original_index int64 2 1.77M | extracted_from_file stringclasses 489 values | date_of_experiment timestamp[ns]date | grant_date timestamp[ns]date 1976-01-01 00:01:00 2016-01-01 00:09:00 | is_mapped bool 1 class | rxn_str stringlengths 87 6.12k | reactant_000 stringlengths 1 902 | reactant_001 stringlengths 1 902 ⌀ | reactant_002 null | agent_000 stringlengths 1 540 ⌀ | agent_001 stringlengths 1 852 ⌀ | agent_002 stringlengths 1 247 ⌀ | agent_003 null | agent_004 null | agent_005 null | agent_006 null | agent_007 null | agent_008 null | agent_009 null | agent_010 null | agent_011 null | agent_012 null | agent_013 null | agent_014 null | agent_015 null | agent_016 null | solvent_000 stringclasses 446 values | solvent_001 stringclasses 405 values | solvent_002 null | solvent_003 null | solvent_004 null | solvent_005 null | solvent_006 null | solvent_007 null | solvent_008 null | solvent_009 null | solvent_010 null | temperature float64 -230 30.1k ⌀ | rxn_time float64 0 2.16k ⌀ | procedure_details stringlengths 8 24.5k | product_000 stringlengths 1 484 | product_001 null | yield_000 float64 0 90,205,156,600B ⌀ | yield_001 float64 0 100M ⌀ |
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15,735 | ord_dataset-b971427c0b944c56b63bb2356fa8ca69 | null | 1976-01-01T00:11:00 | true | [CH2:1]([CH:5]1[C:10](=O)[CH2:9][CH2:8][N:7]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:6]1)[C:2]([CH3:4])=O.[CH2:19]([NH2:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>>[CH2:19]([N:26]1[C:10]2[CH2:9][CH2:8][N:7]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH2:6][C:5]=2[CH:1]=[C:2]1[CH3:4])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1 | CC(=O)CC1CN(Cc2ccccc2)CCC1=O | NCc1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Using a procedure analogous to Example 3, 3-acetonyl-1-benzyl-4-piperidone may be reacted with benzylamine to give the title compound. | Cc1cc2c(n1Cc1ccccc1)CCN(Cc1ccccc1)C2 | null | null | null |
1,747,422 | ord_dataset-60a3e71da3174666a50a61dcfa611a9f | null | 2016-01-01T00:07:00 | true | [S:1]1[CH:5]=[CH:4][C:3]([C:6]2[CH:13]=[CH:12][C:9]([CH:10]=[O:11])=[CH:8][N:7]=2)=[CH:2]1.[CH3:14][Mg]Br>>[S:1]1[CH:5]=[CH:4][C:3]([C:6]2[N:7]=[CH:8][C:9]([CH:10]([OH:11])[CH3:14])=[CH:12][CH:13]=2)=[CH:2]1 | C[Mg]Br | O=Cc1ccc(-c2ccsc2)nc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Synthesized using compound 56b (260 mg, 1.37 mmol) and methylmagnesium bromide (2.74 mL, 2.74 mmol, 1 M in THF) according to Method D. Crude product was purified by flash chromatography on silica-gel using a mixture of hexane/ethyl acetate (1:1) as eluent. Yellow solid. Yield: 240 mg, 85%. 1H NMR (CDCl3, 500 MHz): δH (ppm)=1.50 (d, J=6.6 Hz, 3H), 4.90 (q, J=6.3 Hz, 1H), 7.38 (dd, J=5.0, 2.8 Hz, 1H), 7.55 (d, J=8.2 Hz, 1H), 7.61 (dd, J=5.0, 1.3 Hz, 1H), 7.70 (dd, J=8.2, 2.2 Hz, 1H), 7.85 (dd, J=2.8, 1.3 Hz, 1H), 8.48 (d, J=2.2 Hz, 1H); 13C NMR (CDCl3, 125 MHz): δC (ppm)=25.2, 68.0, 120.4, 123.6, 126.4, 126.5, 134.3, 139.5, 142.0, 147.4, 152.9; (ESI): m/z=206.29 [M+H]+. | CC(O)c1ccc(-c2ccsc2)nc1 | null | null | null |
1,205,034 | ord_dataset-fb72428f30234761b4216139dc228d0c | null | 2012-01-01T00:09:00 | true | [Cl:1][C:2]1[CH:3]=[C:4]([NH2:19])[CH:5]=[N:6][C:7]=1[O:8][C:9]1[CH:10]=[N:11][C:12]2[C:17]([CH:18]=1)=[CH:16][CH:15]=[CH:14][CH:13]=2.[CH3:20][O:21][C:22]1[CH:23]=[C:24]([S:30](Cl)(=[O:32])=[O:31])[CH:25]=[CH:26][C:27]=1[O:28][CH3:29]>>[Cl:1][C:2]1[CH:3]=[C:4]([NH:19][S:30]([C:24]2[CH:25]=[CH:26][C:27]([O:28][CH3:29])=[C:22]([O:21][CH3:20])[CH:23]=2)(=[O:32])=[O:31])[CH:5]=[N:6][C:7]=1[O:8][C:9]1[CH:10]=[N:11][C:12]2[C:17]([CH:18]=1)=[CH:16][CH:15]=[CH:14][CH:13]=2 | Nc1cnc(Oc2cnc3ccccc3c2)c(Cl)c1 | COc1ccc(S(=O)(=O)Cl)cc1OC | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The title compound was prepared by reacting 5-chloro-6-(quinolin-3-yloxy)pyridin-3-amine (obtained as per procedure described in preparation 1) and 3,4-dimethoxybenzene-1-sulfonyl chloride. | COc1ccc(S(=O)(=O)Nc2cnc(Oc3cnc4ccccc4c3)c(Cl)c2)cc1OC | null | null | null |
1,750,665 | ord_dataset-97eb2ab57fec4160922caae33b54d956 | null | 2016-01-01T00:08:00 | true | Cl.[F:2][C:3]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][C:4]=1[C@H:10]1[CH2:14][C@H:13]([F:15])[CH2:12][NH:11]1.Br[C:17]1[CH:22]=[CH:21][N:20]2[N:23]=[CH:24][C:25]([C:26]([O:28][CH2:29][CH3:30])=[O:27])=[C:19]2[CH:18]=1>>[F:2][C:3]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][C:4]=1[C@H:10]1[CH2:14][C@H:13]([F:15])[CH2:12][N:11]1[C:17]1[CH:22]=[CH:21][N:20]2[N:23]=[CH:24][C:25]([C:26]([O:28][CH2:29][CH3:30])=[O:27])=[C:19]2[CH:18]=1 | CCOC(=O)c1cnn2ccc(Br)cc12 | Fc1ccc(F)c([C@H]2C[C@H](F)CN2)c1 | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The title compound (Int-67) was prepared by the method similar to that for Int-84 using (2R,4S)-2-(2,5-difluorophenyl)-4-fluoropyrrolidine hydrochloride (Int-47) and Ethyl 5-bromopyrazolo[1,5-a]pyridine-3-carboxylate to afford as yellow solid. LCMS (ESI): m/z 390.8 (M+H). | CCOC(=O)c1cnn2ccc(N3C[C@@H](F)C[C@@H]3c3cc(F)ccc3F)cc12 | null | null | null |
