14 (m, 1H), 1.41-1.56 (m+t, 4H), 1.96-2.06 (m, 1H), 3.05-3.15 (m, 1H), 4.06-4.19 (m, 2H), 6.64 (t, 1H), 6.94 (dd, 1H), 7.19 (d, 1H), 7.82 (dd, 1H), 8.10 (d, 1H), 8.61 (br.s, 1H), 9.08 (br.s, 1H), 9.57 (br.s, 1H). | CCOc1ccc(F)cc1C(C)=O | null | null | null |
228,725 | ord_dataset-9adbd9cd2fd941f7af27fb31c9bf3bac | null | 1991-01-01T00:06:00 | true | [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=[O:10])=[CH:4][CH:3]=1.CO.S(=O)(=O)(O)O.[C:19]([O-])(O)=O.[Na+]>ClCCCl>[CH3:19][O:10][C:9](=[O:11])[CH2:8][C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=1 | O=C(O)Cc1ccc(Cl)cc1 | O=C([O-])O | null | O=S(=O)(O)O | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | ClCCCl | null | null | null | null | null | null | null | null | null | null | null | 4-Chlorophenylacetic acid (100 g, 0.59 mol) was dissolved in 1,2-dichloroethane (165 ml) and methanol (96 ml, 2.4 moles) and to the solution was added concentrated sulfuric acid (2.75 ml), followed by refluxing for 6 hours. The mixture was cooled and aqueous NaHCO3 was added, followed by stirring. The resulting organic layer was separated, dried over anhydrous sodium sulfate, collected by filtration and concentrated to dryness to obtain methyl-(4-chlorophenyl)-acetate (102 g, yield 94%). | COC(=O)Cc1ccc(Cl)cc1 | null | 94 | null |
1,187,351 | ord_dataset-9cd817a75dfc4fe7ad19d4232772d5ff | null | 2012-01-01T00:07:00 | true | [CH3:1][C:2](=[CH2:37])[C:3]#[C:4][C@@H:5]([N:16]1[CH2:21][CH2:20][C@@H:19]([CH2:22][C:23]([O:25]C)=[O:24])[CH2:18][C@H:17]1[C:27]1[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:29][CH:28]=1)[C:6]1[CH:7]=[N:8][C:9]([C:12]([F:15])([F:14])[F:13])=[CH:10][CH:11]=1.[Li+].[OH-].Cl>C1COCC1.O>[CH3:37][C:2](=[CH2:1])[C:3]#[C:4][C@@H:5]([N:16]1[CH2:21][CH2:20][C@@H:19]([CH2:22][C:23]([OH:25])=[O:24])[CH2:18][C@H:17]1[C:27]1[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:34])[F:35])=[CH:29][CH:28]=1)[C:6]1[CH:7]=[N:8][C:9]([C:12]([F:15])([F:13])[F:14])=[CH:10][CH:11]=1 | C=C(C)C#C[C@H](c1ccc(C(F)(F)F)nc1)N1CC[C@@H](CC(=O)OC)C[C@H]1c1ccc(C(F)(F)F)cc1 | 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 | null | null | A solution of the ester from Step 2 (0.146 g, 0.28 mmol) and LiOH (0.133 g, 5.6 mmol) in THF (3 ml) and water (3 ml) was stirred at rt for 16 hrs. The reaction mixture was acidified to pH6 with 2N HCl and extracted with EtOAc. The combined extracts were washed with brine, dried (MgSO4), filtered and evaporated. The residue was purified by chromatography (silica, 1-2% MeOH/DCM) to give the acid (0.101 g, 71%). 1H NMR (360 MHz, CD3OD): δ 1.26-1.38 (1H, m), 1.51 (1H, q, J 12.1), 1.77 (1H, m), 1.90-1.98 (2H, m), 2.03 (3H, s), 2.24 (2H, d, J 6.9), 2.43-2.57 (2H, m), 3.74 (1H, dd, J 2.6, 11.4), 4.70 (1H, s), 5.39 (1H, m), 5.46 (1H, s), 7.70-7.72 (4H, m), 7.80 (1H, d, J 8.2), 8.17 (1H, d, J 8.1), 8.82 (1H, s). | C=C(C)C#C[C@H](c1ccc(C(F)(F)F)nc1)N1CC[C@@H](CC(=O)O)C[C@H]1c1ccc(C(F)(F)F)cc1 | null | 70.7 | null |
988,053 | ord_dataset-35b56288528641309a040cc2b6710b61 | null | 2010-01-01T00:08:00 | true | Cl[C:2]([O:4][CH2:5][CH3:6])=[O:3].N1C=CC=CC=1.[F:13][C:14]([F:49])([F:48])[C:15]1[CH:16]=[C:17]([CH:41]=[C:42]([C:44]([F:47])([F:46])[F:45])[CH:43]=1)[CH2:18][N:19]([CH:25]1[CH2:31][CH2:30][CH2:29][NH:28][C:27]2[CH:32]=[C:33]([C:37]([F:40])([F:39])[F:38])[C:34]([CH3:36])=[CH:35][C:26]1=2)[C:20]1[NH:24][N:23]=[N:22][N:21]=1>ClCCl>[CH2:5]([O:4][C:2]([N:28]1[CH2:29][CH2:30][CH2:31][CH:25]([N:19]([CH2:18][C:17]2[CH:41]=[C:42]([C:44]([F:47])([F:46])[F:45])[CH:43]=[C:15]([C:14]([F:13])([F:49])[F:48])[CH:16]=2)[C:20]2[NH:24][N:23]=[N:22][N:21]=2)[C:26]2[CH:35]=[C:34]([CH3:36])[C:33]([C:37]([F:39])([F:38])[F:40])=[CH:32][C:27]1=2)=[O:3])[CH3:6] | CCOC(=O)Cl | Cc1cc2c(cc1C(F)(F)F)NCCCC2N(Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1)c1nnn[nH]1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | c1ccncc1 | ClCCl | null | null | null | null | null | null | null | null | null | null | 14 | Add ethyl chloroformate (0.24 mmol) and pyridine (0.24 mmol) to a dichloromethane (5 mL) solution of (3,5-bis-trifluoromethyl-benzyl)-(7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)-(1H-tetrazol-5-yl)-amine (0.045 g, 0.08 mmol). After stirring 14 h, wash the reaction with 5% HCl (3 mL), water (3 mL) and brine (3 mL). Dry the organic portion over sodium sulfate and filter. Chromatograph the crude product, eluting with ethyl acetate/hexane (20-60%), to provide the title compound (0.01 g, 20%) as an oil: MS (ES+): 611 (M+H). | CCOC(=O)N1CCCC(N(Cc2cc(C(F)(F)F)cc(C(F)(F)F)c2)c2nnn[nH]2)c2cc(C)c(C(F)(F)F)cc21 | null | 20.5 | null |
1,274,189 | ord_dataset-d3580a12b15e46cc91aa73f4f1a4a8cc | null | 2013-01-01T00:03:00 | true | CC1OC(CO)C(O)C([O:11][CH:12]2[O:17][CH:16]([CH2:18][O:19]C3OCC(O)C(OC)C3O)[CH:15]([OH:30])[CH:14]([O:31]C)[CH:13]2[OH:33])C1O.Cl>O>[O:11]=[CH:12][C@@H:13]([C@H:14]([C@H:15]([C@@H:16]([CH2:18][OH:19])[OH:17])[OH:30])[OH:31])[OH:33] | COC1C(O)COC(OCC2OC(OC3C(O)C(C)OC(CO)C3O)C(O)C(OC)C2O)C1O | null | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | null | null | null | null | null | null | null | null | null | null | 20 | 24 | 500 kg of galactoarabinan (e.g. FiberAid®) are dissolved or suspended in 4,000-5,000 l of water. The pH is adjusted using approximately 50-60 l hydrochloric acid (30% by weight) to a value in the range from 1.0-1.5. The temperature is adjusted to 100° C. The hydrolysis is carried out for 24 hours (hydrolysis control by means of HPLC). Once the hydrolysis is complete cooling takes place to 50-60° C., with filtration (for example by means of a chamber filter press, for example with the Hyflo filter aid) and neutralization, with the solution or the suspension being passed over an alkaline ion exchanger and then again over an acid ion exchanger and then again over an alkaline ion exchanger. The ion exchangers are rinsed with approximately 2,000 l town water. Then the solution or suspension is concentrated by distillation (to approximately 1,500 l) and made to crystallize. The raw ingredient is centrifuged. 500 l 90% by weight of ethanol (remainder: water) are added to the raw product and agitated for one hour at a temperature of approximately 20° C. Through filtration (for example in a chamber filter press) the flushing liquor is separated from the solid matter. This process is carried out twice. The D-galactose raw product is dissolved for recrystallization (100° C., water, saturated solution), active charcoal is added and then filtration performed, for example via the Hyflo filter aid. From the filtrate the D-galactose can be crystallized again and then centrifuged. If necessary, for further purification, recrystallization can be performed again (saturated solution crystallization). Next, the D-galactose obtained in this way is dried (for example by circulating air or vacuum drying cabinet) and ground to the desired particle size. | O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)CO | null | null | null |
733,706 | ord_dataset-76dd1b78ee414d2da0ed30700ef026f7 | null | 2006-01-01T00:10:00 | true | [I:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([OH:11])=[O:10].[C:12](Cl)(=O)C>CO>[CH3:12][O:10][C:9](=[O:11])[CH2:8][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[I:1] | CC(=O)Cl | O=C(O)Cc1ccccc1I | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | 25 | 3 | 2-Iodophenylacetic acid (1.45 g) was added to a mixture of methanol (100 mL) and acetyl chloride (5 mL). After stirring at room temperature for 3 hours, the solvent was removed and the residue was dried under vacuum giving the desired 2-iodophenylacetic acid methyl ester. Yield=100% | COC(=O)Cc1ccccc1I | null | 100 | null |
751,872 | ord_dataset-844a22e1fcab44a5b59c5e2922b2855a | null | 2007-01-01T00:01:00 | true | [Si:1]([O:8][C@@H:9]1[CH2:14][CH2:13][C@H:12]([NH:15]C(=O)OCC2C=CC=CC=2)[C@H:11]([C:26]([CH3:28])=[CH2:27])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]>CO.[Pd]>[Si:1]([O:8][C@@H:9]1[CH2:14][CH2:13][C@H:12]([NH2:15])[C@H:11]([CH:26]([CH3:28])[CH3:27])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:2])[CH3:3] | C=C(C)[C@@H]1C[C@H](O[Si](C)(C)C(C)(C)C)CC[C@@H]1NC(=O)OCc1ccccc1 | 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 | 4 | Benzyl (1S,2S,4R)-4-(tert-butyldimethylsilyloxy)-2-(prop-1-en-2-yl)cyclohexylcarbamate (4.8 g) in MeOH (40 mL) was charged with 10% Pd/C, Degussa (600 mg). The reaction flask was evacuated and then back-filled with hydrogen; this was repeated three more times. The reaction was stirred under 1 atm of H2 for 4 h and then filtered and concentrated to provide (1S,2S,4R)-4-(tert-butyldimethylsilyloxy)-2-isopropylcyclohexanamine (2.9 g). MS (ES+)=272.3 (M+H)+. | CC(C)[C@@H]1C[C@H](O[Si](C)(C)C(C)(C)C)CC[C@@H]1N | null | 89.8 | null |
1,742,087 | ord_dataset-60a3e71da3174666a50a61dcfa611a9f | null | 2016-01-01T00:07:00 | true | O.[NH2:2][NH2:3].[NH2:4][C:5]1[C:12]([I:13])=[CH:11][C:8]([C:9]#[N:10])=[C:7](S(C)=O)[N:6]=1.O>CC(O)C>[I:13][C:12]1[CH:11]=[C:8]2[C:9]([NH2:10])=[N:3][NH:2][C:7]2=[N:6][C:5]=1[NH2:4] | CS(=O)c1nc(N)c(I)cc1C#N | NN | null | null | 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 | 80 | 3 | 275 μl (2 eq) of hydrazine monohydrate is added to a solution of 872 mg (2.84 mmol) of 6-amino-5-iodo-2-(methylsulfinyl)nicotinonitrile in 11 ml of 2-propanol. The reaction medium is stirred at 80° C. for 3 hours. Water is added and the product is extracted with ethyl acetate. The organic phase is dried on magnesium sulfate, filtered and evaporated. The residue is triturated in a minimum of diisopropyl ether. The solid is filtered to yield 523 mg (67%) of 5-iodo-1H-pyrazolo[3,4-b]pyridin-3,6-diamine in the form of a brown powder. | Nc1nc2[nH]nc(N)c2cc1I | null | 67 | null |
1,623,897 | ord_dataset-35c51552812941cda45194a013d34bb9 | null | 2015-01-01T00:08:00 | true | [CH3:1][N:2]1[CH2:18][CH2:17][C:5]2[N:6]([CH2:14][CH2:15][NH2:16])[C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1.[CH:19]1([C:24](O)=[O:25])[CH2:23][CH2:22][CH2:21][CH2:20]1.C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C1C=CN=CC=1.ClCCl>[CH3:1][N:2]1[CH2:18][CH2:17][C:5]2[N:6]([CH2:14][CH2:15][NH:16][C:24]([CH:19]3[CH2:23][CH2:22][CH2:21][CH2:20]3)=[O:25])[C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1 | Cc1ccc2c(c1)c1c(n2CCN)CCN(C)C1 | O=C(O)C1CCCC1 | 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 | 3 | A mixture of 2-(1,2,3,4-tetrahydro-2,8-dimethylpyrido[4,3-b]indol-5-yl)ethanamine (100 mg, 0.41 mmol), cyclopentane carboxylic acid (46 mg, 0.41 mmol), N,N′-dicyclohexylcarbodiimide (93 mg, 0.45 mmol) and 4-dimethylaminopyridine (55 m g, 0.45 mmol) in dry dichloromethane (2.5 ml) were stirred at room temperature for 3 h. The reaction mixture was filtered through Celite and concentrated to obtain 40 mg of N-(2-(1,2,3,4-tetrahydro-2,8-dimethylpyrido[4,3-b]indol-5-yl)ethyl)cyclopentanecarboxamide as TFA salt after purification by reverse-phase chromatography (C-18, 500 mm×50 mm, Mobile Phase A=0.05% TFA in water, B=0.05% TFA in acetonitrile, Gradient: 10% B to 80% B in 30 min, injection vol. 0.5 ml). 1H NMR (DMSO) 9.98-10.09 (bs, 1H), 7.93 (t, 1H), 7.37 (d, 1H), 7.20 (s, 1H), 7.0 (d, 1H), 4.59-4.63 (m, 1H), 4.2-4.3 (m, 1H), 4.07-4.15 (m, 2H), 3.73-3.84 (m, 2H), 3.07-3.15 (m, 2H), 2.99 (s, 3H), 2.59-2.68 (m, 2H), 2.4-2.48 (m, 1H), 2.38 (s, 3H), 1.4-1.84 (m, 8H). | Cc1ccc2c(c1)c1c(n2CCNC(=O)C2CCCC2)CCN(C)C1 | null | 28.7 | null |
1,030,175 | ord_dataset-83acb82dc5ba4f7aba439b9875aaac43 | null | 2011-01-01T00:02:00 | true | [CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([CH:14]=[O:15])[C@H:10]([CH2:16][OH:17])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].I[CH3:21]>CN(C=O)C>[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([CH:14]=[O:15])[C@H:10]([CH2:16][O:17][CH3:21])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1 | O=CN1CCN(Cc2ccccc2)C[C@H]1CO | 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 | null | 0.08 | To a 0° C. solution of alcohol 22 (0.502 g, 2.14 mmol) in dry DMF (20 mL) was added NaH (95%, 0.154 g, 6.43 mmol) in one portion. After stirring 5 min, iodomethane (0.319 g, 2.25 mmol) was added (drop-wise) and the mixture stirred for 20 min at 0° C. then at ambient temperature for 1.5 h. The excess NaH was destroyed by the careful addition of water and the solution was diluted with 40 mL each of water and saturated NaHCO3. The aqueous mixture was extracted with ether (2×40 mL) and ethyl acetate (2×40 mL). The combined extracts were washed with brine (50 mL), dried (K2CO3) and concentrated to give a brown oil that was purified by column chromatography (silica gel, MeOH:CHCl3, gradient 1:199 to 1:49) to afford 23 as a pale colored oil (0.360 g, 69% yield). 1H NMR (400 MHz, CDCl3): δ 2.00-2.12 (m, 1.3H), 2.18 (dd, J=3.7, 11.7 Hz, 0.7H), 2.80-2.92 (m, 2H), 2.93-3.02 (m, 1H), 3.29-3.38 (m, 3H), 3.41-3.76 (m, 5H), 4.16 (bd, 0.7H), 4.60 (m, 0.3H), 7.25-7.35 (m, 5H), 8.04 (s, 0.7H), 8.07 (s, 0.3H); 13C NMR (100 MHz, CDCl3): δ 36.7, 42.7, 47.0, 52.3, 53.2, 53.7, 54.1, 58.8, 59.0, 62.5, 62.6, 69.5, 70.6, 127.2, 128.3, 128.7, 137.7, 161.3, 161.9. HRMS Calcd. for [C14H20N2O2+H+] 249.1603. Found 249.1598. [α]D25-37.6 (c 0.036, CHCl3). | COC[C@@H]1CN(Cc2ccccc2)CCN1C=O | null | 67.7 | null |
195,841 | ord_dataset-a58d1baeeea441fb9918c10f18f2cdb9 | null | 1989-01-01T00:09:00 | true | Cl.[O:2]1[C:6]2[CH:7]=[CH:8][C:9]([C:11](=O)[CH2:12][CH2:13][C:14]([OH:16])=[O:15])=[CH:10][C:5]=2[CH2:4][CH2:3]1.C1(C)C=CC=CC=1>O.[Zn]>[O:2]1[C:6]2[CH:7]=[CH:8][C:9]([CH2:11][CH2:12][CH2:13][C:14]([OH:16])=[O:15])=[CH:10][C:5]=2[CH2:4][CH2:3]1 | O=C(O)CCC(=O)c1ccc2c(c1)CCO2 | null | null | Cl | [Zn] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Cc1ccccc1 | O | null | null | null | null | null | null | null | null | null | null | 8 | 300 g of zinc and 30 g of mercuric chloride are added with stirring to a mixture containing 510 ml of concentrated hydrochloric acid in 240 ml of water, 141 g of 4-(2,3-dihydro-5-benzofuranyl)-4-oxobutanoic acid obtained above and 300 ml of toluene. The reaction medium is brought to reflux for 6 hours. 150 ml of concentrated hydrochloric acid are added and refluxing is continued overnight. | O=C(O)CCCc1ccc2c(c1)CCO2 | null | null | null |
4,158 | ord_dataset-15ce1bcfb62046d9bec87d32620888d5 | null | 1976-01-01T00:03:00 | true | O.[OH-].[Na+].C([O:7][C:8]1[CH:9]=[CH:10][C:11]2[N:12]([CH2:25][CH3:26])[C:13]3[C:18]([C:19]=2[CH:20]=1)=[CH:17][C:16]([O:21]C(=O)C)=[CH:15][CH:14]=3)(=O)C.Cl>>[CH2:25]([N:12]1[C:13]2[CH:14]=[CH:15][C:16]([OH:21])=[CH:17][C:18]=2[C:19]2[C:11]1=[CH:10][CH:9]=[C:8]([OH:7])[CH:20]=2)[CH3:26] | CCn1c2ccc(OC(C)=O)cc2c2cc(OC(C)=O)ccc21 | 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 | null | null | To 700 ml of water containing 80 g (2.0 mole) of sodium hydroxide is added 85 g (0.27 mole) of N-ethyl-3,6-carbazolediol diacetate. The reaction mixture is heated for one hour then acidified with 3N hydrochloric acid to give N-ethyl-3,6-carbazolediol which is recrystallized from ethanol-water. M.P. 190°-200°C (dec.). | CCn1c2ccc(O)cc2c2cc(O)ccc21 | null | null | null |
600,799 | ord_dataset-82e842e611ef4a05b6e7f9ea0a46d52d | null | 2003-01-01T00:07:00 | true | [C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[C:20]([OH:21])=[CH:19][CH:18]=[C:17]3[C:12]=2[CH:13]=[CH:14][C:15]([CH2:22][NH:23][C:24]([C:26]2[C:30]4[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=4[O:28][C:27]=2[CH2:35][CH2:36][CH2:37][CH3:38])=[O:25])=[CH:16]3)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].Br[CH2:40][C:41]#[N:42].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.C(OCC)(=O)C>[C:1]([C:5]1[CH:6]=[CH:7][C:8]([C:11]2[C:20]([O:21][CH2:40][C:41]#[N:42])=[CH:19][CH:18]=[C:17]3[C:12]=2[CH:13]=[CH:14][C:15]([CH2:22][NH:23][C:24]([C:26]2[C:30]4[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=4[O:28][C:27]=2[CH2:35][CH2:36][CH2:37][CH3:38])=[O:25])=[CH:16]3)=[CH:9][CH:10]=1)([CH3:4])([CH3:3])[CH3:2] | N#CCBr | CCCCc1oc2ccccc2c1C(=O)NCc1ccc2c(-c3ccc(C(C)(C)C)cc3)c(O)ccc2c1 | 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 | 8 | A mixture of 2-butyl-benzofuran-3-carboxylic acid [5-(4-tert-butyl-phenyl)-6-hydroxy-naphthalen-2-ylmethyl]-amide (400 mg, 0.79 mmol), prepared in the previous step, bromoacetonitrile (66 μL, 0.95 mmol) and potassium carbonate (547 mg, 3.96 mmol) in 20 mL of DMF was stirred under nitrogen at room temperature for 19 h (overnight). The reaction was diluted with ethyl acetate, extracted multiple times with water, dried (MgSO4) and the solvent removed under reduced pressure to give a light brown solid. Purification of the solid on a 40 g KP-SIL 60 Δ Biotage column gave 2-butyl-benzofuran-3-carboxylic acid [5-(4-tert-butyl-phenyl)-6-cyanomethoxy-naphthalen-2-ylmethyl]-amide (262 mg, 63%) as a white solid, mp 162-164° C. | CCCCc1oc2ccccc2c1C(=O)NCc1ccc2c(-c3ccc(C(C)(C)C)cc3)c(OCC#N)ccc2c1 | null | 60.9 | null |
924,114 | ord_dataset-cc0899cd744f4f7f8e7f2463560faad1 | null | 2009-01-01T00:12:00 | true | C(ON=O)CC(C)C.[F:9][C:10]1[CH:23]=[CH:22][CH:21]=[CH:20][C:11]=1[O:12][C:13]1[CH:18]=[CH:17][C:16](N)=[CH:15][CH:14]=1.[I:24]CI.O>C(#N)C>[F:9][C:10]1[CH:23]=[CH:22][CH:21]=[CH:20][C:11]=1[O:12][C:13]1[CH:18]=[CH:17][C:16]([I:24])=[CH:15][CH:14]=1 | Nc1ccc(Oc2ccccc2F)cc1 | ICI | null | CC(C)CCON=O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC#N | O | null | null | null | null | null | null | null | null | null | 55 | null | Add isoamylnitrite (2.45 g, 2.5 Eq.) to 4-(2-fluoro-phenoxy)-phenylamine (1.70 g, 8.37 mmol) and diiodomethane (7.84 g, 3.5 Eq.) in acetonitrile (10 mL) while stirring at 55° C. under a nitrogen atmosphere. Slowly heat mixture to 75° C. and heat at this temperature for 3 hours. Cool to room temperature and pour into water, and extract the desired material into ethyl acetate. Wash this organic layer once with water, dry over potassium carbonate, filter, and concentrate under reduced vacuum to give 2.41 g of an oil. Purify the material by silica gel chromatography (Prep. 2000) eluting with hexane/methylene chloride 9:1 to provide 1.60 g of the title compound as a thin oil. Mass spectrum (m/e): 314.0 (M*): (Bruker 300) 1H NMR (CDCl3) δ 7.55-7.60 (2H, d), 7.02-7.20 (4H, m), 6.69-6.72 (2H, d). | Fc1ccccc1Oc1ccc(I)cc1 | null | 91.7 | null |
823,415 | ord_dataset-ec58fad8331a42c5a67ad75aac6713b4 | null | 2008-01-01T00:05:00 | true | [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([CH3:18])([CH2:13][CH2:14][CH:15]([CH3:17])[CH3:16])[C:10](O)=[O:11])=[CH:5][CH:4]=1.C(Cl)(=O)C([Cl:22])=O.CN(C)C=O>ClCCl>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([CH3:18])([CH2:13][CH2:14][CH:15]([CH3:17])[CH3:16])[C:10]([Cl:22])=[O:11])=[CH:5][CH:4]=1 | COc1ccc(C(C)(CCC(C)C)C(=O)O)cc1 | O=C(Cl)C(=O)Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | ClCCl | null | null | null | null | null | null | null | null | null | 0 | 0.5 | To a cooled solution of Example 155C (8.52 g, 0.034 mol) in 200 mL anhydrous dichloromethane was added 2 N oxalyl chloride in dichloromethane (26 mL, 0.052 mol) and drops of dimethylforamide. The solution was stirred for 30 minutes at 0° C. and then room temperature for 2 hours. The solvent was removed under vacuum and the crude product used directly. | COc1ccc(C(C)(CCC(C)C)C(=O)Cl)cc1 | null | null | null |
753,246 | ord_dataset-844a22e1fcab44a5b59c5e2922b2855a | null | 2007-01-01T00:01:00 | true | [Br:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH:5]=[O:6].[CH3:10][N+:11]([O-:13])=[O:12].[OH-].[K+]>CO>[Br:1][C:2]1[CH:3]=[C:4]([C:5](=[O:6])[CH2:10][N+:11]([O-:13])=[O:12])[CH:7]=[CH:8][CH:9]=1 | C[N+](=O)[O-] | O=Cc1cccc(Br)c1 | null | [K+] | [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 | 2 | To a solution of 3-bromobenzaldehyde (18.5 g, 100 mmol) in MeOH (100 mL) was added MeNO2 (12.2 g, 200 mmol) at 0° C. followed by addition of KOH (11.2 g, 200 mmol). After 2 hours, MeOH was removed in vacuo and the resulting mixture was partitioned between ethyl acetate and water. Ethyl acetate extracts were dried over MgSO4 and concentrated to give 20 g crude mixture. This crude mixture was dissolved in AcOH (200 mL), to which CrO3 (12.0 g, 120 mmol) was added. Acetic acid was removed under vacuo after 2 hours and water (200 mL) was added and extracted with ethyl acetate (3×100 mL). The combined organic extracts were dried over MgSO4, filtered and then concentrated under vacuo. dichloromethane (20 mL) was added and the titled compound (8.5 g, 35% for 2 steps) was precipitated out and collected by filtration. | O=C(C[N+](=O)[O-])c1cccc(Br)c1 | null | 82 | null |
1,086,861 | ord_dataset-52a37d876ddb453e86de0c15fa233d29 | null | 2011-01-01T00:09:00 | true | [NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4](=[O:20])[N:5]([CH:12]1[CH2:17][CH2:16][C:15](=[O:18])[NH:14][C:13]1=[O:19])[C:6]2=[O:11].[C:21](Cl)(=[O:26])[CH2:22][CH2:23][CH2:24][CH3:25]>C1COCC1>[O:19]=[C:13]1[CH:12]([N:5]2[C:4](=[O:20])[C:3]3[C:7](=[CH:8][CH:9]=[CH:10][C:2]=3[NH:1][C:21](=[O:26])[CH2:22][CH2:23][CH2:24][CH3:25])[C:6]2=[O:11])[CH2:17][CH2:16][C:15](=[O:18])[NH:14]1 | Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O | CCCCC(=O)Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | null | null | To a stirred suspension of 4-amino-2-(2,6-dioxo(3-piperidyl))isoindoline-1,3-dione (0.55 g, 2.0 mmol) in THF (30 ml) was added pentanoyl chloride (0.48 g, 4.0 mmol). The stirred mixture was heated to reflux for 18 hours. The solvent was evaporated in vacuo and the resulting solid was slurried in diethyl ether (20 ml) and filtered to give 0.61 g (85%) of product as an off-white solid: mp 178-179° C.; 1H NMR (DMSO-d6) δ 11.17 (s, 1H), 9.65 (s, 1H), 8.50 (d, J=8.3 Hz, 1H), 7.82 (t, J=7.5 Hz, 1H), 7.59 (d, J=7.2 Hz, 1H), 5.18 (dd, J=5.0 and 12.4 Hz, 1H), 2.99-2.89 (m, 1H), 2.68-2.45 (m, 4H), 2.13-2.09 (m, 1H), 1.69-1.57 (m, 2H), 1.44-1.30 (m, 2H), 0.92 (t, J=7.2 Hz, 3H); 13C NMR (DMSO-d6) δ 172.72, 171.99, 169.73, 167.83, 166.64, 136.64, 136.07, 131.36, 125.96, 118.15, 116.68, 48.97, 36.32, 30.97, 26.88, 22.03, 21.70, 13.64; Anal. Calcd. For C18H19N3O5: C, 60.50; H, 5.36; N, 11.76. Found: C, 60.10; H, 5.37; N, 11.58. | CCCCC(=O)Nc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O | null | 85.3 | null |
373,092 | ord_dataset-ee5599340390470d8e5b5ac1feddf9d6 | null | 1997-01-01T00:08:00 | true | [C:1]([OH:6])(=[O:5])[C:2]([OH:4])=[O:3].C(O)(=O)C(O)=O.[NH2:13][CH:14]1[CH2:19][CH2:18][N:17]([CH2:20][CH2:21][NH:22][C:23]([C:25]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[N:27]([CH:34]([CH3:36])[CH3:35])[N:26]=2)=[O:24])[CH2:16][CH2:15]1.C(N(CC)CC)C.[C:44](Cl)(=[O:48])[CH2:45][CH2:46][CH3:47]>O1CCCC1>[C:1]([OH:6])(=[O:5])[C:2]([OH:4])=[O:3].[C:44]([NH:13][CH:14]1[CH2:15][CH2:16][N:17]([CH2:20][CH2:21][NH:22][C:23]([C:25]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[N:27]([CH:34]([CH3:36])[CH3:35])[N:26]=2)=[O:24])[CH2:18][CH2:19]1)(=[O:48])[CH2:45][CH2:46][CH3:47] | CC(C)n1nc(C(=O)NCCN2CCC(N)CC2)c2ccccc21 | CCCC(=O)Cl | null | O=C(O)C(=O)O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | CCN(CC)CC | null | null | null | null | null | null | null | null | null | 25 | 18 | The product from Example 23, as the free base (0.330 g, 1 mmol) and triethylamine (0.15 mL, 1.05 mmol) were stirred in 10.0 mL tetrahydrofuran and cooled briefly in an ice bath. To the mixture was added dropwise butyryl chloride (0.1 mL, 1 mmol) and the resulting mixture was stirred 18 h at room temperature and filtered, and the filtrate was evaporated to 0.389 g oil. Crystallization as the oxalate salt from ethyl acetate/methanol provided 0.149 g colorless crystals. Mp 122° C. Mass spectrum, m+ =399. Anal (C24H35N5O6) theory C, 58.88; H, 7.21; N, 14.32; found C, 58.60; H, 7.15; N, 14.30. | CCCC(=O)NC1CCN(CCNC(=O)c2nn(C(C)C)c3ccccc23)CC1 | null | null | null |
832,441 | ord_dataset-47bd90bf5ec74fcd99ce250a56e18c8f | null | 2008-01-01T00:07:00 | true | [Cl:1][C:2]1[NH:3][C:4]2[C:9]([C:10]=1[CH:11]=[O:12])=[CH:8][CH:7]=[CH:6][CH:5]=2.[O:13]([C:20]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][CH:21]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>>[Cl:1][C:2]1[N:3]([C:23]2[CH:24]=[CH:25][C:20]([O:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[CH:21][CH:22]=2)[C:4]2[C:9]([C:10]=1[CH:11]=[O:12])=[CH:8][CH:7]=[CH:6][CH:5]=2 | O=Cc1c(Cl)[nH]c2ccccc12 | OB(O)c1ccc(Oc2ccccc2)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 | 2-Chloro-1H-indole-3-carboxaldehyde is reacted with 4-phenoxyphenylboronic acid as described in Step 1 of Example 29 to afford 2-chloro-1-(4-phenoxyphenyl)-1H-indole-3-carboxaldehyde (34% yield) as a cream solid. ESI/MS 348 (M+H), 389 [(M+1+CH3CN) adduct], RT 3.74 min. | O=Cc1c(Cl)n(-c2ccc(Oc3ccccc3)cc2)c2ccccc12 | null | 34 | null |
1,707,655 | ord_dataset-54347fcace774f89850681d6dec8009f | null | 2016-01-01T00:03:00 | true | [CH:1]1([C:4]2[N:9]=[C:8]([CH:10]=O)[CH:7]=[CH:6][N:5]=2)[CH2:3][CH2:2]1.Cl.NO.C([N:17](CC)CC)C.CCCP(=O)=O>CN(C)C=O.O>[CH:1]1([C:4]2[N:9]=[C:8]([C:10]#[N:17])[CH:7]=[CH:6][N:5]=2)[CH2:3][CH2:2]1 | CCN(CC)CC | O=Cc1ccnc(C2CC2)n1 | null | CCCP(=O)=O | Cl | NO | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | O | null | null | null | null | null | null | null | null | null | 50 | 16 | To a solution of 2-cyclopropylpyrimidine-4-carbaldehyde (1.0 g, 6.68 mmol) in N,N-dimethylformamide (10 mL) were added hydroxylamine hydrochloride (500 mg, 7.02 mmol) and triethylamine (1.2 mL). The reaction mixture was heated to 50° C. and propylphosphonic anhydride (T3P) was added dropwise. After 16 h at 110° C., the mixture was cooled to room temperature, diluted with water and quenched with solid sodium bicarbonate. The mixture was extracted with ethyl acetate, then the organic layer was dried over sodium sulfate, filtered, concentrated under reduced pressure. The residue was purified via silica gel chromatography to afford 2-cyclopropylpyrimidine-4-carbonitrile (600 mg, 62%) as a pale yellow liquid. MS (ES+APCI) (M+H) 145.9; LMCS retention time 2.224 min (Method G). | N#Cc1ccnc(C2CC2)n1 | null | 62 | null |