718,645 | ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa | null | 2006-01-01T00:07:00 | true | [Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:12]=[C:11]([CH:13]3[CH2:18][O:17][CH2:16][CH2:15][NH:14]3)[O:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1.[S:19]1[CH:23]=[CH:22][N:21]=[C:20]1[CH:24]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:12]=[C:11]([CH:13]3[CH2:18][O:17][CH2:16][CH2:15][N:14]3[CH2:24][C:20]3[S:19][CH:23]=[CH:22][N:21]=3)[O:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1 | Clc1cccc(-c2noc(C3COCCN3)n2)c1 | O=Cc1nccs1 | null | CC(=O)O[BH-](OC(C)=O)OC(C)=O | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | 3-[3-(3-Chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-4-pyridin-2-ylmethyl-morpholine was obtained as described in Example 43 from (48 mg, 44%) 3-[3-(3-Chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-morpholine (80 mg, 0.30 mmol) with 2-thiazolecarboxaldehyde (68 mg, 0.60) and sodium triacetoxyborohydride (89 mg, 0.42 mmol). The product was purified by SPE chromatography on silica gel using 20–60% ethyl acetate in hexanes. 1H NMR (CDCl3), δ(ppm): 8.13 (s, 1H), 8.01 (d, 1H), 7.75 (d, 1H), 7.47 (m, 2H), 7.33 (d, 1H), 4.29 (m, 1H), 4.15 (m, 4H), 3.88 (m, 2H), 3.30 (m, 1H), 2.70 (m, 1H). | Clc1cccc(-c2noc(C3COCCN3Cc3nccs3)n2)c1 | null | null | null |
870,900 | ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b | null | 2009-01-01T00:03:00 | true | [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[N:11]([CH3:25])[C:12]([S:15][CH2:16][CH2:17][CH2:18][N:19]3[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]3)=[N:13][CH:14]=2)=[O:9])=[CH:4][CH:3]=1>O=[Mn]=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:10]2[N:11]([CH3:25])[C:12]([S:15][CH2:16][CH2:17][CH2:18][N:19]3[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]3)=[N:13][CH:14]=2)[OH:9])=[CH:4][CH:3]=1 | Cn1c(C(=O)c2ccc(Br)cc2)cnc1SCCCN1CCCCC1 | null | null | O=[Mn]=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 | The product of Example III, Step B (0.11 g) in acetone (5 mL) and DMF (5 mL) was treated with piperidine (0.22 g) and K2CO3 (1.8 g). The reaction mixture was allowed to stir for 16 h and then partitioned between EtOAc (75 mL) and aqueous (aq.) saturated (satd.) NaHCO3 (50 mL). The organic portion was washed with brine (50 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using 2-5% MeOH/CH2Cl2 as the eluent to provide the title compound (0.27 g, 55%). M calc=423; M+H found=424. Step D: (4-Bromophenyl)-[3-methyl-2-(3-piperidin-1-yl-propylsulfanyl)-3H-imidazol-4-yl]-methanone. The product from Example III, Step C (0.05 g) was subjected to the same conditions described in Example I, Step C (MnO2, 0.05g) to provide the title compound (0.01 g, 20%). M calc=421; M+H found=422. 1H NMR (400 MHz, CDCl3): δ 7.65 (dd, J=8.6, 2.0 Hz, 2H), 7.55 (dd, J=8.6, 2.0 Hz, 2H), 7.46 (s, 1H), 3.86 (s, 3H), 3.28 (t, J=7.1 Hz, 2H), 2.36 (tm, J=7.0 Hz, 6H), 1.91 (m, 2H), 1.55 (m, 4H), 1.40 (br m, 2H). The compound demonstrated useful biological activity when assessed with a [3H]—N-methylhistamine binding assay (see Table in Example XXV). Step E: Additional compounds prepared following Scheme I, and Example III, Steps A, B, C, and D. The following compounds of formula (I) were prepared following Scheme I and Example III, Steps A, B, C, and D; and substituting reagents, and adjusting reaction conditions as needed. The compounds were found to have useful biological activity based on the Ki (nM) value from a [3H]-N-methylhistamine binding assay. | Cn1c(C(O)c2ccc(Br)cc2)cnc1SCCCN1CCCCC1 | null | 20 | null |
1,310,993 | ord_dataset-2d6edb8ffd434003bb508360153bd9bb | null | 2013-01-01T00:07:00 | true | Br[C:2]1[CH:11]=[CH:10][C:9]2[N:8]=[CH:7][C:6]3[N:12]([CH3:23])[C:13](=[O:22])[N:14]([C:15]4[C:16]([CH3:21])=[N:17][N:18]([CH3:20])[CH:19]=4)[C:5]=3[C:4]=2[CH:3]=1.[CH:24]([O:27][C:28]1[CH:29]=[C:30](B(O)O)[CH:31]=[CH:32][CH:33]=1)([CH3:26])[CH3:25]>>[CH3:20][N:18]1[CH:19]=[C:15]([N:14]2[C:5]3[C:4]4[CH:3]=[C:2]([C:32]5[CH:31]=[CH:30][CH:29]=[C:28]([O:27][CH:24]([CH3:26])[CH3:25])[CH:33]=5)[CH:11]=[CH:10][C:9]=4[N:8]=[CH:7][C:6]=3[N:12]([CH3:23])[C:13]2=[O:22])[C:16]([CH3:21])=[N:17]1 | Cc1nn(C)cc1-n1c(=O)n(C)c2cnc3ccc(Br)cc3c21 | CC(C)Oc1cccc(B(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 | null | null | The title compound was synthesized in a similar manner as described for Example 1.1 using 8-bromo-1-(1,3-dimethyl-1H-pyrazol-4-yl)-3-methyl-1,3-dihydro-imidazo[4,5-c]quinolin-2-one (Intermediate A) and 3-isopropoxyphenylboronic acid (Aldrich, Buchs, Switzerland) to give the title compound as a white solid. (HPLC: tR 2.95 min (Method A); M+H=428 MS-ES; 1H-NMR (d6-DMSO, 400 MHz) 8.96 (s, 1H), 8.19-8.16 (m, 1H), 8.09-8.05 (m, 1H), 7.94-7.89 (m, 1H), 7.57-7.54 (m, 1H), 7.39-7.33 (m, 1H), 7.10-7.06 (m, 1H), 6.94-9-6.90 (m, 2H), 4.68 (hp, 1H), 3.92 (s, 3H), 3.57 (s, 3H), 1.95 (s, 3H), 1.30 (t, 6H)) | Cc1nn(C)cc1-n1c(=O)n(C)c2cnc3ccc(-c4cccc(OC(C)C)c4)cc3c21 | null | null | null |
1,147,659 | ord_dataset-b195433d5c354ddfb6cde0d53c41910f | null | 2012-01-01T00:04:00 | true | [Cl:1][C:2]1[N:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[F:9].CN(C)C=O.C(=O)([O-])[O-].[K+].[K+].[CH2:21](Br)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>O>[Cl:1][C:2]1[C:3]([F:9])=[CH:4][C:5]([O:8][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[CH:6][N:7]=1 | BrCc1ccccc1 | Oc1cnc(Cl)c(F)c1 | null | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CN(C)C=O | null | null | null | null | null | null | null | null | null | 80 | null | 0.5 g (3.38 mM) of 6-chloro-5-fluoro-3-pyridinol, 10 ml of dimethyl-formamide and 0.843 g (6.08 mM) of potassium carbonate are mixed. 0.8 ml (6.76 mM) of benzyl bromide is added and the mixture is heated at 80° C. for one hour. After hydrolysis in 100 ml of water, the mixture is extracted with ethyl acetate and the organic phases are washed with water, dried over magnesium sulfate and concentrated under reduced pressure. The crude product is purified by chromatography on silica gel (eluent: pure toluene) to give the expected product in the form of a white solid with a quantitative yield. | Fc1cc(OCc2ccccc2)cnc1Cl | null | null | null |
1,113,348 | ord_dataset-375a420ee9b042918ddca20f02df37d3 | null | 2011-01-01T00:11:00 | true | [O:1]=[C:2]([NH:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([F:29])([F:28])[F:27])[CH:21]=1)[CH2:3][NH:4][C:5]([C@@H:7]1[CH2:11][CH2:10][N:9](C(OC(C)(C)C)=O)[CH2:8]1)=[O:6].[ClH:30].O1CCOCC1>O1CCOCC1>[ClH:30].[O:1]=[C:2]([NH:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([F:29])([F:27])[F:28])[CH:21]=1)[CH2:3][NH:4][C:5]([C@@H:7]1[CH2:11][CH2:10][NH:9][CH2:8]1)=[O:6] | CC(C)(C)OC(=O)N1CC[C@@H](C(=O)NCC(=O)Nc2cccc(C(F)(F)F)c2)C1 | null | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1COCCO1 | null | null | null | null | null | null | null | null | null | null | 25 | 2 | To a solution of tert-butyl (3R)-3-{[(2-oxo-2-{[3-(trifluoromethyl)phenyl]amino}ethyl)amino]carbonyl}pyrrolidine-1-carboxylate (0.170 g, 0.41 mmol) in dioxane (0.5 ml), was added 4M HCl/dioxane (2 mL). The mixture was stirred at RT for 2 h. The mixture was concentrated, and (3R)—N-(2-oxo-2-{[3-(trifluoromethyl)phenyl]amino}ethyl)pyrrolidine-3-carboxamide hydrochloride was obtained as a white solid and was used in the next step without further purification. | O=C(CNC(=O)[C@@H]1CCNC1)Nc1cccc(C(F)(F)F)c1 | null | null | null |
910,255 | ord_dataset-46d216f2c4374ef5b9df90427e2a4cd4 | null | 2009-01-01T00:09:00 | true | [C:1]1([C:7]2[C:11]3[CH:12]=[N:13][CH:14]=[CH:15][C:10]=3[NH:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[F:16][C:17]1[CH:36]=[CH:35][C:20]([CH2:21][NH:22][C:23]([C:25]2[CH:30]=[CH:29][C:28]([S:31](Cl)(=[O:33])=[O:32])=[CH:27][CH:26]=2)=[O:24])=[CH:19][CH:18]=1>C1COCC1>[F:16][C:17]1[CH:18]=[CH:19][C:20]([CH2:21][NH:22][C:23](=[O:24])[C:25]2[CH:30]=[CH:29][C:28]([S:31]([N:9]3[C:10]4[CH:15]=[CH:14][N:13]=[CH:12][C:11]=4[C:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)=[CH:8]3)(=[O:32])=[O:33])=[CH:27][CH:26]=2)=[CH:35][CH:36]=1 | c1ccc(-c2c[nH]c3ccncc23)cc1 | O=C(NCc1ccc(F)cc1)c1ccc(S(=O)(=O)Cl)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | null | null | Add a 5 ml THF solution of 3-Phenyl-1H-pyrrolo[3,2-c]pyridine (500 mg, 2.57 mmol, 1 eq) to a 4 ml THF solution of KotBu (303 mg, 2.70 mmol, 1.05 eq) under N2 atmosphere. Stir reaction for 10 minutes and then add a 5 ml THF solution of 4-(4-Fluoro-benzylcarbamoyl)-benzenesulfonyl chloride (844 mg, 2.57 mmol, 1 eq). Stir reaction for 16 hours, remove solvent on rotovap, and purify by silica gel chromatography to give N-(4-Fluoro-benzyl)-4-(3-phenyl-pyrrolo[3,2-c]pyridine-1-sulfonyl)-benzamide (982 mg, 79% yield). Mass Spectrum (m/e): 485.96 (MH+). | O=C(NCc1ccc(F)cc1)c1ccc(S(=O)(=O)n2cc(-c3ccccc3)c3cnccc32)cc1 | null | 78.7 | null |
63,418 | ord_dataset-9240b22758dd4f9e981f9ad2d5394155 | null | 1980-01-01T00:02:00 | true | [CH:1]#[C:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].CC(N=NC(C#N)(C)C)(C#N)C.[CH2:21]([SnH:25]([CH2:30][CH2:31][CH2:32][CH3:33])[CH2:26][CH2:27][CH2:28][CH3:29])[CH2:22][CH2:23][CH3:24]>C1(C)C=CC=CC=1>[CH2:30]([Sn:25]([CH2:21][CH2:22][CH2:23][CH3:24])([CH2:26][CH2:27][CH2:28][CH3:29])/[CH:1]=[CH:2]/[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8])[CH2:31][CH2:32][CH3:33] | CCCC[SnH](CCCC)CCCC | C#CCCCCCC | null | CC(C)(C#N)N=NC(C)(C)C#N | 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 | 25 | null | A solution of 10.0 g (0.0908 mol) of 1-octyne, 60 ml of anhydrous toluene, 230 mg of azobisisobutylonitrile (AIBN), and 25 (0.0943 mol) of tri-n-butyltin hydride is refluxed under an argon atomosphere for 3 hours. The reaction mixture is cooled to ambient temperature and concentrated in vacuo. The resulting yellow liquid is distilled (bulb to bulb) to give 36.29 (99%) of the stannyl octene as a pale yellow liquid. | CCCCCC/C=C/[Sn](CCCC)(CCCC)CCCC | null | null | null |
813,600 | ord_dataset-892acf7477db4d3a8a8559f004a7c0a2 | null | 2008-01-01T00:03:00 | true | [CH3:1][N:2]([CH3:16])[C:3]1([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:8][CH2:7][CH:6]([NH2:9])[CH2:5][CH2:4]1.[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1.[NH:35]1[C:43]2[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=2)[C:37]([CH2:44][C:45]([NH:47][C@H:48]([C:53](O)=[O:54])[CH2:49][CH:50]([CH3:52])[CH3:51])=[O:46])=[CH:36]1>CO>[CH3:1][N:2]([CH3:16])[C:3]1([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:8][CH2:7][CH:6]([NH:9][C:53](=[O:54])[CH:48]([NH:47][C:45](=[O:46])[CH2:44][C:37]2[C:38]3[C:43](=[CH:42][CH:41]=[CH:40][CH:39]=3)[NH:35][CH:36]=2)[CH2:49][CH:50]([CH3:52])[CH3:51])[CH2:5][CH2:4]1 | CC(C)C[C@H](NC(=O)Cc1c[nH]c2ccccc12)C(=O)O | CN(C)C1(c2ccccc2)CCC(N)CC1 | null | COc1nc(OC)nc([N+]2(C)CCOCC2)n1 | [Cl-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | 25 | 24 | The more polar diastereomer of (4-dimethylamino-4-phenyl-cyclohexyl)amine (143 mg, 0.66 mmole) and 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (272 mg, 0.98 mmole) were added to a solution of N-(3-indolylacetyl)-L-leucine (189 mg, 0.66 mmole) in MeOH and stirred for 24 h at room temperature. Working up was performed by removing MeOH by distillation. The residue was re-dissolved with water, adjusted to pH 11 with 5M NaOH and extracted with ethyl acetate. The organic phase was dried with Na2SO4 and then evaporated. The product was obtained as a colorless oil in a yield of 320 mg (100%). | CC(C)CC(NC(=O)Cc1c[nH]c2ccccc12)C(=O)NC1CCC(c2ccccc2)(N(C)C)CC1 | null | null | null |