1,133,074 | ord_dataset-aaeaab5f3720492494c1cbbdd0ed2820 | null | 2012-01-01T00:02:00 | true | [NH2:1][C:2]1[CH:3]=[C:4]2[C:17](=[CH:18][CH:19]=1)[CH2:16][C:6]1([C:14]3[C:9](=[N:10][CH:11]=[CH:12][CH:13]=3)[NH:8][C:7]1=[O:15])[CH2:5]2.Cl[C:21]1[N:26]=[CH:25][N:24]=[C:23]([C:27]([N:29]2[C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[CH2:31][CH:30]2[CH2:38][CH3:39])=[O:28])[CH:22]=1.Cl>CC(O)C>[CH2:38]([CH:30]1[CH2:31][C:32]2[C:37](=[CH:36][CH:35]=[CH:34][CH:33]=2)[N:29]1[C:27]([C:23]1[N:24]=[CH:25][N:26]=[C:21]([NH:1][C:2]2[CH:3]=[C:4]3[C:17](=[CH:18][CH:19]=2)[CH2:16][C:6]2([C:14]4[C:9](=[N:10][CH:11]=[CH:12][CH:13]=4)[NH:8][C:7]2=[O:15])[CH2:5]3)[CH:22]=1)=[O:28])[CH3:39] | Nc1ccc2c(c1)CC1(C2)C(=O)Nc2ncccc21 | CCC1Cc2ccccc2N1C(=O)c1cc(Cl)ncn1 | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(C)O | null | null | null | null | null | null | null | null | null | null | null | null | 103 mg (0.40 mmol) 5-amino-1,3-dihydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one, 113 mg (0.40 mmol) (6-chloro-pyrimidin-4-yl)-(2-ethyl-2,3-dihydro-indol-1-yl)-methanone and 13 μL of a 4 molar aqueous hydrochloric acid solution were added to 2.0 mL of 2-propanol and the mixture was refluxed for 2 h. Then the reaction mixture was evaporated down and purified by preparative HPLC-MS. The product-containing fractions were combined and the organic solvent was evaporated down. The residue was made alkaline with a 1N aqueous sodium hydroxide solution, the precipitate formed was suction filtered, washed with water and dried under HV. | CCC1Cc2ccccc2N1C(=O)c1cc(Nc2ccc3c(c2)CC2(C3)C(=O)Nc3ncccc32)ncn1 | null | null | null |
300,261 | ord_dataset-fb70ed83140e4f53a907d87192ad748c | null | 1994-01-01T00:11:00 | true | [C:1]1([CH2:7][CH:8]=[CH:9][CH:10]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H][H]>C(O)C.[Pd]>[C:1]1([CH2:7][CH2:8][CH2:9][CH:10]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1 | [H][H] | C(=CC1CCCCCCCCCCC1)Cc1ccccc1 | null | [Pd] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | null | null | null | null | null | null | null | null | null | null | null | 8 | To 6.4 g (22.5 mmoles) of 1-(3-phenyl-1-propenyl)cyclododecane in 50 mL of ethanol is added 0.48 g of 10% palladium on carbon. The reaction mixture is subjected to hydrogen (50 psi) atmosphere using a Paar hydrogenerator and shaken overnight after which time no starting material is evident by TLC. The reaction mixture is filtered through Celite which is washed with additional ethanol. The filtrate is evaporated and the crude residue (5.8 g) is used directly for the next step: NMR (CDCl3) δ1.2-1.4 (m, 10H), 1.6 (m, 2H), 2.55 (t, 2H, J=8 Hz), 7.2 (m, 5H). | c1ccc(CCCC2CCCCCCCCCCC2)cc1 | null | null | null |
958,872 | ord_dataset-ed65749688da45af8a8432967b017729 | null | 2010-01-01T00:05:00 | true | [C:1]1([C:7]2[O:8][C:9]([C:15]([F:18])([F:17])[F:16])=[C:10]([C:12]([OH:14])=O)[N:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:19][C:20]1[CH:21]=[N:22][C:23]([N:26]2[CH2:29][C:28]([F:31])([F:30])[CH2:27]2)=[CH:24][CH:25]=1>>[F:31][C:28]1([F:30])[CH2:29][N:26]([C:23]2[N:22]=[CH:21][C:20]([NH:19][C:12]([C:10]3[N:11]=[C:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[O:8][C:9]=3[C:15]([F:18])([F:17])[F:16])=[O:14])=[CH:25][CH:24]=2)[CH2:27]1 | Nc1ccc(N2CC(F)(F)C2)nc1 | O=C(O)c1nc(-c2ccccc2)oc1C(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 | With a method similar to example 16 above, 2-phenyl-5-trifluoromethyloxazole-4-carboxylic acid-[6-(3,3-difluoroazetidin-1-yl)pyridin-3-yl]amide was prepared from 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid and 3-amino-6-(3,3-difluoroazetidin-1-yl)pyridine. LCMS calcd for C19H13F5N4O2 m/e 424.33, obsd 425.0 (ES, M+H). | O=C(Nc1ccc(N2CC(F)(F)C2)nc1)c1nc(-c2ccccc2)oc1C(F)(F)F | null | null | null |
1,249,876 | ord_dataset-c544c0c663f54dbea4ddb52ddde7934e | null | 2013-01-01T00:01:00 | true | C[O:2][C:3](=[O:42])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]([C@H:14]2[C@H:18]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[C:20]=3[F:26])[C@:17]([C:29]3[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][C:30]=3[F:36])([C:27]#[N:28])[C@H:16]([CH2:37][C:38]([CH3:41])([CH3:40])[CH3:39])[NH:15]2)=[O:13])=[CH:7][CH:6]=1.[Li+].[OH-]>C1COCC1.CO>[Cl:25][C:21]1[C:20]([F:26])=[C:19]([C@@H:18]2[C@:17]([C:29]3[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][C:30]=3[F:36])([C:27]#[N:28])[C@H:16]([CH2:37][C:38]([CH3:41])([CH3:40])[CH3:39])[NH:15][C@H:14]2[C:12]([NH:11][C:8]2[CH:7]=[CH:6][C:5]([CH2:4][C:3]([OH:42])=[O:2])=[CH:10][CH:9]=2)=[O:13])[CH:24]=[CH:23][CH:22]=1 | COC(=O)Cc1ccc(NC(=O)[C@@H]2N[C@@H](CC(C)(C)C)[C@](C#N)(c3ccc(Cl)cc3F)[C@H]2c2cccc(Cl)c2F)cc1 | null | null | [Li+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | CO | null | null | null | null | null | null | null | null | null | 25 | 2 | A mixture of (4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-phenyl)-acetic acid methyl ester (72 mg, 0.117 mmol) was dissolved in THF (3 mL) and methanol (1 mL), then 2N LiOH (1 mL) was added and stirred at room temperature for 2 hours. The mixture was concentrated and diluted with water and ethyl acetate. The organic phase was separated then concentrated to yield chiral (4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-phenyl)-acetic acid (37 mg, 52.6%) as an white powder. HRMS (ES+) m/z Calcd for C31H29Cl2F2N3O3+H [(M+H)+]: 600.1627. found: 600.1626. | CC(C)(C)C[C@@H]1N[C@@H](C(=O)Nc2ccc(CC(=O)O)cc2)[C@H](c2cccc(Cl)c2F)[C@@]1(C#N)c1ccc(Cl)cc1F | null | 52.7 | null |
1,410,956 | ord_dataset-7456bda2326f4bebaa874a5474d4cc0d | null | 2014-01-01T00:03:00 | true | [F:1][C:2]1[CH:11]=[C:10]([C:12](=O)[CH3:13])[C:9]([N:15]2[CH2:19][CH2:18][C@@H:17]([OH:20])[CH2:16]2)=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.C([O-])(=O)C.[NH4+].C([BH3-])#[N:27].[Na+]>CO.C(#N)C>[NH2:27][CH:12]([C:10]1[C:9]([N:15]2[CH2:19][CH2:18][C@@H:17]([OH:20])[CH2:16]2)=[C:8]2[C:3]([CH:4]=[CH:5][CH:6]=[N:7]2)=[C:2]([F:1])[CH:11]=1)[CH3:13] | [BH3-]C#N | CC(=O)c1cc(F)c2cccnc2c1N1CC[C@@H](O)C1 | null | CC(=O)[O-] | [NH4+] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | CC#N | null | null | null | null | null | null | null | null | null | 65 | null | A mixture of 1-{5-fluoro-8-[(3R)-3-hydroxypyrrolidin-1-yl]quinolin-7-yl}ethanone (10 mg, 0.04 mmol) and ammonium acetate (28.1 mg, 0.364 mmol) in methanol (0.20 mL) and acetonitrile (0.21 mL) was heated at 65° C. in a sealed tube for 30 minutes. After cooling to room temperature, sodium cyanoborohydride (4.6 mg, 0.073 mmol) was added. The reaction was heated at 65° C. for another 4 hours, then cooled to room temperature and quenched with sat. sodium bicarbonate, extracted with dichloromethane. The combined extracts were dried over magnesium sulfate and evaporated to dryness. The residue was used directly in the next step. LCMS calculated for C15H19FN3O (M+H)+: m/z=276.1; Found: 276.1. | CC(N)c1cc(F)c2cccnc2c1N1CC[C@@H](O)C1 | null | null | null |
1,643,264 | ord_dataset-bcc0b01d4f58457a8733b10a099f43ba | null | 2015-01-01T00:10:00 | true | [N+](=[CH:3][C:4](=[O:13])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([I:12])=[CH:8][CH:7]=1)=[N-].[BrH:14].C(=O)(O)[O-].[Na+]>C(O)(=O)C>[Br:14][CH2:3][C:4](=[O:13])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([I:12])=[CH:8][CH:7]=1 | [N-]=[N+]=CC(=O)Cc1ccc(I)cc1 | Br | null | O=C([O-])O | [Na+] | 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 | 0 | null | 1-Diazo-3-(4-iodophenyl)propan-2-one (13) (1.27 g, 4.43 mmol) was dissolved in acetic acid (20 mL) and cooled to 0° C. To this was added 47% hydrobromic acid (1.55 mL, 13.3 mmol) and stirred for an hour after warming to room temperature. After neutralization by adding saturated aqueous solution of sodium bicarbonate, the product was extracted with ethyl acetate (×3) and the organic layer was washed sequentially with saturated aqueous solution of sodium bicarbonate (×1) and saturated brine (×1), and dried over anhydrous sodium sulfate. After filtration, the mixture was concentrated under reduced pressure and the residue was purified by silica gel flash column chromatography (n-hexane/ethyl acetate=7/1) to give 1-bromo-3-(4-iodophenyl)propan-2-one (16) as a colorless solid (1.42 g, 4.18 mmol, 94.4%). | O=C(CBr)Cc1ccc(I)cc1 | null | 94.4 | null |
1,411,118 | ord_dataset-7456bda2326f4bebaa874a5474d4cc0d | null | 2014-01-01T00:03:00 | true | [CH2:1]([O:4][C:5]1[CH:6]=[C:7]([CH:10]=[CH:11][CH:12]=1)[CH2:8][OH:9])[C:2]#[CH:3].[C:13](OC(=O)C)(=[O:15])[CH3:14]>S(=O)(=O)(O)O.C(Cl)Cl>[C:13]([O:9][CH2:8][C:7]1[CH:10]=[CH:11][CH:12]=[C:5]([O:4][CH2:1][C:2]#[CH:3])[CH:6]=1)(=[O:15])[CH3:14] | C#CCOc1cccc(CO)c1 | CC(=O)OC(C)=O | null | O=S(=O)(O)O | 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 | 0 | 0.5 | A 5.0 L flange flask was charged with 3 (706 g, approx. 4.36 mol, 1 eq) and acetic anhydride (99.5%, ex. Fisher, 1300 ml, 1 mol) to give a clear solution. Sulfuric acid (conc. 98%, 150 drops, ˜3 ml, catalytic) was then added very slowly (dropwise) over 30 minutes, with cooling to 0° C. by aid of an ice/water bath to control the exotherm to give a very dark reaction mixture. Maximum internal temperature observed was 45° C. After the addition the reaction mixture was stirred for 30 min, then the reaction mixture was stirred at 99° C. for 3 h. TLC-examination (silica-gel plate, DCM eluent, PMA stain) showed that all the starting material had been consumed. The mixture was cooled to room temperature (r.t.) overnight to give a dark green solution, which was poured onto an ice-water mixture (2.5 L water and 2.5 Kg of ice) with vigorous stirring. The product was extracted with DCM (5.0 L×3), and the combined extracts washed with water (3.0 L×3), dried over Na2SO4, and evaporated to give a black/brown oily residue. | C#CCOc1cccc(COC(C)=O)c1 | null | null | null |
868,861 | ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b | null | 2009-01-01T00:03:00 | true | Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][CH:3]=1.C([Li])CCC.[CH3:14][O:15][C:16]1[C:17]([S:28](F)(=[O:30])=[O:29])=[CH:18][C:19]2[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21][C:20]=2[CH:27]=1>O1CCCC1>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([S:28]([C:17]2[C:16]([O:15][CH3:14])=[CH:27][C:20]3[CH2:21][CH2:22][N:23]([CH3:26])[CH2:24][CH2:25][C:19]=3[CH:18]=2)(=[O:29])=[O:30])=[CH:3][CH:4]=1 | COc1cc2c(cc1S(=O)(=O)F)CCN(C)CC2 | Brc1ccc(Br)cc1 | null | [Li]CCCC | 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 | 2 | To a stirred solution of 1,4-dibromobenzene (0.665 g, 2.82 mmol, 2.0 eq) in dry tetrahydrofuran (7 mL) under argon at −78° C. was added butyllithium (1.25 mL 2.5M in hexanes, 3.10 mmol, 2.2 eq) dropwise over 10 min. After a further 30 min. a suspension of sulfonyl fluoride D4 (0.385 g, 1.41 mmol, 1.0 eq) was added portionwise. The resultant mixture was allowed to warm to room temperature then stirred for 2 h. The mixture was quenched with water (40 mL) then extracted twice with ethyl acetate (2×40 mL). The organic layer was washed sequentially with water (50 mL) and brine (50 mL) then dried over MgSO4 and evaporated to dryness. Purification by Biotage chromatography, eluting with 1-6% MeOH—CH2Cl2 containing 0.5% NH3 afforded the desired product D13 as a solid, 0.289 g (50%). MH+411. 1H NMR δ (CDCl3) 2.37 (3H, s), 2.55 (4H, m), 2.93 (4H, m), 3.75 (3H, s), 6.65 (1H, s), 7.60 (2H, d), 7.80 (3H, m). | COc1cc2c(cc1S(=O)(=O)c1ccc(Br)cc1)CCN(C)CC2 | null | null | null |
1,024,781 | ord_dataset-136cfada6ce247b4919085a57363459e | null | 2011-01-01T00:01:00 | true | Cl[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1.[C:11]([NH2:15])([CH3:14])([CH3:13])[CH3:12].Cl>CN1C(=O)CCC1>[C:11]([NH:15][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1)([CH3:14])([CH3:13])[CH3:12] | O=[N+]([O-])c1cccnc1Cl | CC(C)(C)N | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN1CCCC1=O | null | null | null | null | null | null | null | null | null | null | 60 | null | To a solution of 2-chloro-3-nitropyridine (5.0 g, 31.53 mmol) in anhydrous NMP (100 mL) was added tert-butylamine (10 mL, 94.52 mmol). The solution was heated at 60° C. for 14 hours and cooled. The mixture was poured into 1N HCl solution (400 mL) and extracted with EtOAc (3×150 mL). The combined organic layers were washed with saturated NaHCO3 solution and dried over MgSO4. After filtration, the solvent was evaporated under vacuum to afford N-tert-butyl-3-nitropyridin-2-amine as dark brown syrup. | CC(C)(C)Nc1ncccc1[N+](=O)[O-] | null | null | null |
191,433 | ord_dataset-d1bd8c96676b4d21aad27b173c6b4eff | null | 1989-01-01T00:06:00 | true | [CH:1]1([CH2:7][N:8]2[C:13](=[O:14])[CH:12]3[C:10]([C:15]4[CH:20]=[CH:19][C:18]([N+:21]([O-])=O)=[CH:17][CH:16]=4)([CH2:11]3)[C:9]2=[O:24])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1>C(O)C.[Pd]>[NH2:21][C:18]1[CH:17]=[CH:16][C:15]([C:10]23[CH2:11][CH:12]2[C:13](=[O:14])[N:8]([CH2:7][CH:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)[C:9]3=[O:24])=[CH:20][CH:19]=1 | O=C1C2CC2(c2ccc([N+](=O)[O-])cc2)C(=O)N1CC1CCCCC1 | null | null | [Pd] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | null | null | null | null | null | null | null | null | null | null | null | null | Following the procedure of Example 3, a solution of 0.5 g of 3-cyclohexylmethyl-1-(4-nitrophenyl)-3-azabicyclo[3.1.0]hexane-2,4-dione in 30 ml of ethanol is hydrogenated in the presence of 0.1 g of 5% palladium on carbon and the reaction mixture is worked up, affording the title compound which melts at 125°-126° C. after recrystallisation from ethyl acetate/petroleum ether. | Nc1ccc(C23CC2C(=O)N(CC2CCCCC2)C3=O)cc1 | null | null | null |
1,053,552 | ord_dataset-373415d3e0e54004837cf4831e67666f | null | 2011-01-01T00:05:00 | true | [OH-].[Na+].C[O:4][C:5](=[O:41])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([CH2:38][CH3:39])([C:22]3[CH:27]=[CH:26][C:25](/[CH:28]=[CH:29]/[C:30]4([OH:36])[CH2:35][CH2:34][S:33][CH2:32][CH2:31]4)=[C:24]([CH3:37])[CH:23]=3)[CH2:20][CH3:21])=[CH:15][C:14]=2[CH3:40])=[CH:9][CH:8]=1>CO.O1CCCC1>[CH2:20]([C:19]([C:16]1[CH:17]=[CH:18][C:13]([C:10]2[CH:11]=[CH:12][C:7]([CH2:6][C:5]([OH:41])=[O:4])=[CH:8][CH:9]=2)=[C:14]([CH3:40])[CH:15]=1)([C:22]1[CH:27]=[CH:26][C:25](/[CH:28]=[CH:29]/[C:30]2([OH:36])[CH2:31][CH2:32][S:33][CH2:34][CH2:35]2)=[C:24]([CH3:37])[CH:23]=1)[CH2:38][CH3:39])[CH3:21] | CCC(CC)(c1ccc(/C=C/C2(O)CCSCC2)c(C)c1)c1ccc(-c2ccc(CC(=O)OC)cc2)c(C)c1 | null | null | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | C1CCOC1 | null | null | null | null | null | null | null | null | null | 25 | 14 | A 1 N sodium hydroxide aqueous solution (0.11 mL, 0.11 mmol) was added to a solution of [4′-(1-ethyl-1-{4-[(E)-2-(4-hydroxy-tetrahydro-thiopyran-4-yl)-vinyl]-3-methyl-phenyl}-propyl)-2′-methyl-biphenyl-4-yl]-acetic acid methyl ester (Example 138-(4); 20 mg, 0.037 mmol) in methanol-tetrahydrofuran (1:1, 2 mL), and the mixture was stirred at room temperature for 14 hours. The reaction mixture was concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (dichloromethane:methanol=10:1) to give the target compound as a colorless oil (15 mg, 77%). | CCC(CC)(c1ccc(/C=C/C2(O)CCSCC2)c(C)c1)c1ccc(-c2ccc(CC(=O)O)cc2)c(C)c1 | null | 76.7 | null |
1,333,295 | ord_dataset-cfad8b3f00044bcda60a96b019f09872 | null | 2013-01-01T00:08:00 | true | [Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:27])[C:7]=1[NH:8][C:9]1[S:10][C:11]2[C:17]3[CH2:18][C:19]([CH3:22])([CH3:21])[O:20][C:16]=3[C:15]([C:23]([O:25]C)=[O:24])=[CH:14][C:12]=2[N:13]=1.[OH-].[Na+]>CO>[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:27])[C:7]=1[NH:8][C:9]1[S:10][C:11]2[C:17]3[CH2:18][C:19]([CH3:22])([CH3:21])[O:20][C:16]=3[C:15]([C:23]([OH:25])=[O:24])=[CH:14][C:12]=2[N:13]=1 | COC(=O)c1cc2nc(Nc3c(Cl)cncc3Cl)sc2c2c1OC(C)(C)C2 | null | null | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | null | null | The title compound was prepared following the procedure described for step-2 of intermediate-3 using methyl 2-[(3,5-dichloropyridin-4-yl)amino]-7,7-dimethyl-7,8-dihydrofuro[2,3-g][1,3]benzothiazole-5-carboxylate (0.080 g, 0.188 mmol), methanol (2.0 mL) and (50%) aqueous solution of sodium hydroxide (0.200 g, 5.00 mmol) to afford 0.050 g of the desired product. 1HNMR (DMSO-d6): δ 1.43 (s, 6H), 2.98 (s, 2H), 7.37 (s, 1H), 7.30 (s, 1H), 8.61 (m, 2H), 12-13 (s, 1H); MS [M+H]+: 424.18. | CC1(C)Cc2c(c(C(=O)O)cc3nc(Nc4c(Cl)cncc4Cl)sc23)O1 | null | 64.8 | null |
203,336 | ord_dataset-76a008eb2d3f48d891cad325041f3d1e | null | 1990-01-01T00:02:00 | true | [CH3:1][S:2](Cl)(=[O:4])=[O:3].[OH:6][CH2:7][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[N:11]=[CH:10][CH:9]=1.C(N(CC)CC)C>C(Cl)Cl>[CH3:1][S:2]([O:6][CH2:7][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[N:11]=[CH:10][CH:9]=1)(=[O:4])=[O:3] | CS(=O)(=O)Cl | OCc1ccnc2ccccc12 | 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 | A solution of methanesulfonyl chloride (4.84 ml) in 20 ml of methylene chloride is slowly added over 20 minutes to a solution of 8.29 g of 4-hydroxymethylquinoline and 11 ml of triethylamine in 200 ml of methylene chloride at 0°. After completion of the reaction at room temperature, the reaction mixture is partitioned between methylene chloride and saturated potassium carbonate solution. The organic layer is dried over sodium sulfate and evaporated to dryness to yield 4-(methanesulfonyloxymethyl)quinoline as an oil. | CS(=O)(=O)OCc1ccnc2ccccc12 | null | null | null |
1,246,915 | ord_dataset-c544c0c663f54dbea4ddb52ddde7934e | null | 2013-01-01T00:01:00 | true | Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:15][CH2:14][N:13]([C:16]3[C:21]([CH3:22])=[CH:20][C:19]([CH3:23])=[CH:18][N:17]=3)[CH2:12][CH2:11]2)=[O:9])=[C:4]([N:24]2[CH2:28][CH2:27][CH2:26][S:25]2(=[O:30])=[O:29])[CH:3]=1.[CH3:31][C:32]1([CH3:38])[CH2:36][O:35][C:34](=[O:37])[NH:33]1>>[CH3:22][C:21]1[C:16]([N:13]2[CH2:14][CH2:15][N:10]([C:8]([C:5]3[CH:6]=[CH:7][C:2]([N:33]4[C:32]([CH3:38])([CH3:31])[CH2:36][O:35][C:34]4=[O:37])=[CH:3][C:4]=3[N:24]3[CH2:28][CH2:27][CH2:26][S:25]3(=[O:30])=[O:29])=[O:9])[CH2:11][CH2:12]2)=[N:17][CH:18]=[C:19]([CH3:23])[CH:20]=1 | CC1(C)COC(=O)N1 | Cc1cnc(N2CCN(C(=O)c3ccc(Br)cc3N3CCCS3(=O)=O)CC2)c(C)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | By reaction and treatment in the same manner as in Example 1 and using [4-bromo-2-(1,1-dioxoisothiazolidin-2-yl)phenyl][4-(3,5-dimethylpyridin-2-yl)piperazin-1-yl]methanone (247 mg) described in Preparation Example 118 and 4,4-dimethyloxazolidin-2-one (57.6 mg), the title compound (63.6 mg) was obtained. | Cc1cnc(N2CCN(C(=O)c3ccc(N4C(=O)OCC4(C)C)cc3N3CCCS3(=O)=O)CC2)c(C)c1 | null | 24.1 | null |
868,348 | ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b | null | 2009-01-01T00:03:00 | true | [F:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].[C:12](OC(=O)C)(=[O:14])[CH3:13]>>[F:1][C:2]1[CH:8]=[CH:7][C:5]([NH:6][C:12](=[O:14])[CH3:13])=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10] | CC(=O)OC(C)=O | Nc1ccc(F)c([N+](=O)[O-])c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | 25 | 2 | 4-Fluoro-3-nitro-aniline (45.0 g, 288.2 mmol) was added portionwise to acetic anhydride (150 mL) at room temperature. The reaction mixture was stirred at room temperature for 2 h. The white solid was collected and dried in vacuo to give the desired title compound (42.0 g, 70%). | CC(=O)Nc1ccc(F)c([N+](=O)[O-])c1 | null | 70 | null |
901,024 | ord_dataset-de6bce51790e4004a27e1a8f2bcc7ded | null | 2009-01-01T00:08:00 | true | [CH2:1]([C:8]1[CH:26]=[CH:25][CH:24]=[CH:23][C:9]=1[C:10]([NH:12][NH:13][C:14](=[O:22])[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([CH3:21])[CH:16]=1)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O=S(Cl)Cl>C1C=CC=CC=1>[CH2:1]([C:8]1[CH:26]=[CH:25][CH:24]=[CH:23][C:9]=1[C:10]1[O:22][C:14]([C:15]2[CH:16]=[C:17]([CH3:21])[CH:18]=[CH:19][CH:20]=2)=[N:13][N:12]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1 | Cc1cccc(C(=O)NNC(=O)c2ccccc2Cc2ccccc2)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O=S(Cl)Cl | c1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | To a solution of 19 (1.1 g, 3.194 mmol) in 4 mL benzene was added SOCl2 (2.2 mL, 30.13 mmol). The mixture was heated to reflux overnight and then solvent and excess SOCl2 were evaporated. The yellow residue was dissolved in EtOAc. The organic layer was washed with saturated NaHCO3 aqueous solution, H2O and brine, dried over MgSO4 and concentrated. The crude product was purified by flash column chromatography (8-10% EtOAc in n-hexane) to give 2-(2-benzyl-phenyl)-5-m-tolyl-[1,3,4]-oxadiazole 21 (1.0 g, 3.064 mmol, 96% yield). | Cc1cccc(-c2nnc(-c3ccccc3Cc3ccccc3)o2)c1 | null | 95.9 | null |
1,566,623 | ord_dataset-4e54080057a44c3887653391e24c90b6 | null | 2015-01-01T00:03:00 | true | C[O:2][C:3](=[O:38])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH2:12][CH2:13][CH2:14][N:15]([CH2:24][CH:25]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([I:23])[CH:18]=2)[CH:6]=1.[OH-].[Na+]>CO>[C:26]1([CH:25]([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH2:24][N:15]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([I:23])[CH:18]=2)[CH2:14][CH2:13][CH2:12][O:11][C:7]2[CH:6]=[C:5]([CH2:4][C:3]([OH:38])=[O:2])[CH:10]=[CH:9][CH:8]=2)[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1 | COC(=O)Cc1cccc(OCCCN(Cc2cccc(I)c2)CC(c2ccccc2)c2ccccc2)c1 | null | null | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | 25 | 8 | A solution of (3-{3-[(2,2-Diphenyl-ethyl)-(3-iodo-benzyl)-amino]-propoxy}-phenyl)-acetic acid methyl ester (4f). (0.5 g, 0.0008 mol) in methanol (7.5 mL) was treated with 2N NaOH (5 mL) and the mixture stirred overnight at ambient temperature. After concentration to dryness, the residue was dissolved in EtOAc (25 mL) and water was added (10 mL), the solution acidified to pH 3 with concentrated hydrochloric acid, then extracted into EtOAc (3×20 mL). The combined organic extracts were dried over Na2SO4, and then concentrated in vacuo to provide the carboxylic acid as waxy oil, which was purified by flash chromatography (9:1 CH2Cl2/MeOH) to give the desired product as oil 0.32 g in 67% yield. 1H NMR (CD3OD) δ 7.92 (s, 1H), 7.53 (d, 2H), 7.27 (m, 8H), 7.19 (t, 2H), 6.93 (t, 1H), 6.88 (d, 1H), 6.67 (s, 1H), 6.64 (d, 1H), 4.25 (t, 1H), 3.70 (s, 2H), 3.65 (t, 2H), 3.58 (s, 2H), 3.16 (d, 2H), 2.69 (t, 2H), 1.86 (t, 2H); 13C NMR (CD3OD) δ 175.7, 160.4, 144.8, 144.7, 143.2, 139.3, 137.3, 137.2, 137.1, 131.0, 130.9, 130.4, 129.5, 129.3, 127.4. 122.5, 122.4, 116.6, 114.3, 94.9, 66.5, 60.7, 59.5, 51.7, 50.9, 42.2, 27.7. Anal. Calcd for C32H32INO3.H2O: C, 61.62; H, 5.17; I, 20.34; N, 2.25. Found: C, 61.70; H, 5.06; I, 20.68; N, 2.74. | O=C(O)Cc1cccc(OCCCN(Cc2cccc(I)c2)CC(c2ccccc2)c2ccccc2)c1 | null | 67 | null |
103,941 | ord_dataset-1c61a371eaf841328cc190a0356d6b3b | null | 1983-01-01T00:03:00 | true | [H-].[Na+].[CH3:3][O:4][C:5](=[O:23])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][N:13]1[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[NH:15][C:14]1=[O:22].[Cl:24][C:25]1[CH:32]=[CH:31][C:28]([CH2:29]Cl)=[CH:27][CH:26]=1>CN(C=O)C>[CH3:3][O:4][C:5](=[O:23])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][N:13]1[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[N:15]([CH2:29][C:28]2[CH:31]=[CH:32][C:25]([Cl:24])=[CH:26][CH:27]=2)[C:14]1=[O:22] | ClCc1ccc(Cl)cc1 | COC(=O)CCCCCCCn1c(=O)[nH]c2ccccc21 | null | [H-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | null | null | The product is produced as described in example 1 from 0.72 g. of NaH (80% suspension in mineral oil), 7 g. of 8-(2-oxo-benzimidazolin-1-yl)-caprylic acid methyl ester, 100 cc. of DMF, 3.9 g. of 4-chlorobenzylchloride and 0.72 g. of NaJ Eluant in chromatographic purification: hexane/ethylacetate. | COC(=O)CCCCCCCn1c(=O)n(Cc2ccc(Cl)cc2)c2ccccc21 | null | null | null |
1,481,510 | ord_dataset-c3c1091f873b4f40827973a6f1f9b685 | null | 2014-01-01T00:09:00 | true | [NH2:1][CH:2]([C:4]1[N:9]=[C:8]2[CH:10]=[CH:11][N:12]([CH3:13])[C:7]2=[CH:6][C:5]=1[N:14]1[CH2:19][CH2:18][C:17]([CH3:21])([OH:20])[CH2:16][CH2:15]1)[CH3:3].[NH2:22][C:23]1[N:28]=[C:27]([NH2:29])[C:26]([C:30]#[N:31])=[C:25](Cl)[N:24]=1.CCN(CC)CC>CN(C=O)C>[NH2:22][C:23]1[N:28]=[C:27]([NH2:29])[C:26]([C:30]#[N:31])=[C:25]([NH:1][CH:2]([C:4]2[N:9]=[C:8]3[CH:10]=[CH:11][N:12]([CH3:13])[C:7]3=[CH:6][C:5]=2[N:14]2[CH2:15][CH2:16][C:17]([OH:20])([CH3:21])[CH2:18][CH2:19]2)[CH3:3])[N:24]=1 | N#Cc1c(N)nc(N)nc1Cl | CC(N)c1nc2ccn(C)c2cc1N1CCC(C)(O)CC1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(CC)CC | CN(C)C=O | null | null | null | null | null | null | null | null | null | 90 | 8 | To a 10 mL vial were added 1-(5-(1-aminoethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)-4-methylpiperidin-4-ol (56 mg, 0.194 mmol), 2,4-diamino-6-chloropyrimidine-5-carbonitrile (32.9 mg, 0.194 mmol) and Et3N (0.054 mL, 0.388 mmol) in DMF (3 mL). The resulting yellow solution was heated to 90° C. and stirred overnight. The reaction mixture was purified by preparative HPLC eluting with 5-30% ACN in water (with 0.05% ammonium carbonate). The fractions containing the desired product were combined and lyophilized to give the title compound (racemate) as a white solid (40 mg, 49%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.17-1.29 (m, 3 H), 1.32-1.43 (m, 3 H), 1.52-1.87 (m, 4 H), 2.57-2.72 (m, 2 H), 2.73-2.94 (m, 2 H), 3.16-3.29 (m, 1 H), 3.71-3.86 (m, 3 H), 4.24-4.32 (m, 1 H), 5.74-5.88 (m, 1 H), 6.34-6.44 (m, 2 H), 6.44-6.52 (m, 1 H), 6.53-6.65 (m, 3 H), 7.48-7.58 (m, 1 H), 7.77-7.84 (m, 1 H); ESI-MS m/z [M+H]+ calc'd for C21H27N9O, 422.2; found 422.5. | CC(Nc1nc(N)nc(N)c1C#N)c1nc2ccn(C)c2cc1N1CCC(C)(O)CC1 | null | 48.9 | null |
1,418,381 | ord_dataset-f8e6e6a2d2bf4135b9e346456c81700f | null | 2014-01-01T00:04:00 | true | [CH3:1][C:2]1[C:3]([C:12]([OH:14])=O)=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:39][C:40]([F:58])([F:57])[O:41][C:42]1[CH:47]=[CH:46][C:45]([S:48]([N:51]2[CH2:56][CH2:55][NH:54][CH2:53][CH2:52]2)(=[O:50])=[O:49])=[CH:44][CH:43]=1.CCN(C(C)C)C(C)C>CN(C)C=O>[CH3:1][C:2]1[C:3]([C:12]([N:54]2[CH2:53][CH2:52][N:51]([S:48]([C:45]3[CH:46]=[CH:47][C:42]([O:41][C:40]([F:57])([F:58])[F:39])=[CH:43][CH:44]=3)(=[O:49])=[O:50])[CH2:56][CH2:55]2)=[O:14])=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2 | O=S(=O)(c1ccc(OC(F)(F)F)cc1)N1CCNCC1 | Cc1c(C(=O)O)ccc2cccnc12 | null | CN(C)C(On1nnc2cccnc21)=[N+](C)C | F[P-](F)(F)(F)(F)F | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(C(C)C)C(C)C | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | 0.33 | To the solution of 8-methyl-7-quinolinecarboxylic acid (may be prepared as described in Intermediate 2; 90 mg, 0.483 mmol) in N,N-Dimethylformamide (DMF) (2 ml), HATU (193 mg, 0.508 mmol) was added at room temperature. The reaction was stirred for 20 min and then 1-({4-[(trifluoromethyl)oxy]phenyl}sulfonyl)piperazine (may be prepared as described in Intermediate 11; 150 mg, 0.483 mmol) was added followed by DIPEA (0.211 ml, 1.209 mmol) and the reaction mixture was stirred for 3 hours. The reaction mixture was poured into the separating funnel and partitioned between ethyl acetate (25 ml) and sodium hydroxide (15 ml). The organic phase was washed with sodium hydroxide (2×10 ml), water (2×10 ml) and brine (10 mL) before it was dried using phase separator and the solvent was removed under vacuum. The crude product was purified by MDAP to give the title compound as a white solid (115 mg). | Cc1c(C(=O)N2CCN(S(=O)(=O)c3ccc(OC(F)(F)F)cc3)CC2)ccc2cccnc12 | null | 49.7 | null |