1,615,689 | ord_dataset-35c51552812941cda45194a013d34bb9 | null | 2015-01-01T00:08:00 | true | [Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8](Cl)=[N:9]2)=[N:4][CH:3]=1.[NH:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1>C(OCC)(=O)C>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[N:9]2)=[N:4][CH:3]=1 | Clc1ccc2ncc(Br)cc2n1 | C1COCCN1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOC(C)=O | null | null | null | null | null | null | null | null | null | null | 140 | 8 | A mixture of 7-bromo-2-chloro-1,5-naphthyridine (F-31) (200 mg, 0.82 mmol, 1.0 eq) and morpholine (10 mL) was stirred in a sealed-tube at 140° C. overnight. The reaction mixture was cooled to RT, diluted with ethyl acetate (150 mL) and then washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo to afford the desired product 7-bromo-2-morpholino-1,5-naphthyridine (F-32) (180 mg, 74.7% yield). ESI-MS m/z: 294.01 [M+H]+. | Brc1cnc2ccc(N3CCOCC3)nc2c1 | null | 74.7 | null |
1,567,131 | ord_dataset-4e54080057a44c3887653391e24c90b6 | null | 2015-01-01T00:03:00 | true | [CH3:1][C:2]1[N:3]=[C:4]([C:7]2[C:15]3[C:14]([C:16]4[CH:21]=[CH:20][CH:19]=[C:18]([N+:22]([O-])=O)[CH:17]=4)=[N:13][CH:12]=[N:11][C:10]=3[N:9]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[CH:8]=2)[O:5][CH:6]=1>CO.[OH-].[OH-].[Pd+2]>[CH3:1][C:2]1[N:3]=[C:4]([C:7]2[C:15]3[C:14]([C:16]4[CH:17]=[C:18]([CH:19]=[CH:20][CH:21]=4)[NH2:22])=[N:13][CH:12]=[N:11][C:10]=3[N:9]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:30])([CH3:32])[CH3:31])[CH:8]=2)[O:5][CH:6]=1 | Cc1coc(-c2cn(COCC[Si](C)(C)C)c3ncnc(-c4cccc([N+](=O)[O-])c4)c23)n1 | null | null | [Pd+2] | [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 | 4 | To a solution of 4-methyl-2-(4-(3-nitrophenyl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)oxazole (0.30 g, 0.66 mmol) in methanol (20 mL), was added Pd(OH)2 on carbon (300 mg, 10 wt. %). The flask was purged with hydrogen and was stirred for 4 hours at room temperature under hydrogen atmosphere (1 atm). The reaction was filtered, and concentrated in vacuo to afford crude 3-(5-(4-methyloxazol-2-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)aniline as a colorless oil. LRMS (ESI) calc'd for C22H28N5O2Si [M+H]+: 422, found 422. | Cc1coc(-c2cn(COCC[Si](C)(C)C)c3ncnc(-c4cccc(N)c4)c23)n1 | null | null | null |
1,390,519 | ord_dataset-31641fb65b34430fa7435229b949b604 | null | 2014-01-01T00:01:00 | true | [CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][C:12]=1[O:13][CH2:14][CH3:15])[C:7]([NH2:9])=[O:8])[CH3:2].Br[CH2:17][C:18](=O)[CH2:19][CH2:20][C:21]([O:23][CH3:24])=[O:22]>CN(C)C=O>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:7]2[O:8][CH:17]=[C:18]([CH2:19][CH2:20][C:21]([O:23][CH3:24])=[O:22])[N:9]=2)[CH:10]=[CH:11][C:12]=1[O:13][CH2:14][CH3:15])[CH3:2] | CCOc1ccc(C(N)=O)cc1OCC | COC(=O)CCC(=O)CBr | null | null | 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 | 130 | 16 | A 40 g quantity of 3,4-diethoxybenzamide and 80 g of methyl 5-bromo-4-oxopentanoate (containing about 35% of methyl 3-bromo-4-oxopentanoate) were added to 400 ml of dimethylformamide, and the mixture was stirred at 130° C. for 16 hours. The reaction mixture was concentrated under reduced pressure and diluted with ethyl acetate. Ethyl acetate (500 ml) and saturated sodium bicarbonate solution (500 ml) were gradually added with stirring, and stirring was continued. The organic layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:n-hexane=1:8 to 1:4) to give 18 g of white powdery methyl 3-[2-(3,4-diethoxyphenyl)oxazol-4-yl]propionate. | CCOc1ccc(-c2nc(CCC(=O)OC)co2)cc1OCC | null | null | null |
1,216,060 | ord_dataset-dc3bb1b1ac4e4229a3fc28fb559a9777 | null | 2012-01-01T00:10:00 | true | [N+:1]([C:4]1[CH:56]=[CH:55][C:7]([O:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[C:16]4[NH:20][C:19]([CH:21]=[C:22]5[N:54]=[C:25]([C:26]([C:38]6[CH:43]=[CH:42][C:41]([O:44][C:45]7[CH:50]=[CH:49][C:48]([N+:51]([O-])=O)=[CH:47][CH:46]=7)=[CH:40][CH:39]=6)=[C:27]6[NH:37][C:30](=[CH:31][C:32]7[CH:33]=[CH:34][C:35]=3[N:36]=7)[CH:29]=[CH:28]6)[CH:24]=[CH:23]5)=[CH:18][CH:17]=4)=[CH:11][CH:10]=2)=[CH:6][CH:5]=1)([O-])=O.Cl.O.O.Cl[Sn]Cl.N>C(Cl)(Cl)Cl.O>[NH2:1][C:4]1[CH:56]=[CH:55][C:7]([O:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[C:16]4[NH:20][C:19]([CH:21]=[C:22]5[N:54]=[C:25]([C:26]([C:38]6[CH:43]=[CH:42][C:41]([O:44][C:45]7[CH:50]=[CH:49][C:48]([NH2:51])=[CH:47][CH:46]=7)=[CH:40][CH:39]=6)=[C:27]6[NH:37][C:30](=[CH:31][C:32]7[CH:33]=[CH:34][C:35]=3[N:36]=7)[CH:29]=[CH:28]6)[CH:24]=[CH:23]5)=[CH:18][CH:17]=4)=[CH:11][CH:10]=2)=[CH:6][CH:5]=1 | O=[N+]([O-])c1ccc(Oc2ccc(-c3c4nc(cc5ccc([nH]5)c(-c5ccc(Oc6ccc([N+](=O)[O-])cc6)cc5)c5nc(cc6ccc3[nH]6)C=C5)C=C4)cc2)cc1 | null | null | Cl | Cl[Sn]Cl | N | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClC(Cl)Cl | O | null | null | null | null | null | null | null | null | null | null | 24 | To a solution of 5,15-bis-[4-(4-nitrophenoxy)phenyl]porphyrin (70 mg, 0.095 mmol) in CHCl3 (10 ml), saturated with concentrated HCl, SnCl2.2H2O (105 mg, 0.475 mmol) was added and the mixture was kept under magnetic stirring, at room temperature for 24 h, then cold water was added, the mixture was neutralized with a solution 15% of ammonia, and the organic phase was extracted, dried on Na2SO4, then the solvent was removed by evaporation. The crude product was purified by chromatography on silica gel (THF to THF/DMF 9/1), to give 43 mg of title product (yield 67%). | Nc1ccc(Oc2ccc(-c3c4nc(cc5ccc([nH]5)c(-c5ccc(Oc6ccc(N)cc6)cc5)c5nc(cc6ccc3[nH]6)C=C5)C=C4)cc2)cc1 | null | 66.9 | null |
461,823 | ord_dataset-5ca9db262dd24c5a9315cdc8ef055b7e | null | 2000-01-01T00:04:00 | true | [CH3:1][CH:2]([C:4](=[O:16])[CH2:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([N+:13]([O-])=O)=[CH:9][CH:8]=1)[CH3:3].[H][H]>[Ni].C1COCC1>[NH2:13][C:10]1[CH:9]=[CH:8][C:7]([CH2:6][CH2:5][C:4](=[O:16])[CH:2]([CH3:1])[CH3:3])=[CH:12][CH:11]=1 | CC(C)C(=O)CCc1ccc([N+](=O)[O-])cc1 | [H][H] | null | [Ni] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | null | null | A mixture of 13.6 g (62 mmol) of 2-methyl-5-(4-nitro-phenyl)-pentan-3-one (Y. Huang, L. Shi, S. Li, Synthesis, 1988, 975-977), 400 mL of THF, and 2.6 g of Raney Nickel was shaken in a hydrogen atmosphere (24 p.s.i.) at 25° C. for 56 hours. The catalyst was filtered, and the filtrate was concentrated to give the title compound. 1H NMR (CDCl3) δ 1.01 (d, 6 H), 2.46-2.55 (m, 1 H), 2.65-2.83 (m, 4 H), 3.55 (br s , 2 H), 6.56 (d, 2 H), 6.92 (d, 2 H). | CC(C)C(=O)CCc1ccc(N)cc1 | null | null | null |
204,193 | ord_dataset-76a008eb2d3f48d891cad325041f3d1e | null | 1990-01-01T00:02:00 | true | [CH3:1]/[CH:2]=[C:3](/[C:5]([O:7][C@@H:8]1[C@:16]23[C@H:20]([C@@:21]([C@:25]45[O:30][C@@:29]4([CH3:31])[C@H:28]4[C@:32]6([OH:38])[C@H:36]([O:37][C@@H:26]5[CH2:27]4)[O:35][CH:34]=[CH:33]6)([CH3:24])[C@H:22]([OH:23])[C@H:14]4[C@H:15]2[C@:11]([C:44]([O:46][CH3:47])=[O:45])([CH2:12][O:13]4)[C@H:10]([O:48][C:49]([CH3:51])=[O:50])[CH2:9]1)[C@@:19]([OH:43])([C:39]([O:41][CH3:42])=[O:40])[O:18][CH2:17]3)=[O:6])\[CH3:4].[H][H]>O.O.[Pt](=O)=O.C(OCC)(=O)C>[CH3:1]/[CH:2]=[C:3](/[C:5]([O:7][C@@H:8]1[C@:16]23[C@H:20]([C@@:21]([C@:25]45[O:30][C@@:29]4([CH3:31])[C@@H:28]4[C@:32]6([OH:38])[C@@H:36]([O:37][C@H:26]5[CH2:27]4)[O:35][CH2:34][CH2:33]6)([CH3:24])[C@H:22]([OH:23])[C@H:14]4[C@H:15]2[C@:11]([C:44]([O:46][CH3:47])=[O:45])([CH2:12][O:13]4)[C@H:10]([O:48][C:49]([CH3:51])=[O:50])[CH2:9]1)[C@@:19]([OH:43])([C:39]([O:41][CH3:42])=[O:40])[O:18][CH2:17]3)=[O:6])\[CH3:4] | [H][H] | C/C=C(\C)C(=O)O[C@H]1C[C@@H](OC(C)=O)[C@@]2(C(=O)OC)CO[C@H]3[C@@H](O)[C@@](C)([C@]45O[C@@]4(C)[C@@H]4C[C@H]5O[C@@H]5OC=C[C@@]54O)[C@H]4[C@]1(CO[C@]4(O)C(=O)OC)[C@@H]32 | null | O=[Pt]=O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOC(C)=O | O | null | null | null | null | null | null | null | null | null | null | 1.25 | 40.8 mg. azadirachtin A (5.67×1031 5 mole) were dissolved in 4 ml. ethyl acetate and 20 mg. platinum dioxide dihydrate were added thereto. The mixture was stirred and hydrogen passed therethrough for 75 minutes, the course of the reaction being monitored by HPLC. After the disappearance of the azadirachtin A peak, the reaction was discontinued and the reaction mixture centrifuged. The supernatant solution was evaporated and purified on silicon dioxide thin layer chromatography plates using the elution agent chloroform/acetone (7:3 v/v); Rf 0.33. Yield: 28.2 mg. (69% of theory). | C/C=C(\C)C(=O)O[C@H]1C[C@@H](OC(C)=O)[C@@]2(C(=O)OC)CO[C@H]3[C@@H](O)[C@@](C)([C@]45O[C@@]4(C)[C@H]4C[C@@H]5O[C@H]5OCC[C@@]54O)[C@H]4[C@]1(CO[C@]4(O)C(=O)OC)[C@@H]32 | null | null | null |
1,749,000 | ord_dataset-60a3e71da3174666a50a61dcfa611a9f | null | 2016-01-01T00:07:00 | true | CO[C:3]([C:5]1[CH:10]=[N:9][CH:8]=[CH:7][N:6]=1)=[O:4].[C:11](#[N:13])[CH3:12].[H-].[Na+:15].C(OC)(C)(C)C>C1COCC1>[C:11]([CH:12]=[C:3]([C:5]1[CH:10]=[N:9][CH:8]=[CH:7][N:6]=1)[O-:4])#[N:13].[Na+:15] | CC#N | COC(=O)c1cnccn1 | null | [H-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | COC(C)(C)C | null | null | null | null | null | null | null | null | null | null | 0.5 | A solution of 1.5 g (10.9 mmol) of methylpyrazine-2-carboxylate and 446 mg (10.9 mmol) of acetonitrile in 16.5 ml of THF was added dropwise to a suspension, heated under reflux, of 434 mg of sodium hydride (60% strength suspension in mineral oil) in 10 ml of THF. The reaction mixture was heated under reflux for 20 h. After cooling, 50 ml of methyl tert-butyl ether were added and the mixture was stirred for 30 minutes. The precipitate formed was filtered off with suction over a frit and dried under oil pump vacuum. This gave 1.77 g (96% of theory) of the title compound which was used without further characterization for the next step. | N#CC=C([O-])c1cnccn1 | null | null | null |