182,868 | ord_dataset-f25e1b7f8ef54305a5170f5395a768c7 | null | 1989-01-01T00:01:00 | true | [CH2:1]([N:3]([CH2:17][CH2:18]OS(C1C=CC(C)=CC=1)(=O)=O)[S:4]([C:7]1[C:8]2[CH:9]=[CH:10][N:11]=[CH:12][C:13]=2[CH:14]=[CH:15][CH:16]=1)(=[O:6])=[O:5])[CH3:2].[CH2:30]([NH2:36])[CH2:31][CH2:32][CH2:33][CH2:34][CH3:35].C(=O)([O-])[O-].[K+].[K+].O1CCOCC1>ClCCl>[CH2:1]([N:3]([CH2:17][CH2:18][NH:36][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH3:35])[S:4]([C:7]1[C:8]2[CH:9]=[CH:10][N:11]=[CH:12][C:13]=2[CH:14]=[CH:15][CH:16]=1)(=[O:5])=[O:6])[CH3:2] | CCCCCCN | CCN(CCOS(=O)(=O)c1ccc(C)cc1)S(=O)(=O)c1cccc2cnccc12 | null | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1COCCO1 | ClCCl | null | null | null | null | null | null | null | null | null | 110 | null | To 3.96 g of the thus obtained N-ethyl-N-(2-p-toluenesulfonyloxyethyl)-5-isoquinolinesulfonamide were added 1.25 g of hexylamine, 1.14 g of potassium carbonate and 20 ml of dioxane. The mixture thus obtained was heated in a pressure vessel at 110° C. for 72 hours, and then the dioxane was removed under reduced pressure to obtain a crude product. Then, 60 ml of dichloromethane was added to the crude product, and the mixture thus obtained was washed with 30 ml of water and dried with anhydrous magnesium sulfate. The dichloromethane was removed under reduced pressure to obtain a residue. The residue thus obtained was subjected to purification by silica gel column chromatography (Wacogel C-200, solvent: a 5% methanol solution in chloroform) to obtain 2.50 g of N-ethyl-N-(2-hexylaminoethyl)-5-isoquinolinesulfonamide [Compound (28)]. Compound (28) was analyzed to give the following data. | CCCCCCNCCN(CC)S(=O)(=O)c1cccc2cnccc12 | null | null | null |
491,941 | ord_dataset-3f9174c7efcb4f31becbd3516cde9572 | null | 2001-01-01T00:02:00 | true | [C:1]1([CH2:7][CH2:8][CH2:9][NH:10][CH:11]2[CH2:16][CH2:15][C:14](=[O:17])[CH2:13][CH2:12]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([O-])([O-])=O.[K+].[K+].Cl[C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26].C(Cl)Cl>O>[CH2:28]([O:27][C:25](=[O:26])[N:10]([CH:11]1[CH2:16][CH2:15][C:14](=[O:17])[CH2:13][CH2:12]1)[CH2:9][CH2:8][CH2:7][C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1 | O=C(Cl)OCc1ccccc1 | O=C1CCC(NCCCc2ccccc2)CC1 | null | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | O | null | null | null | null | null | null | null | null | null | null | 1.5 | A mixture of 4-(3-phenyl-propylamino)-cyclohexanone (1.9 g, 8.21 mmol), K2CO3 (1.15 g, 8.3 mmol), benzyl chloroformate (1.42 g, 8.3 mmol) and CH2Cl2 (20 ml) was stirred at r.t for 1.5 h. H2O (50 ml) was added, and the mixture was extracted with CH2Cl2. The organic layer was dried (Na2SO4), evaporated and the residue was purified by chromatography (SiO2, CH2Cl2—MeOH 95:5) to give (4-Oxo-cyclohexyl)-(3-phenyl-propyl)-carbamic acid benzyl ester as a yellow oil (2.7 g, 90%, MS: m/e=365(M+)). | O=C1CCC(N(CCCc2ccccc2)C(=O)OCc2ccccc2)CC1 | null | null | null |
1,153,966 | ord_dataset-b195433d5c354ddfb6cde0d53c41910f | null | 2012-01-01T00:04:00 | true | [N+](C1C=CC(O[C:9]([O:11][C:12]2[CH:13]=[C:14]([CH:19]=[CH:20][CH:21]=2)[C:15]([O:17][CH3:18])=[O:16])=[O:10])=CC=1)([O-])=O.[F:24][C:25]1[CH:26]=[C:27]([CH:31]2[CH:36]([CH2:37][N:38]([C@@H:46]([C:48]3[C:57]4[C:52](=[CH:53][CH:54]=[CH:55][CH:56]=4)[CH:51]=[CH:50][CH:49]=3)[CH3:47])[C:39](=[O:45])[O:40][C:41]([CH3:44])([CH3:43])[CH3:42])[CH2:35][CH2:34][NH:33][CH2:32]2)[CH:28]=[CH:29][CH:30]=1.C1COCC1.C(=O)([O-])O.[Na+]>C(N(CC)CC)C>[C:41]([O:40][C:39]([N:38]([CH2:37][CH:36]1[CH2:35][CH2:34][N:33]([C:9]([O:11][C:12]2[CH:21]=[CH:20][CH:19]=[C:14]([C:15]([O:17][CH3:18])=[O:16])[CH:13]=2)=[O:10])[CH2:32][CH:31]1[C:27]1[CH:28]=[CH:29][CH:30]=[C:25]([F:24])[CH:26]=1)[C@@H:46]([C:48]1[C:57]2[C:52](=[CH:53][CH:54]=[CH:55][CH:56]=2)[CH:51]=[CH:50][CH:49]=1)[CH3:47])=[O:45])([CH3:42])([CH3:43])[CH3:44] | COC(=O)c1cccc(OC(=O)Oc2ccc([N+](=O)[O-])cc2)c1 | C[C@H](c1cccc2ccccc12)N(CC1CCNCC1c1cccc(F)c1)C(=O)OC(C)(C)C | null | O=C([O-])O | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(CC)CC | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | 8 | To a suspension of 5.000 g of methyl 3-hydroxybenzoate, 6.955 g of 4-nitrophenyl chloroformate, and 100 mL of toluene was added 4.81 mL of triethylamine at room temperature, followed by stirring overnight. The insolubles were removed by filtration, and as solvent was removed by distillation under reduced pressure to obtain 5.948 g of methyl 3-{[(4-nitrophenoxy)carbonyl]oxy}benzoate as a pale yellow solid. To a mixture of 100 mg of methyl 3-{[(4-nitrophenoxy)carbonyl]oxy}benzoate, 139 mg of tert-butyl {[3-(3-fluorophenyl)piperidin-4-yl]methyl}[(1R)-1-(1-naphthyl)ethyl]carbamate, and 4 ml of THF was added 0.084 mL of triethylamine at room temperature, followed by stirring overnight. A saturated aqueous sodium hydrogen carbonate solution was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure to obtain 196 mg of 3-(methoxycarbonyl)phenyl 4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-(3-fluorophenyl)piperidine-1-carboxylate as a pale yellow oily compound. | COC(=O)c1cccc(OC(=O)N2CCC(CN(C(=O)OC(C)(C)C)[C@H](C)c3cccc4ccccc34)C(c3cccc(F)c3)C2)c1 | null | 101.8 | null |
165,187 | ord_dataset-12ef86aced0149e0917be82ce22190e2 | null | 1987-01-01T00:11:00 | true | [C:1]1([CH2:7][CH2:8][CH2:9][C:10]2[S:14][C:13]([CH2:15][CH2:16][CH2:17][CH2:18][C:19]([OH:21])=[O:20])=[CH:12][CH:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[CH2:23](O)[CH3:24]>>[C:1]1([CH2:7][CH2:8][CH2:9][C:10]2[S:14][C:13]([CH2:15][CH2:16][CH2:17][CH2:18][C:19]([O:21][CH2:23][CH3:24])=[O:20])=[CH:12][CH:11]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1 | CCO | O=C(O)CCCCc1ccc(CCCc2ccccc2)s1 | 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 | 25 | 24 | 3 g of 5-[5-(3-phenylpropyl)-thien-2-yl]-valeric acid are dissolved in 10 ml of ethanol and the solution is saturated with HCl gas. The solution is stirred at room temperature for 24 hours and concentrated in vacuo. Purification by column chromatography (silica gel/hexane/ethyl acetate). | CCOC(=O)CCCCc1ccc(CCCc2ccccc2)s1 | null | null | null |
1,492,343 | ord_dataset-366bdd9ee72d474cbe6f3f9e54dd96d2 | null | 2014-01-01T00:10:00 | true | [NH2:1][C:2]1[C:3]([O:8][CH2:9][CH2:10][OH:11])=[N:4][CH:5]=[CH:6][CH:7]=1.[CH3:12][O:13][C:14]([C:16]1[S:25][C:19]2[N:20]=[C:21](Cl)[N:22]=[CH:23][C:18]=2[C:17]=1[CH3:26])=[O:15]>>[CH3:12][O:13][C:14]([C:16]1[S:25][C:19]2[N:20]=[CH:21][N:22]=[C:23]([NH:1][C:2]3[C:3]([O:8][CH2:9][CH2:10][OH:11])=[N:4][CH:5]=[CH:6][CH:7]=3)[C:18]=2[C:17]=1[CH3:26])=[O:15] | Nc1cccnc1OCCO | COC(=O)c1sc2nc(Cl)ncc2c1C | null | null | null | null | null | null | null | 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 analogously to example 28.1 from 2-(3-aminopyridin-2-yloxy)ethanol (175 mg) and chloro-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylic acid methyl ester (121 mg) | COC(=O)c1sc2ncnc(Nc3cccnc3OCCO)c2c1C | null | null | null |
1,400,862 | ord_dataset-12dc3bd21bcf44d09e5b4249afe15161 | null | 2014-01-01T00:02:00 | true | [F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:13]=[C:14]4[C:20]([C:21]([NH:23][C:24]([CH3:36])([CH3:35])[CH2:25][CH2:26][NH:27]C(=O)OC(C)(C)C)=[O:22])=[CH:19][NH:18][C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.[F:37][C:38]([F:43])([F:42])[C:39]([OH:41])=[O:40]>ClCCl>[F:37][C:38]([F:43])([F:42])[C:39]([OH:41])=[O:40].[NH2:27][CH2:26][CH2:25][C:24]([NH:23][C:21]([C:20]1[C:14]2[C:15](=[N:16][CH:17]=[C:12]([C:6]3[C:5]4[C:9](=[CH:10][C:2]([F:1])=[CH:3][CH:4]=4)[N:8]([CH3:11])[N:7]=3)[N:13]=2)[NH:18][CH:19]=1)=[O:22])([CH3:35])[CH3:36] | Cn1nc(-c2cnc3[nH]cc(C(=O)NC(C)(C)CCNC(=O)OC(C)(C)C)c3n2)c2ccc(F)cc21 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | O=C(O)C(F)(F)F | null | null | null | null | null | null | null | null | null | null | 1 | To a stirred solution of tert-butyl 3-(2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)-3-methylbutylcarbamate (110 mg, 0.22 mmol) in 6 mL of dichloromethane was added trifluoroacetic acid (3 mL) in one portion at room temperature and the solution stirred for one hour. The solvent was evaporated at 40° C. under reduced pressure and the residue was purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; the gradient conditions were: 20% acetonitrile/80% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 50% acetonitrile/50% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.) to give N-(4-amino-2-methylbutan-2-yl)-2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide 2,2,2-trifluoroacetate (35 mg, 30.9%) as a yellow solid. MS: (M+H)+=396; 1H NMR (300 MHz, DMSO): δ 12.94 (s, 1H), 9.11 (s, 1H), 8.50-8.43 (m, 2H), 7.89 (s, 1H), 7.74-7.70 (m, 3H), 7.70-7.21 (m, 1H), 4.18 (s, 3H), 2.90 (brs, 2H), 2.31-2.26 (m, 2H), 1.53 (s, 6H). | Cn1nc(-c2cnc3[nH]cc(C(=O)NC(C)(C)CCN)c3n2)c2ccc(F)cc21 | null | 30.9 | null |
1,529,188 | ord_dataset-8c74302143c04eb9983e4b3a7ead2d72 | null | 2014-01-01T00:12:00 | true | [Br:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[N:12]=[CH:13][N:14]([CH:16]3[CH2:21][CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18][CH2:17]3)[CH:15]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1>FC(F)(F)C(O)=O>[Br:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[N:12]=[CH:13][N:14]([CH:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)[CH:15]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1 | Cn1cc(Br)cc(Nc2cn(C3CCN(C(=O)OC(C)(C)C)CC3)cn2)c1=O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O=C(O)C(F)(F)F | null | null | null | null | null | null | null | null | null | null | 25 | 1 | A mixture of 243d (2.2 g, 4.88 mmol) and trifluoroacetic acid (20 mL) was stirred at room temperature for 1 h. It was then concentrated under reduced pressure to afford crude 243e (1.5 g, 88%), which was used in the next step without further purification. MS-ESI: [M+H]+ 352.2 | Cn1cc(Br)cc(Nc2cn(C3CCNCC3)cn2)c1=O | null | 87.3 | null |
423,849 | ord_dataset-1a231de00bfe4443b547e1f03885ed41 | null | 1999-01-01T00:01:00 | true | O1CCCC1.[NH:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]([CH2:15][C@@H:16]2[NH:21][CH2:20][CH2:19][N:18]([CH2:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:17]2=O)=[CH:7]1.[OH-].[Na+]>O>[NH:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]([CH2:15][C@@H:16]2[NH:21][CH2:20][CH2:19][N:18]([CH2:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH2:17]2)=[CH:7]1 | O=C1[C@H](Cc2c[nH]c3ccccc23)NCCN1CCc1ccccc1 | null | null | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | C1CCOC1 | null | null | null | null | null | null | null | null | null | 25 | 24 | Combine lithiium aluminumhydride (100 mmol) and tetrahydrofuran (75 ml). Add (S)-3-(1H-Indol-3-ylmethyl)-1-(2-phenyl-ethyl)-2-oxo-piperazine (25 mmol) portionwise. Heat to reflux. After 24 hours, cool to ambient temperature. Carefully add water (3.8 mL), 15% aqueous sodium hydroxide solution (3.8 mL), and water (10.5 mL). Stir vigourously for 1 hour. Filter, rinse the filter cake repeatedly with tetrahydrofuran. Concentrate the filtrate in vacuo to obtain a residue. Chromatograph the residue to give the title compound. | c1ccc(CCN2CCN[C@@H](Cc3c[nH]c4ccccc34)C2)cc1 | null | null | null |
868,221 | ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b | null | 2009-01-01T00:03:00 | true | [Br:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]3[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=3[CH:10]=2)[CH:5]=[N+:4]([O-])[CH:3]=1.O=P(Cl)(Cl)[Cl:19].C(=O)(O)[O-].[Na+]>C(Cl)(Cl)Cl>[Br:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]3[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=3[CH:10]=2)[C:5]([Cl:19])=[N:4][CH:3]=1 | O=P(Cl)(Cl)Cl | [O-][n+]1cc(Br)c2cc3ccccc3cc2c1 | null | O=C([O-])O | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClC(Cl)Cl | null | null | null | null | null | null | null | null | null | null | 55 | 2 | 4-Bromo-benzo[g]isoquinoline 2-oxide (7-4) (380 mg, 1.39 mmol, 1 eq) was taken up in a ¼ v/v mixture of POCl3 and chloroform (20 ml) and the resulting solution was stirred at 55° C. for 2 hrs. The reaction mixture was then carefully poured into sat. aq. sodium bicarbonate, extracted with ethyl acetate, dried, and concentrated to give the crude desired chloride 7-5. LRMS m/z: found 294.0, 292.0, calcd. (M+H) 294.0, 292.0 | Clc1ncc(Br)c2cc3ccccc3cc12 | null | null | null |
896,874 | ord_dataset-de6bce51790e4004a27e1a8f2bcc7ded | null | 2009-01-01T00:08:00 | true | Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[C:4]([NH:12][C:13]2[CH:17]=[C:16]([CH3:18])[NH:15][N:14]=2)[N:3]=1.[CH2:19]([C:21]1[CH:22]=[C:23]([NH2:27])[CH:24]=[CH:25][CH:26]=1)[CH3:20]>>[CH2:19]([C:21]1[CH:22]=[C:23]([NH:27][C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[CH:5]=[C:4]([NH:12][C:13]3[CH:17]=[C:16]([CH3:18])[NH:15][N:14]=3)[N:3]=2)[CH:24]=[CH:25][CH:26]=1)[CH3:20] | Cc1cc(Nc2cc3ccccc3c(Cl)n2)n[nH]1 | CCc1cccc(N)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 | Similar procedure as described in example 273 was used, starting from (1-chloro-isoquinolin-3-yl)-(5-methyl-1H-pyrazol-3-yl)-amine and 3-ethyl-phenylamine give N1-(3-ethyl-phenyl)-N3-(5-methyl-1H-pyrazol-3-yl)-isoquinoline-1,3-diamine. LC-MS m/e 344(MH+). | CCc1cccc(Nc2nc(Nc3cc(C)[nH]n3)cc3ccccc23)c1 | null | null | null |