1,733,217 | ord_dataset-eacfee6d16d8455a93348409f1b37be4 | null | 2016-01-01T00:06:00 | true | [Si]([O:8][CH2:9][CH:10]([O:44][CH3:45])[CH2:11][N:12]1[C:20](=[O:21])[C:19]2[N:18]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=3)[C:17]([O:30][C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([O:37][C:38]([F:41])([F:40])[F:39])[CH:32]=3)=[N:16][C:15]=2[N:14]([CH3:42])[C:13]1=[O:43])(C(C)(C)C)(C)C.Cl>C(O)C>[Cl:29][C:26]1[CH:25]=[CH:24][C:23]([CH2:22][N:18]2[C:19]3[C:20](=[O:21])[N:12]([CH2:11][CH:10]([O:44][CH3:45])[CH2:9][OH:8])[C:13](=[O:43])[N:14]([CH3:42])[C:15]=3[N:16]=[C:17]2[O:30][C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([O:37][C:38]([F:41])([F:39])[F:40])[CH:32]=2)=[CH:28][CH:27]=1 | COC(CO[Si](C)(C)C(C)(C)C)Cn1c(=O)c2c(nc(Oc3cccc(OC(F)(F)F)c3)n2Cc2ccc(Cl)cc2)n(C)c1=O | null | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | null | null | null | null | null | null | null | null | null | null | null | 0.17 | To a solution of 1-(3-(tert-butyldimethylsilyloxy)-2-methoxypropyl)-7-(4-chlorobenzyl)-3-methyl-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione (150 mg, 0.22 mmol) in ethyl alcohol (5 mL) was added concentrated HCl (0.1 mL). The reaction was stirred for 10 minutes. Then it was concentrated and purified by preparative HPLC to give 7-(4-chlorobenzyl)-1-(3-hydroxy-2-methoxypropyl)-3-methyl-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione (18 mg, 16.2% yield) as white solid. 1H-NMR (DMSO-d6) δ 7.63-7.59(t, 1H), 7.50(s, 1H), 7.45-7.43(m, 5H), 7.34-7.32(d, 1H), 5.44(s, 2H), 4.65-4.62(t, 1H), 4.12-4.08(q, 1H), 3.84-3.79(q, 1H), 3.53-3.41(m, 2H), 3.29-3.28(d, 6H). LCMS retention time 3.089 min; LCMS MH+ 555. | COC(CO)Cn1c(=O)c2c(nc(Oc3cccc(OC(F)(F)F)c3)n2Cc2ccc(Cl)cc2)n(C)c1=O | null | 14.7 | null |
1,053,862 | ord_dataset-373415d3e0e54004837cf4831e67666f | null | 2011-01-01T00:05:00 | true | [C:1]1([C:6]2[CH:30]=[CH:29][C:9]([C:10]([NH:12][CH2:13][C:14]3[C:15]([CH2:20][NH:21]C(=O)OC(C)(C)C)=[N:16][CH:17]=[CH:18][CH:19]=3)=[O:11])=[C:8]([NH:31][CH2:32][CH2:33][C:34]3[CH:39]=[CH:38][CH:37]=[C:36]([F:40])[CH:35]=3)[N:7]=2)[CH2:5][CH2:4][CH2:3][CH:2]=1.Cl.O1CCOCC1>CO>[NH2:21][CH2:20][C:15]1[C:14]([CH2:13][NH:12][C:10](=[O:11])[C:9]2[CH:29]=[CH:30][C:6]([C:1]3[CH2:5][CH2:4][CH2:3][CH:2]=3)=[N:7][C:8]=2[NH:31][CH2:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([F:40])[CH:35]=2)=[CH:19][CH:18]=[CH:17][N:16]=1 | CC(C)(C)OC(=O)NCc1ncccc1CNC(=O)c1ccc(C2=CCCC2)nc1NCCc1cccc(F)c1 | null | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | C1COCCO1 | null | null | null | null | null | null | null | null | null | 25 | null | tert-butyl (3-((6-cyclopentenyl-2-(3-fluorophenethylamino)nicotinamido)methyl)pyridin-2-yl)methylcarbamate was dissolved in MeOH (1 mL) and allowed to stir at room temperature. HCl/dioxane (4M, 2 mL) was added dropwise and stirred until complete. The reaction mixture was concentrated, diluted with EtOAc, washed with saturated sodium bicarbonate, brine and dried (Na2SO4). The organics were concentrated and purified by RP-HPLC with a mixture of acetonitrile and H2O to give N-((2-(aminomethyl)pyridin-3-yl)methyl)-6-cyclopentenyl-2-(3-fluorophenethylamino)nicotinamide as a solid (0.026 g, 25%). LC/MS (M+H+) m/z 446.2. | NCc1ncccc1CNC(=O)c1ccc(C2=CCCC2)nc1NCCc1cccc(F)c1 | null | 25 | null |
1,137,467 | ord_dataset-aaeaab5f3720492494c1cbbdd0ed2820 | null | 2012-01-01T00:02:00 | true | [Br:1][C:2]1[CH:10]=[C:9]([F:11])[C:8]([F:12])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].S(=O)(=O)(O)O.[CH3:18]O>>[CH3:18][O:5][C:4](=[O:6])[C:3]1[CH:7]=[C:8]([F:12])[C:9]([F:11])=[CH:10][C:2]=1[Br:1] | CO | O=C(O)c1cc(F)c(F)cc1Br | 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 | 80 | null | To a solution of 2-bromo-4,5-difluoro-benzoic acid (5 g, 21.10 mmol) in methanol (100 mL) was added concentrated sulfuric acid (0.21 mL, 2.11 mmol) at 0° C. The reaction mixture was then heated at 80° C. for 4 hours. After cooling to room temperature, the mixture was poured into ice water, and extracted with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate, then brine, dried over sodium sulfate, filtered, and concentrated to afford the crude product 2-bromo-4,5-difluoro-benzoic acid methyl ester (1.48 g, 28%) as a clear oil, which was used in the next step without further purification. | COC(=O)c1cc(F)c(F)cc1Br | null | 28 | null |
84,120 | ord_dataset-7bed824f566d4af0b51d74d386b14bd6 | null | 1981-01-01T00:07:00 | true | [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:14]2[CH:15]=[C:16]([NH:19][C:20]([N:22]3[CH2:24][CH2:23]3)=[O:21])[CH:17]=[CH:18][C:13]=2[N:12]([CH3:25])[C:11](=[O:26])[CH2:10][N:9]=1.S(=O)(=O)(O)O.C(=O)(O)[O-].[Na+].[C:37]([OH:41])([CH3:40])([CH3:39])[CH3:38]>>[C:37]([O:41][CH2:24][CH2:23][NH:22][C:20]([NH:19][C:16]1[CH:17]=[CH:18][C:13]2[N:12]([CH3:25])[C:11](=[O:26])[CH2:10][N:9]=[C:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[F:1])[C:14]=2[CH:15]=1)=[O:21])([CH3:40])([CH3:39])[CH3:38] | CC(C)(C)O | CN1C(=O)CN=C(c2ccccc2F)c2cc(NC(=O)N3CC3)ccc21 | null | O=C([O-])O | O=S(=O)(O)O | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | 0.33 | 2 g (0.0057 M) of N-[5-(o-fluorophenyl)-2,3-dihydro-1-methyl-2-oxo-1H-1,4-benzodiazepin-7-yl]-1-aziridinecarboxamide in 50 ml of tert.butanol are treated with 3 ml of 25% sulphuric acid. After 20 minutes, the mixture is made alkaline with 10% sodium bicarbonate solution and extracted several times with methylene chloride. The methylene chloride solution is dried over sodium sulphate, filtered and concentrated. The residue is purified on a 80 g silica gel column using ethyl acetate as the eluting agent and recrystallised from ethyl acetate. There is obtained 1-(2-tert.butoxyethyl)-3-[5-(o-fluorophenyl)-2,3-dihydro-1-methyl-2-oxo-1H-1,4-benzodiazepin-7-yl]urea which melts at 177° C. | CN1C(=O)CN=C(c2ccccc2F)c2cc(NC(=O)NCCOC(C)(C)C)ccc21 | null | null | null |
1,247,551 | ord_dataset-c544c0c663f54dbea4ddb52ddde7934e | null | 2013-01-01T00:01:00 | true | [CH3:1][N:2](C=O)C.C1COCC1.CN(C)[CH2:13][C:14]1[C:22]2[C:17](=[CH:18][C:19]([N+:23]([O-:25])=[O:24])=[CH:20][CH:21]=2)[NH:16][CH:15]=1.[C-]#N.[K+]>O>[N+:23]([C:19]1[CH:18]=[C:17]2[C:22]([C:14]([CH2:13][C:1]#[N:2])=[CH:15][NH:16]2)=[CH:21][CH:20]=1)([O-:25])=[O:24] | CN(C)Cc1c[nH]c2cc([N+](=O)[O-])ccc12 | CN(C)C=O | null | [C-]#N | [K+] | 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 | 25 | null | To a mixture of DMF (35 mL) and Mel (74.6 g, 0.53 mol) in water (35 mL) and THF (400 mL) was added dimethyl-(6-nitro-1H-indol-3-ylmethyl)-amine (23 g, 0.105 mol). After the reaction mixture was refluxed for 10 min, potassium cyanide (54.6 g, 0.84 mol) was added and the mixture was kept refluxing overnight. The mixture was then cooled to room temperature and filtered. The filtrate was washed with brine (300 mL×3), dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography to give (6-nitro-1H-indol-3-yl)-acetonitrile (B-9-a) (7.5 g, 36%). | N#CCc1c[nH]c2cc([N+](=O)[O-])ccc12 | null | 36 | null |
799,690 | ord_dataset-56a22bc0c3b14f87b9aa3f2fc6488ee7 | null | 2007-01-01T00:12:00 | true | Cl[C:2]([O:4][CH3:5])=[O:3].[CH2:6]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2([C:19]([O:21]C(C)(C)C)=[O:20])[CH2:18][CH2:17]2)=[CH:12][CH:11]=1)[CH:7]=[CH2:8].C(N(CC)CC)C.C(#N)C>>[CH2:6]([N:9]([C:2]([O:4][CH3:5])=[O:3])[C:10]1[CH:15]=[CH:14][C:13]([C:16]2([C:19]([OH:21])=[O:20])[CH2:17][CH2:18]2)=[CH:12][CH:11]=1)[CH:7]=[CH2:8] | COC(=O)Cl | C=CCNc1ccc(C2(C(=O)OC(C)(C)C)CC2)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC#N | CCN(CC)CC | null | null | null | null | null | null | null | null | null | 25 | 0.5 | Methyl chloroformate (34 μL, 0.00044 mol) was added to a mixture of tert-butyl 1-[4-(allylamino)phenyl]cyclopropanecarboxylate (6.0×10−1 mg, 0.00022 mol) and triethylamine (92 μL, 0.00066 mol) in acetonitrile (1.0 mL, 0.019 mol) at rt. The reaction mixture was stirred at rt for 30 minutes, then was washed with water, and then extracted with EtOAc (3×). The organic layers were combined and concentrated. To the residue was added 4.0M HCl in dioxane and the reaction was stirred at rt for 2 h. The solvent was removed in-vacuo and used in the following step. LC/MS: 276.2 (M+H+). | C=CCN(C(=O)OC)c1ccc(C2(C(=O)O)CC2)cc1 | null | null | null |
1,741,378 | ord_dataset-eacfee6d16d8455a93348409f1b37be4 | null | 2016-01-01T00:06:00 | true | [CH2:1]([N:3]([CH:26]1[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1)[C:4]1[CH:5]=[C:6]([CH:15]2[CH2:18][N:17]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:16]2)[CH:7]=[C:8]([C:11]([O:13]C)=[O:12])[C:9]=1[CH3:10])[CH3:2].[OH-].[Na+]>C1COCC1.CO>[C:22]([O:21][C:19]([N:17]1[CH2:18][CH:15]([C:6]2[CH:5]=[C:4]([N:3]([CH2:1][CH3:2])[CH:26]3[CH2:27][CH2:28][O:29][CH2:30][CH2:31]3)[C:9]([CH3:10])=[C:8]([CH:7]=2)[C:11]([OH:13])=[O:12])[CH2:16]1)=[O:20])([CH3:24])([CH3:25])[CH3:23] | CCN(c1cc(C2CN(C(=O)OC(C)(C)C)C2)cc(C(=O)OC)c1C)C1CCOCC1 | null | null | [Na+] | [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 | 16 | To a stirred solution of tert-butyl 3-{3-[ethyl(oxan-4-yl)amino]-5-(methoxycarbonyl)-4-methylphenyl}azetidine-1-carboxylate (78 mg, 0.18 mmol) in THF (2 ml) and MeOH (0.1 ml) was added 2M NaOH solution (0.9 ml, 1.8 mmol) and the reaction was stirred at room temperature for 16 h followed by heating at 50° C. for 22 h. The reaction was cooled to room temperature and the solvent removed in vacuo after which the aqueous solution was adjusted to pH5 using 1M HCl. The product was extracted into DCM (2×50 ml), dried with Na2SO4 and filtered to afford the title compound as a colourless oil (54 mg, 72%). LC-MS 100%, 1.70 min (3.5 minute LC-MS method), m/z=419.2, 1H NMR (500 MHz, MeOD) δ 7.77 (s, 1H), 7.55 (s, 1H), 4.36 (t, J=8.2 Hz, 2H), 3.90 (d, J=27.0 Hz, 5H), 3.71 (t, J=6.5 Hz, 1H), 3.36 (t, J=11.3 Hz, 3H), 2.55 (s, 3H), 1.92-1.81 (m, 1H), 1.64 (d, J=55.8 Hz, 3H), 1.49-1.42 (m, 10H), 0.93 (s, 3H). | CCN(c1cc(C2CN(C(=O)OC(C)(C)C)C2)cc(C(=O)O)c1C)C1CCOCC1 | null | 71.7 | null |
124,162 | ord_dataset-d6752864fa634eb3b05f7440b4fb9a70 | null | 1984-01-01T00:11:00 | true | [C:1]1([O:7][CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.FC(F)(F)C1C=C([C:17]23[CH2:26][CH:21]([O:22][C:23]2([CH3:25])[CH3:24])[N:20]([CH3:27])[CH2:19][CH2:18]3)C=CC=1>CC(C)=O>[CH3:8][O:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:17]1([C:23]([CH3:25])([CH3:24])[OH:22])[CH2:26][CH2:21][N:20]([CH3:27])[CH2:19][CH2:18]1 | CN1CCC2(c3cccc(C(F)(F)F)c3)CC1OC2(C)C | COc1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(C)=O | null | null | null | null | null | null | null | null | null | null | null | null | 4-(2'-Methoxyphenyl)-α,α,1-trimethyl-4-piperidinemethanol was prepared from anisole by the procedure described in Example 3 except that acetone was used in place of cyclopentanone in the preparation of III; m.p. 110°-111°; NMR (in CDCl3): τ2.6-3.1 (m, 4H); 6.2 (s, 3H); 6.7-8.5 (m, 9H); 7.9 (s, 3H) and 8.9 (broad s, 6H). Anal. Calcd. for C16H25NO2 : C, 72.96; H, 9.57; N, 5.32. Found: C, 73.02; H, 9.56; N, 5.41. | COc1ccccc1C1(C(C)(C)O)CCN(C)CC1 | null | null | null |