338,291 | ord_dataset-4706e7a7f3cd421bb42b7f877cff8af9 | null | 1996-01-01T00:09:00 | true | [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[N:9]=[C:10]=[S:11].[CH:12]([NH:15][CH2:16][C:17](O)=[O:18])([CH3:14])[CH3:13].C(N(CC)CC)C>C(Cl)(Cl)Cl>[CH3:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([CH3:1])[C:3]=1[N:9]1[C:17](=[O:18])[CH2:16][N:15]([CH:12]([CH3:14])[CH3:13])[C:10]1=[S:11] | CC(C)NCC(=O)O | Cc1cccc(C)c1N=C=S | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(CC)CC | ClC(Cl)Cl | null | null | null | null | null | null | null | null | null | null | null | The title compound was prepared by the procedure described in Example 45 using 16.3 g of 2,6-dimethylphenyl-isothiocyanate, 21.2 g of N-isopropyl glycine, 21.0 g of triethyl amine, and 300 mL of chloroform. Crystallization from ethanol afforded the title compound (12.9 g) as a white solid, m.p. 135°-137° C. Anal. Calcd. for. C14H18N2O S: C, 64.09; H, 6.92; N, 10.68. Found: C, 63.99; H, 6.72; N, 10.67. Mass spectrum (+FAB, I M+H]+) m/z 263. | Cc1cccc(C)c1N1C(=O)CN(C(C)C)C1=S | null | 49.2 | null |
838,177 | ord_dataset-074f86301ec5441ab3b52d902ac06949 | null | 2008-01-01T00:09:00 | true | [CH3:1][O:2][C:3]1[CH:12]=[C:11]([O:13][CH3:14])[CH:10]=[C:9]2[C:4]=1[C:5]([CH2:16][CH3:17])=[N:6][NH:7][C:8]2=O.P(Cl)(Cl)([Cl:20])=O>>[Cl:20][C:8]1[C:9]2[C:4](=[C:3]([O:2][CH3:1])[CH:12]=[C:11]([O:13][CH3:14])[CH:10]=2)[C:5]([CH2:16][CH3:17])=[N:6][N:7]=1 | CCc1n[nH]c(=O)c2cc(OC)cc(OC)c12 | O=P(Cl)(Cl)Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | This compound is obtained according to the procedure described in 1.3. by reacting 5,7-dimethoxy-4-ethyl-2H-phthalazin-1-one with phosphoryl chloride. | CCc1nnc(Cl)c2cc(OC)cc(OC)c12 | null | null | null |
1,280,776 | ord_dataset-d5c54236ecd94d61aaa071461bcfc426 | null | 2013-01-01T00:04:00 | true | Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=2)(=[O:10])=[O:9])=[C:4]([F:18])[CH:3]=1.[F:19][C:20]1[CH:21]=[CH:22][C:23]([O:29][CH3:30])=[C:24](B(O)O)[CH:25]=1>>[F:17][C:13]1[CH:12]=[C:11]([S:8]([C:5]2[CH:6]=[CH:7][C:2]([C:22]3[CH:21]=[C:20]([F:19])[CH:25]=[CH:24][C:23]=3[O:29][CH3:30])=[CH:3][C:4]=2[F:18])(=[O:10])=[O:9])[CH:16]=[CH:15][CH:14]=1 | O=S(=O)(c1cccc(F)c1)c1ccc(Br)cc1F | COc1ccc(F)cc1B(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 subtitle compound was prepared by the method of example 2 step (ii) using the product of step (ii) and 5-fluoro-2-methoxybenzene boronic acid. | COc1ccc(F)cc1-c1ccc(S(=O)(=O)c2cccc(F)c2)c(F)c1 | null | null | null |
179,348 | ord_dataset-4d84abdf99524e0fb6c42ab2a3300790 | null | 1988-01-01T00:10:00 | true | [NH:1]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:4](=[O:5])[C:2]1=[O:3].Cl.[CH:13]([N:16]([CH:21]([CH3:23])[CH3:22])[CH2:17][CH2:18][CH2:19]Cl)([CH3:15])[CH3:14]>>[CH:13]([N:16]([CH:21]([CH3:23])[CH3:22])[CH2:17][CH2:18][CH2:19][N:1]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:4](=[O:5])[C:2]1=[O:3])([CH3:15])[CH3:14] | CC(C)N(CCCCl)C(C)C | O=C1Nc2ccccc2C1=O | 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 | By using isatin and 3-diisopropylaminopropyl chloride hydrochloride, a method analogous to that described in Reference Example 1 was carried out, and the reaction product was purified with silica gel column chromatography (eluent: chloroform/methanol=50/1) and then recrystallized from hexane to obtain 1-(3-diisopropylaminopropyl)isatin having a melting point of 49°-50° C. (yield: 72.9%). | CC(C)N(CCCN1C(=O)C(=O)c2ccccc21)C(C)C | null | 72.9 | null |
1,624,164 | ord_dataset-35c51552812941cda45194a013d34bb9 | null | 2015-01-01T00:08:00 | true | [C:1]([C:3]1[C:4]2[S:13][C:12]([CH3:14])=[CH:11][C:5]=2[NH:6][C:7]=1C(O)=O)#[N:2].O>N1C2C(=CC=CC=2)C=CC=1.[Cu]>[C:1]([C:3]1[C:4]2[S:13][C:12]([CH3:14])=[CH:11][C:5]=2[NH:6][CH:7]=1)#[N:2] | Cc1cc2[nH]c(C(=O)O)c(C#N)c2s1 | null | null | [Cu] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | c1ccc2ncccc2c1 | null | null | null | null | null | null | null | null | null | 200 | 0.5 | To a solution of 6-cyano-2-methyl-4H-thieno[3,2-b]pyrrole-5-carboxylic acid (0.54 g) in quinoline (10 mL) was added Copper powder (33 mg), and the mixture was stirred at 200° C. for 30 minutes using microwave reactor. To the reaction solution was added water, and a precipitated insoluble matter was filtered through a Celite pad (registered trademark). The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with 1 mol/L hydrochloric acid, water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=76/24−53/47) to give the title compound (0.37 g). | Cc1cc2[nH]cc(C#N)c2s1 | null | 87.1 | null |
179,121 | ord_dataset-4d84abdf99524e0fb6c42ab2a3300790 | null | 1988-01-01T00:10:00 | true | [CH3:1][C:2]1[N:7]=[CH:6][C:5]([CH:8]=[CH:9][C:10]([OH:12])=O)=[CH:4][CH:3]=1.C(Cl)(=O)C(C)(C)C.[C:20]1([CH:26]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[N:27]2[CH2:32][CH2:31][N:30]([CH2:33][CH2:34][CH2:35][CH2:36][NH2:37])[CH2:29][CH2:28]2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.C(N(CC)CC)C>[CH3:1][C:2]1[N:7]=[CH:6][C:5]([CH:8]=[CH:9][C:10]([NH:37][CH2:36][CH2:35][CH2:34][CH2:33][N:30]2[CH2:31][CH2:32][N:27]([CH:26]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH2:28][CH2:29]2)=[O:12])=[CH:4][CH:3]=1 | Cc1ccc(C=CC(=O)O)cn1 | NCCCCN1CCN(C(c2ccccc2)c2ccccc2)CC1 | null | CC(C)(C)C(=O)Cl | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | CCN(CC)CC | null | null | null | null | null | null | null | null | null | -5 | 0.5 | To a suspension of 2.71 g of 3-(6-methyl-3-pyridyl)acrylic acid in 70 ml of dry tetrahydrofuran, a solution of 1.68 g of triethylamine in 5 ml of dry tetrahydrofuran is added at room temperature. The resulting solution is cooled to -5° C., and a solution of 2.0 g of pivaloyl chloride in 5 ml of dry tetrahydrofuran is added slowly. The mixture is stirred at the same temperature for 0.5 hour and cooled to -10° C., and a solution of 6.43 g of 4-(4-diphenylmethyl-1-piperazinyl)butylamine in 5 ml of dry tetrahydrofuran is added slowly. The mixture is stirred for 0.5 hour at between -10° C. and -5° C. and then at room temperature overnight. To the reaction mixture is added 50 ml of 10% aqueous potassium carbonate, and the resulting mixture is extracted with three 100-ml portions of ethyl acetate. The combined extracts are washed with water and dried over magnesium sulfate, and the solvent is distilled off. The residue is recrystallized from acetonitrile to give 5.63 g of the title compound, m.p. 129°-131° C. | Cc1ccc(C=CC(=O)NCCCCN2CCN(C(c3ccccc3)c3ccccc3)CC2)cn1 | null | 72.3 | null |
1,410,718 | ord_dataset-7456bda2326f4bebaa874a5474d4cc0d | null | 2014-01-01T00:03:00 | true | C([O:3][C:4](=[O:23])[CH:5]([C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=1)[CH2:6][CH2:7][NH:8][C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])C.O.[OH-].[Li+]>C1COCC1.O>[C:12]([O:11][C:9]([NH:8][CH2:7][CH2:6][CH:5]([C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=1)[C:4]([OH:23])=[O:3])=[O:10])([CH3:15])([CH3:13])[CH3:14] | CCOC(=O)C(CCNC(=O)OC(C)(C)C)c1ccc(Cl)cc1 | null | null | [Li+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | O | null | null | null | null | null | null | null | null | null | null | null | The 4-tert-butoxycarbonylamino-2-(4-chlorophenyl)-butyric acid ethyl ester (5.61 g, 16.4 mmol) was dissolved in 40 mL of THF and 10 mL of water, then cooled to 0° C. The mixture was treated with lithium hydroxide mono-hydrate (1.38 g, 32.8 mmol) to afford a yellow solution. The ice-bath was removed, and the mixture was allowed to stir overnight to room temperature. The reaction mixture was concentrated to approximately 15 mL and diluted with water. The aqueous was washed with ethyl acetate (discarded) then treated with 3M HCl solution until acidic (pH=2-3). The resulting white precipitate was extracted with ethyl acetate, and the organics were combined. The organic was washed with brine, separated, dried over MgSO4, filtered, and concentrated in vacuo to afford the 4-tert-butoxycarbonylamino-2-(4-chlorophenyl)-butyric acid as a colorless oil. The material was re-dissolved in a minimal amount of warm (60° C.) hexanes and re-concentrated to afford the pure desired product as a white foam. 1H NMR (CDCl3, 400 MHz) δ 12.05-9.51 (brs, 1H), 7.31-7.25 (m, 4H), 4.59 (brs, 1H), 3.61 (d, J=7.6 Hz, 1H), 3.14 (brs, 2H), 2.28 (m, 1H), 1.92 (m, 1H), 1.43 (s, 9H). | CC(C)(C)OC(=O)NCCC(C(=O)O)c1ccc(Cl)cc1 | null | null | null |
1,755,091 | ord_dataset-97eb2ab57fec4160922caae33b54d956 | null | 2016-01-01T00:08:00 | true | [OH:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[CH:9][CH:10]=2)[CH:5]=[N:4][C:3]=1[C:19]([NH:21][CH2:22][CH2:23][CH2:24][C:25]([OH:27])=[O:26])=[O:20].S(=O)(=O)(O)O.[CH3:33]O>>[CH3:33][O:26][C:25](=[O:27])[CH2:24][CH2:23][CH2:22][NH:21][C:19]([C:3]1[N:4]=[CH:5][C:6]2[C:11]([C:2]=1[OH:1])=[CH:10][CH:9]=[C:8]([O:12][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)[CH:7]=2)=[O:20] | O=C(O)CCCNC(=O)c1ncc2cc(Oc3ccccc3)ccc2c1O | CO | null | O=S(=O)(O)O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | 25 | null | To a solution of 4-[(4-hydroxy-7-phenoxy-isoquinoline-3-carbonyl)-amino]-butyric acid (1.32 g, 3.6 mmol) in MeOH (7.2 mL) was added 10% sulfuric acid. The reaction mixture was stirred at reflux for 20 hours. After cooled to rt, the solvent was concentrated in vacuo as a oil and purified by silica gel chromatography over silica gel, eluting with 15-75% EtOAc/hexanes to give product (900 mg) as a colorless oil: MS (m/z) 381.0 (M+1)+. | COC(=O)CCCNC(=O)c1ncc2cc(Oc3ccccc3)ccc2c1O | null | null | null |
1,511,028 | ord_dataset-1a1aa5d1c3224edca0aec6e3398da985 | null | 2014-01-01T00:11:00 | true | C([O:3][C:4](=[O:23])[CH2:5][CH2:6][CH2:7][O:8][C:9]1[C:14]2[B:15]([OH:22])[O:16][CH:17]([CH2:18][N+:19]([O-:21])=[O:20])[C:13]=2[CH:12]=[CH:11][CH:10]=1)C.[OH-].[Na+]>CO.O>[OH:22][B:15]1[C:14]2[C:9]([O:8][CH2:7][CH2:6][CH2:5][C:4]([OH:23])=[O:3])=[CH:10][CH:11]=[CH:12][C:13]=2[CH:17]([CH2:18][N+:19]([O-:21])=[O:20])[O:16]1 | CCOC(=O)CCCOc1cccc2c1B(O)OC2C[N+](=O)[O-] | null | null | [Na+] | [OH-] | 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 | 25 | 5 | A mixture of 4-(1-hydroxy-3-nitromethyl-1,3-dihydro-benzo[c][1,2]oxaborol-7-yloxy)-butyric acid ethyl ester (2.51 g, 7.78 mmol), 10% NaOH (17 mL), and 1:1 MeOH/H2O (70 mL) was stirred at rt for 5 h. The MeOH was removed in vacuo and the remaining aqueous layer was acidified to pH 1 using 2 M HCl. The aqueous layer was then extracted with EtOAc. The organic fractions were washed with brine, dried (MgSO4), and concentrated in vacuo to give the title compound as a pale yellow foam: yield 1.85 g (81%). | O=C(O)CCCOc1cccc2c1B(O)OC2C[N+](=O)[O-] | null | null | null |
1,140,821 | ord_dataset-68715347640045adb1b09e6a04722b0e | null | 2012-01-01T00:03:00 | true | [Br-].[CH2:2]([O:9]CCC[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[C:3]1C=CC=C[CH:4]=1.[H-].[Na+].[CH2:34]1[CH2:44][C:42](=O)[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH2:35]1.O>O1CCCC1>[OH:9][CH2:2][CH2:3][CH2:4][CH:42]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH2:35][CH2:34][CH2:44]1 | c1ccc(COCCC[P+](c2ccccc2)(c2ccccc2)c2ccccc2)cc1 | O=C1CCCc2ccccc21 | null | [Br-] | [H-] | [Na+] | 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 | 1 | (3-Benzyloxypropyl)triphenylphosphoniumbromide (1.00 g) was dissolved in tetrahydrofuran (10 ml), sodium hydride (162 mg) was added under ice-cooling, and the mixture was stirred at room temperature for 1 hr. α-Tetralone (1.36 ml) was added to the reaction mixture, and the mixture was stirred at 75° C. for 48 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. To a solution of the obtained residue in ethyl acetate (10 ml) was added 10% palladium carbon (200 mg), and the mixture was stirred under a hydrogen atmosphere at room temperature for 18 hr. The reaction container was purged with nitrogen, the solution was filtered, and the filtrate was concentrated. The obtained residue was purified by silica gel column chromatography to give the object product (140 mg) as a colorless oil. | OCCCC1CCCc2ccccc21 | null | null | null |
680,232 | ord_dataset-3947f3e1be17462c8f7c7e6ea6e57d0a | null | 2005-01-01T00:08:00 | true | [CH2:1]([NH:9][C:10]([C:12]1[CH:13]=[C:14]([C:18]2[CH:23]=[CH:22][C:21]([CH:24]=[C:25]3[S:29][C:28](=[O:30])[NH:27][C:26]3=[O:31])=[CH:20][CH:19]=2)[CH:15]=[CH:16][CH:17]=1)=[O:11])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]>[Pd].CN(C)C=O>[CH2:1]([NH:9][C:10]([C:12]1[CH:13]=[C:14]([C:18]2[CH:19]=[CH:20][C:21]([CH2:24][CH:25]3[S:29][C:28](=[O:30])[NH:27][C:26]3=[O:31])=[CH:22][CH:23]=2)[CH:15]=[CH:16][CH:17]=1)=[O:11])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8] | CCCCCCCCNC(=O)c1cccc(-c2ccc(C=C3SC(=O)NC3=O)cc2)c1 | null | null | [Pd] | 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 | 80 | 5 | 150 mg (0.35 mmol) of N-octyl-4′-(2,4-dioxo-thiazolidin-5-ylidenemethyl)biphenyl-3-carboxamide, 20 ml of dimethylformamide and 150 mg of palladium-on-charcoal (10%) are introduced into a reactor under a stream of nitrogen. The medium is heated at 80° C. and hydrogenated under a pressure of 3 atm for 5 hours. The reaction medium is filtered through Celite. The filtrate is placed in water, extracted with ethyl acetate and washed thoroughly with water. The organic phase is dried over magnesium sulfate, filtered and evaporated. The residue is chromatographed on a column of silica, eluted with a mixture of heptane and ethyl acetate (30/70). 100 mg (65%) of the expected product, with a melting point of 137-138° C., are obtained. | CCCCCCCCNC(=O)c1cccc(-c2ccc(CC3SC(=O)NC3=O)cc2)c1 | null | 65.1 | null |
1,163,169 | ord_dataset-d24cc23b3db94284bb83a2ccdd9eb880 | null | 2012-01-01T00:05:00 | true | [CH2:1]([C:3]1[C:8](=[O:9])[NH:7][C:6]([CH3:10])=[C:5]([C:11]2[S:15][C:14]([S:16](Cl)(=[O:18])=[O:17])=[CH:13][CH:12]=2)[CH:4]=1)[CH3:2].[OH:20][CH:21]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH2:22][NH:23][CH3:24]>>[OH:20][CH:21]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH2:22][N:23]([CH3:24])[S:16]([C:14]1[S:15][C:11]([C:5]2[CH:4]=[C:3]([CH2:1][CH3:2])[C:8](=[O:9])[NH:7][C:6]=2[CH3:10])=[CH:12][CH:13]=1)(=[O:18])=[O:17] | CNCC(O)c1ccccc1 | CCc1cc(-c2ccc(S(=O)(=O)Cl)s2)c(C)[nH]c1=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 | 5-(5-Ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-sulfonyl chloride is reacted with (2-hydroxy-2-phenylethyl)methylamine as described in Step 5, Example 24 to give the title compound as a solid (58% yield). LC/MS: RT 2.93 min; m/e 433 (M+H); 1H NMR (δ, ppm): 11.81 (1H, s), 7.59 (1H, d), 7.34 (6H, m); 7.19 (1H, d), 5.61 (1H, d), 4.78 (1H, q), 3.12 (2H), 2.78 (3H, s), 2.38 (2H), 2.31 (3H, s), 1.09 (3H, t). | CCc1cc(-c2ccc(S(=O)(=O)N(C)CC(O)c3ccccc3)s2)c(C)[nH]c1=O | null | 58 | null |
1,655,507 | ord_dataset-42cd9bc5aae3485f9a58f1527bd3abf0 | null | 2015-01-01T00:11:00 | true | O1[CH:5]=[N:4][N:3]=[C:2]1[C:6]1[CH:14]=[CH:13][C:9]2[N:10]=[CH:11][NH:12][C:8]=2[CH:7]=1.[F:15][C:16]1[CH:17]=[C:18]([CH:21]=[CH:22][C:23]=1[F:24])[CH2:19][NH2:20]>>[F:15][C:16]1[CH:17]=[C:18]([CH:21]=[CH:22][C:23]=1[F:24])[CH2:19][N:20]1[CH:5]=[N:4][N:3]=[C:2]1[C:6]1[CH:14]=[CH:13][C:9]2[NH:10][CH:11]=[N:12][C:8]=2[CH:7]=1 | c1nc2ccc(-c3nnco3)cc2[nH]1 | NCc1ccc(F)c(F)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The compound was synthesized starting from 5-(1,3,4-oxadiazol-2-yl)benzimidazole (186 mg, 1 mmol) and 3,4-difluorobenzylamine (0.5 ml) as described above; yield: 0.049 g (15.8%); MS m/z: 312.2 [M+H]+; 1H-NMR (DMSO d6, 400 MHz): δ 5.36 (s, 2H); 6.81-6.84 (m, 1H); 7.13-7.19 (m, 1H); 7.29-7.36 (m, 1H); 7.59 (dd, 1H, 4J=1.7 Hz, 3J=8.7 Hz); 7.82 (d, 1H, 3J=8.7 Hz); 7.88 (d, 1H, 4J=1.7 Hz); 8.77 (s, 1H); 9.03 (s, 1H); HPLC (METHOD [A]): it 8.82 min (95.6%) | Fc1ccc(Cn2cnnc2-c2ccc3[nH]cnc3c2)cc1F | null | null | null |
1,479,815 | ord_dataset-c3c1091f873b4f40827973a6f1f9b685 | null | 2014-01-01T00:09:00 | true | [CH2:1]1[C:10]2[CH:5]([CH2:6][CH2:7][CH2:8][CH:9]=2)[CH2:4][CH2:3][O:2]1.C1C=C(Cl)C=C(C(OO)=[O:19])C=1>C(Cl)Cl>[O:19]1[C@@:10]23[C@H:5]([CH2:4][CH2:3][O:2][CH2:1]2)[CH2:6][CH2:7][CH2:8][CH:9]13 | O=C(OO)c1cccc(Cl)c1 | C1=C2COCCC2CCC1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | 25 | 3 | To a mixture of 3,4,4a,5,6,7-hexahydro-1H-isochromene (0.410 g, 2.97 mmol) in CH2Cl2 (10 mL) at 0° C. was added MCPBA (˜77%, 1.24 g, 445 mmol). The mixture was stirred at rt for 3 hr. It was quenched with sat'd aq. sodium sulfite. The mixture was diluted with CH2Cl2 and sat'd. aq. NaHCO3 then extracted 3× with CH2Cl2. The combined organics were dried (anhd. Na2SO4), filtered, and concentrated. The residue was purified by column chromatography to give the title compound. 1H NMR (500 MHz, CDCl3) δ 4.03-4.10 (m, 1H), 3.86 (d, 1H, J=12.0 Hz), 3.54-3.62 (m, 1H), 3.34 (d, 1H, J=12.0 Hz), 3.03 (d, 1H, J=4.4 Hz), 1.70-1.98 (m, 3H), 1.52-1.65 (m, 3H), 1.17-1.34 (m, 3H). | C1CC2O[C@@]23COCC[C@@H]3C1 | null | null | null |
1,438,414 | ord_dataset-275a3da8f45f4536ad29727f0ef9ba66 | null | 2014-01-01T00:06:00 | true | [CH:1]1[CH:2]=[CH:3][N:4]=[C:5]([C:7]2[CH:8]=[CH:9][C:10]([C:13]([NH:15][CH2:16]/[CH:17]=[CH:18]/[CH2:19][N:20]3[CH2:25][CH2:24][N:23]([C:26]4[C:31]([Cl:32])=[C:30]([Cl:33])[CH:29]=[CH:28][CH:27]=4)[CH2:22][CH2:21]3)=[O:14])=[CH:11][CH:12]=2)[CH:6]=1.ClC1C=CC=C(C(OO)=[O:42])C=1>ClCCl>[Cl:32][C:31]1[C:30]([Cl:33])=[CH:29][CH:28]=[CH:27][C:26]=1[N:23]1[CH2:24][CH2:25][N+:20]([O-:42])([CH2:19]/[CH:18]=[CH:17]/[CH2:16][NH:15][C:13](=[O:14])[C:10]2[CH:11]=[CH:12][C:7]([C:5]3[CH:6]=[CH:1][CH:2]=[CH:3][N:4]=3)=[CH:8][CH:9]=2)[CH2:21][CH2:22]1 | O=C(OO)c1cccc(Cl)c1 | O=C(NC/C=C/CN1CCN(c2cccc(Cl)c2Cl)CC1)c1ccc(-c2ccccn2)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | 25 | 16 | A solution of PG01037, see U.S. 2006/0106030 (288 mg, 0.60 mmol) in 10 mL dichloromethane was treated at 0° C. with meta-chloroperbenzoic acid (0.16 g, 77%, 0.72 mmol). After stirring for 16 h at room temperature, the reaction mixture was successively washed with saturated sodium bicarbonate solution, H2O and brine and dried with sodium sulphate. The volatiles were removed in vacuo and the residue was purified by preparative thin layer chromatography. Yield: 93 mg (32%). Mp. (hydrochloride): foam. 1H NMR (CD3OD): δ 3.23-3.29 (m, 4H), 3.50-3.61 (m, 4H), 3.99 (d, J 6.5, 1H), 4.13 (d, J 4.6, 1H), 6.04-6.18 (m, 2H), 7.18 (dd, J 7.8, 3.9, 1H), 7.24-7.28 (m, 2H), 7.40 (m, 1H), 7.91-7.93 (m, 2H), 7.99 (d, J 8.4, 2H), 8.06 (d, J 8.7, 2H), 8.64 (dt, J 4.8, 1.2, 1H). 13C NMR (CDCl3): δ 41.0, 45.5, 63.5, 72.0, 119.3, 120.0, 121.6, 123.1, 125.4, 127.0, 127.3, 127.7, 128.0, 133.8, 134.6, 137.8, 137.9, 142.2, 149.3, 150.1, 156.4, 168.3. Anal. (C26H26Cl2N4O2:2HCl.0.5H2O) C, H, N. | O=C(NC/C=C/C[N+]1([O-])CCN(c2cccc(Cl)c2Cl)CC1)c1ccc(-c2ccccn2)cc1 | null | null | null |
963,546 | ord_dataset-ed65749688da45af8a8432967b017729 | null | 2010-01-01T00:05:00 | true | [CH:1]1([N:7]([CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)[C:8](Cl)=[S:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[OH:17][N:18]1[C:22](=[O:23])[C:21]2=[CH:24][CH:25]=[CH:26][CH:27]=[C:20]2[C:19]1=[O:28]>>[O:28]=[C:19]1[C:20]2[C:21](=[CH:24][CH:25]=[CH:26][CH:27]=2)[C:22](=[O:23])[N:18]1[O:17][C:8](=[S:9])[N:7]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)[CH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1 | S=C(Cl)N(C1CCCCC1)C1CCCCC1 | O=C1c2ccccc2C(=O)N1O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | This compound was prepared in analogy to example 8 starting from 24.94 g (0.096 mol) of dicyclohexyl-thiocarbamoyl chloride (prepared as described in (Chem. Ber., 101, (1968), 113) and N-hydroxyphthalimide. Yield 9.65 g of white crystals after recrystallization from hexane, mp. 148-150° C. | O=C1c2ccccc2C(=O)N1OC(=S)N(C1CCCCC1)C1CCCCC1 | null | null | null |
728,998 | ord_dataset-eb4226b4f7644a01a737e7547b70014a | null | 2006-01-01T00:09:00 | true | [CH3:1][O:2][C:3]1[C:8]([O:9][CH3:10])=[CH:7][C:6]([C:11]2[O:12][C:13]3[CH:19]=[CH:18][CH:17]=[C:16]([CH2:20][NH:21][CH2:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=4)[C:14]=3[N:15]=2)=[C:5]([O:29]COC)[CH:4]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[CH3:1][O:2][C:3]1[C:8]([O:9][CH3:10])=[CH:7][C:6]([C:11]2[O:12][C:13]3[CH:19]=[CH:18][CH:17]=[C:16]([CH2:20][NH:21][CH2:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=4)[C:14]=3[N:15]=2)=[C:5]([OH:29])[CH:4]=1 | COCOc1cc(OC)c(OC)cc1-c1nc2c(CNCc3ccccn3)cccc2o1 | null | null | Cc1ccc(S(=O)(=O)O)cc1 | null | 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 | 25 | 8 | A mixture of 7 (100 mg, 0.23 mmol) and p-toluenesulfonic acid monohydrate (190 mg, 1 mmol) in methanol (20 mL) was stirred overnight at room temperature. After the solvent was evaporated, ethyl acetate (20 mL) was added to the resulting residue which was neutralized by Na2CO3, washed with brine and water, dried over MgSO4, and concentrated in vacuo to give a pale yellow solid that was purified by silica gel column chromatography (ethyl acetate) and crystallized from ethanol to afford a white solid of Zinbo-5 (80 mg, 89%): 1H-NMR (500 MHz, CDCl3) δ3.95 (s, 3H), 3.96 (s, 3H), 4.01 (s, 2H), 4.21 (s, 2H), 6.66 (s, 1H), 7.17 (dd, 1H, J=7.5, 5.0 Hz), 7.31 (t, 1H, J=8.0 Hz), 7.37–7.40 (m, 2H), 7.41 (s, 1H), 7.48 (d, 1H, J=8.0 Hz),7.67 (t, 1H, J=7.5 Hz), 8.66 (d, 2H, J=5.0 Hz), 11.27 (s, 1H); Anal. Calcd for C22H21N3O4: C, 67.51; H, 5.41; N, 10.74. Found: C, 67.12; H, 5.25; N, 10.57. | COc1cc(O)c(-c2nc3c(CNCc4ccccn4)cccc3o2)cc1OC | null | 88.9 | null |
410,090 | ord_dataset-fbdd058349aa456f812e3546c84baab5 | null | 1998-01-01T00:09:00 | true | [F:1][C:2]1[CH:3]=[CH:4][C:5]2[C:9]([N:10]3[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][CH2:18][CH2:19][NH2:20])[CH2:12][CH2:11]3)=[CH:8][S:7][C:6]=2[CH:21]=1.C(N(CC)CC)C.[F:29][C:30]1[CH:38]=[CH:37][C:33]([C:34](Cl)=[O:35])=[CH:32][CH:31]=1>ClCCl>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[C:9]([N:10]3[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][CH2:18][CH2:19][NH:20][C:34](=[O:35])[C:33]4[CH:37]=[CH:38][C:30]([F:29])=[CH:31][CH:32]=4)[CH2:12][CH2:11]3)=[CH:8][S:7][C:6]=2[CH:21]=1 | NCCCCN1CCN(c2csc3cc(F)ccc23)CC1 | O=C(Cl)c1ccc(F)cc1 | 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 | 0 | 1.17 | To a 0° C. solution of 4-(6-fluorobenzo[b]thien-3-yl)-1-piperazine-butanamine (2.45 g, 7.97 mmol), triethylamine (1.23 g, 12.2 mmol), and dichloromethane (30 mL) under a nitrogen atmosphere was added 4-fluorobenzoyl chloride (1.61 g, 10.2 mmol) in one portion. The reaction was stirred at 0° C. for 70 minutes and then at room temperature for 3 hours. The reaction was diluted with dichloromethane (50 mL) and the mixture was washed successively with 5% aqueous NaOH (50 mL) and water (50 mL), dried (Na2SO4), and concentrated in vacuo to a tan solid. The crude product was chromatographed on silica gel with 10% ethanol/dichloromethane as eluent to afford an 2.22 g of an off-white solid. Recrystallization from ethyl acetate/heptane gave 1.60 g (46%) of the title compound as beige needles, m.p. 161°-163° C. | O=C(NCCCCN1CCN(c2csc3cc(F)ccc23)CC1)c1ccc(F)cc1 | null | 64.8 | null |
785,770 | ord_dataset-4ad5db8537994579bef51f16dd8bf0bd | null | 2007-01-01T00:08:00 | true | [Cl:1][C:2]1[C:3]2[CH:11]=[CH:10][NH:9][C:4]=2[N:5]=[C:6]([CH3:8])[N:7]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:18]([O:20][C:21](=[O:26])[CH2:22][CH2:23][CH2:24]Br)[CH3:19]>CN(C=O)C>[CH2:18]([O:20][C:21](=[O:26])[CH2:22][CH2:23][CH2:24][N:9]1[C:4]2[N:5]=[C:6]([CH3:8])[N:7]=[C:2]([Cl:1])[C:3]=2[CH:11]=[CH:10]1)[CH3:19] | Cc1nc(Cl)c2cc[nH]c2n1 | CCOC(=O)CCCBr | null | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | 50 | 0.75 | 0.5 g (3 mmol) of 4-chloro-2-methyl-7H-pyrrolo[2,3-d]pyrimidine (prepared according to West and Beauchamp, J. Org. Chem. 26 (1961) 3809) was dissolved in 3 ml DMF and 2.06 g (15 mmol) of potassium carbonate was added to this solution. 0.431 ml (3 mmol) of 4-bromobutyric acid ethyl ester was added and the mixture was stirred at 50° C. for 45 minutes. The reaction mixture was diluted with 50 ml EE and washed three times with water, dried over MgSO4, filtered and the solvent was removed in vacuo. Yield: 0.8 g. | CCOC(=O)CCCn1ccc2c(Cl)nc(C)nc21 | null | null | null |
1,015,506 | ord_dataset-f024e9664ab64906a71a2ff6004cb3d0 | null | 2010-01-01T00:12:00 | true | [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[N:10]=[C:9]([N:11]2[CH2:16][CH2:15][N:14](C(OC(C)(C)C)=O)[CH2:13][CH2:12]2)[S:8][N:7]=1.Cl.CCCCCC>C(OCC)(=O)C>[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[N:10]=[C:9]([N:11]2[CH2:12][CH2:13][NH:14][CH2:15][CH2:16]2)[S:8][N:7]=1 | CC(C)(C)OC(=O)N1CCN(c2nc(-c3cccs3)ns2)CC1 | null | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCCCCC | CCOC(C)=O | null | null | null | null | null | null | null | null | null | 25 | 18 | To a solution of tert-butyl 4-[3-(2-thienyl)-1,2,4-thiadiazol-5-yl]piperazine-1-carboxylate (4.30 g, 12.2 mmol) in ethyl acetate (70 ml) was added a solution of 4 N hydrochloric acid in ethyl acetate (35 ml), and the mixture was stirred at room temperature for 18 hours and half. Hexane (150 ml) was poured to the reaction mixture, and a solid was separated by filtration. The obtained solid was dissolved in an aqueous saturated sodium hydrogen carbonate solution, followed by stirring at room temperature for 2 hours. Water was poured to the reaction mixture, and the resulting solution was extracted with a mixed solution of ethyl acetate/tetrahydrofuran (1:1). The extract was washed with water and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. Hexane was poured to the residue, and 2.31 g (75.0%) of the desired product as a solid was separated by filtration. | c1csc(-c2nsc(N3CCNCC3)n2)c1 | null | null | null |
1,320,080 | ord_dataset-2d6edb8ffd434003bb508360153bd9bb | null | 2013-01-01T00:07:00 | true | C([O:8][C:9]1[CH:33]=[CH:32][C:31]([CH:34]2[CH2:39][CH2:38][N:37]([CH2:40][CH2:41][OH:42])[CH2:36][CH2:35]2)=[CH:30][C:10]=1[C:11]([NH:13][C:14]1[CH:23]=[C:22]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:21]=[CH:20][C:15]=1[C:16]([O:18][CH3:19])=[O:17])=[O:12])C1C=CC=CC=1>C(OCC)(=O)C.CO.[C].[Pd]>[OH:8][C:9]1[CH:33]=[CH:32][C:31]([CH:34]2[CH2:35][CH2:36][N:37]([CH2:40][CH2:41][OH:42])[CH2:38][CH2:39]2)=[CH:30][C:10]=1[C:11]([NH:13][C:14]1[CH:23]=[C:22]([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:21]=[CH:20][C:15]=1[C:16]([O:18][CH3:19])=[O:17])=[O:12] | COC(=O)c1ccc(-c2ccccc2)cc1NC(=O)c1cc(C2CCN(CCO)CC2)ccc1OCc1ccccc1 | null | null | [Pd] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | CCOC(C)=O | null | null | null | null | null | null | null | null | null | 25 | 2 | To a solution mixture of the obtained methyl 2-(2-(benzyloxy)-5-(1-(2-hydroxyethyl)piperidin-4-yl)benzamido)-4-phenylbenzoate (0.085 g) in ethyl acetate (1.0 mL) and methanol (1.0 mL), 10% palladium-carbon (0.040 g) was added, followed by stirring under a hydrogen atmosphere at room temperature for 2 hours. To the reaction mixture, 10% palladium-carbon (0.040 g) was added, followed by stirring under a hydrogen atmosphere at room temperature for 4 hours. The insoluble substance was removed from the reaction mixture by filtration, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography [eluent: 100-92% chloroform/methanol] to obtain 0.035 g of methyl 2-(2-hydroxy-5-(1-(2-hydroxyethyl)piperidin-4-yl)benzamido)-4-phenylbenzoate as a white solid. | COC(=O)c1ccc(-c2ccccc2)cc1NC(=O)c1cc(C2CCN(CCO)CC2)ccc1O | null | 49 | null |
269,138 | ord_dataset-a20aed058d7b40bc81fdf50bc5b03f97 | null | 1993-01-01T00:06:00 | true | [N+:1]([C:4]1[CH:11]=[CH:10][CH:9]=[CH:8][C:5]=1[CH:6]=O)([O-:3])=[O:2].[NH3:12]>CO>[N+:1]([C:4]1[CH:11]=[CH:10][CH:9]=[CH:8][C:5]=1[CH:6]=[NH:12])([O-:3])=[O:2] | O=Cc1ccccc1[N+](=O)[O-] | N | 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 | To a solution of 15.1 g (0.1 mole) of 2-nitrobenzaldehyde and 40 ml of methanol a methanolic solution of 1.7 g (0.1 mole) of ammonia is added dropwise under stirring. The reaction mixture is stirred at room temperature for 20 hours, then cooled, the precipitated product is filtered, washed with methanol and dried. Thus 11.3 g of trimeric 2-nitro-benzaldehyde-imine are obtained, yield 75.3%, m. p.: 117°-119° C. | N=Cc1ccccc1[N+](=O)[O-] | null | 75.3 | null |
1,120,454 | ord_dataset-4226e9b4f9f845db967ed997270dcafc | null | 2011-01-01T00:12:00 | true | [Br:1][C:2]1[C:3]([CH3:18])=[C:4]([C:8]#[C:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH2:16][OH:17])[CH:5]=[CH:6][CH:7]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1.CCOC(C)=O>[Br:1][C:2]1[C:3]([CH3:18])=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH:8]=[C:9]1[C:10]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH2:16][O:17]1 | Cc1c(Br)cccc1C#Cc1ccccc1CO | null | null | CCCC[N+](CCCC)(CCCC)CCCC | [F-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | CCOC(C)=O | null | null | null | null | null | null | null | null | null | null | null | Step 2 A solution of (2-((3-bromo-2-methylphenyl)ethynyl)phenyl)-methanol (50 mg, 0.166 mmol) and tetrabutylammonium fluoride, 1.0 M in THF (0.332 mL, 0.332 mmol) in THF (0.5 mL) was heated at 67° C. for 2 h. The mixture was diluted with EtOAc, washed twice with water and once with brine, dried and concentrated. The residue was purified by column chromatography (eluting with a gradient from hexane to 80:20 EtOAc-hexane) to provide 1-(3-bromo-2-methylbenzylidene)-1,3-dihydroisobenzofuran as a light yellow solid (36 mg, 72%). 1H NMR (400 MHz, chloroform-d) δ 8.00-8.06 (1H, m), 7.58-7.64 (1H, m), 7.32-7.41 (4H, m), 7.04 (1H, t, J=7.92 Hz), 6.07 (1H, s), 5.49 (2H, s), 2.51 (3H, s). Mass spectrum m/z 301, 303 (M+H)+. | Cc1c(Br)cccc1C=C1OCc2ccccc21 | null | 72 | null |
278,010 | ord_dataset-ad17798fcea64e26ba91604fca520090 | null | 1993-01-01T00:10:00 | true | [Br:1][C:2]1[CH:3]=[C:4]([CH3:9])[CH:5]=[C:6]([Br:8])[CH:7]=1.[Br:10]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl.CCCCCC.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>[Br:1][C:2]1[CH:3]=[C:4]([CH:5]=[C:6]([Br:8])[CH:7]=1)[CH2:9][Br:10] | O=C1CCC(=O)N1Br | Cc1cc(Br)cc(Br)c1 | null | O=C(OOC(=O)c1ccccc1)c1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCCCCC | ClC(Cl)(Cl)Cl | null | null | null | null | null | null | null | null | null | 25 | null | 3,5-dibromotoluene (78.92 g, 0.316 mole) was dissolved in 1.27 L of carbon tetrachloride; to this solution was added N-bromosuccinimide (61.65 g, 0.346 mole) at room temperature. A portion of dibenzoyl peroxide (0.6 g, 0.008 equivalents) was added and the solution heated to reflux temperature for 2.5 hours. The reaction mixture was cooled to room temperature, filtered and the solvent removed in vacuo to yield a solid. The solid was dissolved in 200 mL of warm hexane, filtered and cooled to room temperature. Crystallizations ensued; the crystals were filtered off and washed with cold hexane and air dried to give 45.15 g (44%) of 3,5-dibromobenzyl bromide. 1H-NMR(CDCl3); δ 7.6 (1H), 7.47 (2H), 4.36 (2H). | BrCc1cc(Br)cc(Br)c1 | null | 43.5 | null |
1,568,230 | ord_dataset-9741bb5fd93044078df2a45f45733054 | null | 2015-01-01T00:04:00 | true | Cl.Cl.[Br:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]([CH2:14][CH3:15])[CH2:11][CH2:12][NH2:13])=[CH:6][CH:5]=1.N1C=CC=CC=1.[C:22](OC(=O)C)(=[O:24])[CH3:23]>ClCCl>[Br:3][C:4]1[CH:5]=[CH:6][C:7]([N:10]([CH2:14][CH3:15])[CH2:11][CH2:12][NH:13][C:22](=[O:24])[CH3:23])=[CH:8][CH:9]=1 | CC(=O)OC(C)=O | CCN(CCN)c1ccc(Br)cc1 | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | c1ccncc1 | ClCCl | null | null | null | null | null | null | null | null | null | 25 | 1.17 | To a mixture of N-(4-bromophenyl)-N-ethylethane-1,2-diamine dihydrochloride (1.044 g, corresponding to 2.33 mmol), pyridine (4 ml) and anhydrous dichloromethane (8 ml) was added dropwise acetic anhydride (0.28 ml, 2.92 mmol) at 0° C. After stirring at room temperature for 70 mins, the reaction mixture was diluted with dichloromethane (50 ml), washed twice with diluted aqueous sodium hydrogen carbonate solution and with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:4→1:0) to give N-{2-[(4-bromophenyl)(ethyl)amino]ethyl}acetamide (460 mg, overall yield of 2 steps 92%) as a white solid. | CCN(CCNC(C)=O)c1ccc(Br)cc1 | null | 69.2 | null |
1,181,225 | ord_dataset-0f9d2dbe929a45c3892ae75e81e99443 | null | 2012-01-01T00:06:00 | true | [S:1]1[CH2:6][CH2:5][CH2:4][S:3][CH2:2]1.[Li]CCCC.[CH3:12][O:13][CH2:14][CH2:15]Br>C1COCC1>[CH3:12][O:13][CH2:14][CH2:15][CH:2]1[S:3][CH2:4][CH2:5][CH2:6][S:1]1 | COCCBr | C1CSCSC1 | null | [Li]CCCC | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | -78 | null | A solution of 1,3-dithiane (15.12 g, 126.0 mmol) in dry THF (150 mL) was treated at 0° C. with BuLi (53.0 mL of a 2.5 M solution, 132.5 mmol, 1.05 eqiuv) for 1.5 h. The reaction mixture was cooled to −78° C., and 2-bromoethyl methyl ether was added (11.3 mL, 16.7 g, 120.2 mmol). The reaction mixture was allowed to warm overnight to room temperature. The reaction was quenched by addition of saturated aqueous NH Cl. The mixture was extracted with Et2O. The combined organic extracts were washed with water. The mixture was dried over Na2SO4. The mixture was filtered. The filtrate was concentrated at reduced pressure. The residue was chromatographed [silica, ethyl acetate/hexanes (1:19)] affording a viscous, colorless liquid (21.53 g, 96%): 1H NMR δ 1.84-1.93 (m, 1H), 1.96-2.03 (m, 2H), 2.07-2.15 (m, 1H), 2.78-2.93 (m, 4H), 3.34 (s, 3H), 3.51-3.55 (m, 4H), 4.19 (t, J=6.9 Hz, 1H); 13C NMR δ 26.16, 30.40, 35.58, 44.16, 58.84, 68.92; EI-MS: 178 (M+), 146, 133, 119/121, 71/73, 45. | COCCC1SCCCS1 | null | 96 | null |
6,406 | ord_dataset-653be8036d754ce7b8a1c4cd419eaf55 | null | 1976-01-01T00:05:00 | true | [C:1]([N:9]1[CH2:20][CH2:19][C:12]2[N:13]=[N:14][C:15]([NH:17][NH2:18])=[CH:16][C:11]=2[CH2:10]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:21][C:22]([CH3:24])=O>C(O)(=O)C>[C:1]([N:9]1[CH2:20][CH2:19][C:12]2[N:13]=[N:14][C:15]([NH:17][N:18]=[C:22]([CH3:24])[CH3:21])=[CH:16][C:11]=2[CH2:10]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1 | NNc1cc2c(nn1)CCN(C(=O)c1ccccc1)C2 | CC(C)=O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(=O)O | null | null | null | null | null | null | null | null | null | null | null | null | A solution of 0.5 g of 6-benzoyl-3-hydrazino-5,6,7,8-tetrahydropyrido[4,3-c]pyridazine in 15 cc of absolute acetone, to which 4 drops of glacial acetic acid have been added, is heated on a water bath for 1 hour. The solution is concentrated in a vacuum, and the crude title compound, obtained as an oil, is crystallized with ether. The title compound has a M.P. of 188°-190° (decomp.). | CC(C)=NNc1cc2c(nn1)CCN(C(=O)c1ccccc1)C2 | null | null | null |
1,639,783 | ord_dataset-f0794d5ded7a4d3fab45cc3d7a89ee3d | null | 2015-01-01T00:09:00 | true | [OH:1][CH2:2][C:3]1[N:7]([CH3:8])[N:6]=[C:5]([C:9]([O:11][CH3:12])=[O:10])[CH:4]=1.C(N(CC)CC)C.[CH3:20][S:21](Cl)(=[O:23])=[O:22]>C(Cl)Cl>[CH3:8][N:7]1[C:3]([CH2:2][O:1][S:21]([CH3:20])(=[O:23])=[O:22])=[CH:4][C:5]([C:9]([O:11][CH3:12])=[O:10])=[N:6]1 | COC(=O)c1cc(CO)n(C)n1 | CS(=O)(=O)Cl | 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 | 1 | To an ice-cooled solution of methyl 5-(hydroxymethyl)-1-methyl-1H-pyrazole-3-carboxylate (0.60 g, 3.51 mmol) and triethylamine (1.22 mL, 8.77 mmol) in DCM (10 mL) was added methanesulfonyl chloride (0.41 mL, 5.26 mmol). The reaction mixture was stirred in the ice bath for 15 minutes and then the mixture was allowed to warm to room temperature. The reaction mixture was stirred at RT for 1 hour. The reaction mixture was diluted with DCM and washed with water and brine. The organic phase was dried over magnesium sulfate, filtered and the solvent was evaporated in vacuo. The crude material was used in the next step without further purification. | COC(=O)c1cc(COS(C)(=O)=O)n(C)n1 | null | null | null |
1,223,198 | ord_dataset-cde802cdb7434a5f82a22981ccaefc4e | null | 2012-01-01T00:11:00 | true | [CH3:1][N:2]1[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:12]([N:14]3[CH2:18][CH2:17][C@@H:16]([NH:19]C(=O)OC(C)(C)C)[CH2:15]3)=[O:13])[CH:8]=2)[CH2:3]1.Cl>C1COCC1>[NH2:19][C@@H:16]1[CH2:17][CH2:18][N:14]([C:12]([C:7]2[CH:8]=[C:9]3[C:4](=[CH:5][CH:6]=2)[CH2:3][N:2]([CH3:1])[CH2:11][CH2:10]3)=[O:13])[CH2:15]1 | CN1CCc2cc(C(=O)N3CC[C@@H](NC(=O)OC(C)(C)C)C3)ccc2C1 | null | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | null | 2 | 1.4 g (3.8 mmol) tert. Butyl (R)-[1-(2-methyl-1,2,3,4-tetrahydroisoquinoline-6-carbonyl)-pyrrolidin-3-yl]-carbamate are dissolved in 5 ml THF and slowly combined with 9.5 ml hydrochloric acid (4 M in 1,4-dioxane). The mixture is stirred for two hours, then concentrated down to ⅔ of its volume and the crude product is filtered off as a precipitate, which is then purified by RP-HPLC (eluant: gradient ammonia/acetonitrile). | CN1CCc2cc(C(=O)N3CC[C@@H](N)C3)ccc2C1 | null | null | null |
424 | ord_dataset-a0eff6fe4b4143f284f0fc5ac503acad | null | 1976-01-01T00:01:00 | true | [C:1]([CH:4]1[CH2:9][CH2:8][CH:7]([CH3:10])[CH2:6][C:5]1=O)(=O)[CH3:2].[CH3:12][CH:13]([C:21]1[CH:22]=[C:23]([OH:28])[CH:24]=[C:25]([CH:27]=1)[OH:26])[CH:14]([CH3:20])[CH2:15][CH2:16][CH2:17][CH2:18][CH3:19].Cl>C(O)(=O)C>[CH3:12][CH:13]([C:21]1[CH:27]=[C:25]([OH:26])[C:24]2[CH:1]([CH3:2])[C:4]3[CH2:9][CH2:8][CH:7]([CH3:10])[CH2:6][C:5]=3[O:28][C:23]=2[CH:22]=1)[CH:14]([CH3:20])[CH2:15][CH2:16][CH2:17][CH2:18][CH3:19] | CC(=O)C1CCC(C)CC1=O | CCCCCC(C)C(C)c1cc(O)cc(O)c1 | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(=O)O | null | null | null | null | null | null | null | null | null | null | null | 20 | A solution of 3.6 g. of 2-acetyl-5 -methylcyclohexanone and 5.6 g. of 5-(1,2-dimethylheptyl)resorcinol in 150 ml. of acetic acid is cooled to 15° and saturated with hydrogen chloride gas. The solution is allowed to warm to 25°, stirred for 20 hours and then heated for one hour on a steam bath. The reaction mixture is concentrated in vacuo, water is added and the residue is dissolved in ethyl acetate. The ethyl acetate solution is washed with water, dried (MgSO4) and concentrated to give a residue which is distilled five times, b.p. 195°-200° (0.025 mm.). The distillate is chromatographed on silica gel with benzene as eluant. The second fraction is collected and distilled to give the title compound, b.p. 190°-195° (0.05 mm.). | CCCCCC(C)C(C)c1cc(O)c2c(c1)OC1=C(CCC(C)C1)C2C | null | null | null |
86,635 | ord_dataset-a0b0a122a04c40798e0535b968adcf6e | null | 1981-01-01T00:09:00 | true | [F-:1].[F:2][C:3]([F:14])([C:11](Cl)=[O:12])[O:4][C:5]([F:10])([F:9])[C:6](Cl)=[O:7].[F-:15].[Na+]>C(#N)C>[F:2][C:3]([F:14])([C:11]([F:15])=[O:12])[O:4][C:5]([F:10])([F:9])[C:6]([F:1])=[O:7] | O=C(Cl)C(F)(F)OC(F)(F)C(=O)Cl | [F-] | null | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC#N | null | null | null | null | null | null | null | null | null | null | null | 8 | Conversion of the diacid chloride to the corresponding fluoride, bp 32°-33° C., was accomplishd by a scale-up of the procedure of R. E. Banks, E. D. Burling, B. A. Dodd, and K. Mullen, J. Chem. Soc. (c), 1706 (1969). A mixture of 215 g 0.885 mol) of tetrafluorodiglycolyl dichloride, 140.5 g (3.35 mol) of NaF, and 1200 ml of anhydrous acetonitrile was stirred overnight, then distilled to give a fraction collected at 35°-79° C. The distillate was treated with 20 g of NaF and distilled to give 105 g of tetrafluorodiglycolyl difluoride, bp 32°-33° C. Addition of another 100 g (2.38 mol) of NaF to the reaction mixture and slow distillation afforded another fraction, bp 35°-81° C. Treatment with 10 g of NaF and fractionation gave another 37.0 g of difluoride product, bp 32°-33° C., for a total of 142 g (76%). | O=C(F)C(F)(F)OC(F)(F)C(=O)F | null | null | null |
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