1,421,922 | ord_dataset-f8e6e6a2d2bf4135b9e346456c81700f | null | 2014-01-01T00:04:00 | true | [F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6](B1OC(C)(C)C(C)(C)O1)=[CH:5]2.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[Cl:29][C:30]1[CH:35]=[C:34]([N:36]([CH2:45][O:46][CH2:47][CH2:48][Si:49]([CH3:52])([CH3:51])[CH3:50])[CH2:37][O:38][CH2:39][CH2:40][Si:41]([CH3:44])([CH3:43])[CH3:42])[N:33]2[N:53]=[CH:54][C:55](I)=[C:32]2[N:31]=1>O1CCOCC1.O>[Cl:29][C:30]1[CH:35]=[C:34]([N:36]([CH2:45][O:46][CH2:47][CH2:48][Si:49]([CH3:52])([CH3:51])[CH3:50])[CH2:37][O:38][CH2:39][CH2:40][Si:41]([CH3:44])([CH3:42])[CH3:43])[N:33]2[N:53]=[CH:54][C:55]([C:6]3[CH:7]=[N:8][C:9]4[C:4]([CH:5]=3)=[CH:3][C:2]([F:1])=[CH:11][CH:10]=4)=[C:32]2[N:31]=1 | C[Si](C)(C)CCOCN(COCC[Si](C)(C)C)c1cc(Cl)nc2c(I)cnn12 | CC1(C)OB(c2cnc3ccc(F)cc3c2)OC1(C)C | null | O=P([O-])([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | C1COCCO1 | null | null | null | null | null | null | null | null | null | 80 | 8 | 6-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoline (3.65 mmol, 996.4 mg), K3PO4 (9.12 mmol, 1933.6 mg), and PdCl2(dppf)CH2Cl2 (0.30 mmol, 248 mg) was added to a solution of 5-chloro-3-iodo-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine (3.04 mmol, 1684.3 mg) in dioxane (18 mL) and H2O (3 mL). The resulting solution was stirred at 80° C. under argon overnight. The mixture was diluted with H2O and then extracted with ethyl acetate (×2). The combined organic layers were washed with brine and dried with Na2SO4. Evaporation and purification by column chromatography afforded 5-chloro-3-(6-fluoroquinolin-3-yl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine: LCMS tR=3.36 Min (5 min run, UV254nm). Mass calculated for, M+ 581.2, observed LC/MS m/z 582.2 (M+H). | C[Si](C)(C)CCOCN(COCC[Si](C)(C)C)c1cc(Cl)nc2c(-c3cnc4ccc(F)cc4c3)cnn12 | null | null | null |
379,125 | ord_dataset-846d411edee44814931e062174d7ef12 | null | 1997-01-01T00:09:00 | true | [C:1]1([NH:7][C:8](=[O:17])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[S:15][CH3:16])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(=O)(O)[O-:19].[K+].BrBr>C1(C)C=CC=CC=1>[C:1]1([NH:7][C:8](=[O:17])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[S:15]([CH3:16])=[O:19])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1 | O=C([O-])O | CSc1ccccc1C(=O)Nc1ccccc1 | null | BrBr | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Cc1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | null | To a 1000 ml four-necked flask equipped with a stirrer, a thermometer, and a condenser, 48.6 g (0.2 mol) of N-phenyl-2-(methylthio)benzamide obtained in Example 1, 300 g of toluene, and 200 g of a 10% by weight aqueous solution of potassium bicarbonate are placed. To the above mixture in the flask, 32.0 g (0.2 mol) of bromine is added dropwise while stirring at a temperature of from 10° to 15° C. to be allowed to react with each other for about 10 minutes. After completion of the reaction, the produced white crystals are filtered and then recrystallized from a mixture of water and ethanol (1:9) to give 48.7 g of N-phenyl-2-(methylsulfinyl)benzamide (melting point: 194° to 195° C.). The yield of the product against N-phenyl-2-(methylthio)benzamide is 94%. | CS(=O)c1ccccc1C(=O)Nc1ccccc1 | null | null | null |
639,767 | ord_dataset-1c0bae7388cf460091d56129e95b3145 | null | 2004-01-01T00:06:00 | true | [CH3:1][CH:2]1[NH:7][CH2:6][C:5]2[S:8][C:9]([C:11]([O-:13])=O)=[N:10][C:4]=2[CH2:3]1.[Li+].[Cl:15][C:16]1[CH:17]=[C:18]2[C:23](=[CH:24][CH:25]=1)[CH:22]=[C:21]([S:26]([N:29]1[CH2:34][CH2:33][NH:32][CH:31]([CH2:35][C:36]([O:38][CH3:39])=[O:37])[CH2:30]1)(=[O:28])=[O:27])[CH:20]=[CH:19]2>>[Cl:15][C:16]1[CH:17]=[C:18]2[C:23](=[CH:24][CH:25]=1)[CH:22]=[C:21]([S:26]([N:29]1[CH2:34][CH2:33][N:32]([C:11]([C:9]3[S:8][C:5]4[CH2:6][NH:7][CH:2]([CH3:1])[CH2:3][C:4]=4[N:10]=3)=[O:13])[CH:31]([CH2:35][C:36]([O:38][CH3:39])=[O:37])[CH2:30]1)(=[O:27])=[O:28])[CH:20]=[CH:19]2 | COC(=O)CC1CN(S(=O)(=O)c2ccc3cc(Cl)ccc3c2)CCN1 | CC1Cc2nc(C(=O)[O-])sc2CN1 | null | [Li+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Starting materials: lithium 6-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxylate, 1-[(6-chloronaphthalen-2-yl)sulfonyl]-3-[methoxycarbonylmethyl]piperazine | COC(=O)CC1CN(S(=O)(=O)c2ccc3cc(Cl)ccc3c2)CCN1C(=O)c1nc2c(s1)CNC(C)C2 | null | null | null |
333,309 | ord_dataset-ba1248d90e3e465693710bbc45866f37 | null | 1996-01-01T00:07:00 | true | Cl[P:2]1[N:5]([C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)[P:4](Cl)[N:3]1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[CH:19]([C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([CH:28]([CH3:30])[CH3:29])[C:23]=1[OH:31])([CH3:21])[CH3:20]>C(N(CC)CC)C>[CH:28]([C:24]1[CH:25]=[CH:26][CH:27]=[C:22]([CH:19]([CH3:21])[CH3:20])[C:23]=1[O:31][P:2]1[N:5]([C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)[P:4]([O:31][C:23]2[C:24]([CH:28]([CH3:29])[CH3:30])=[CH:25][CH:26]=[CH:27][C:22]=2[CH:19]([CH3:21])[CH3:20])[N:3]1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)([CH3:30])[CH3:29] | ClP1N(c2ccccc2)P(Cl)N1c1ccccc1 | CC(C)c1cccc(C(C)C)c1O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(CC)CC | null | null | null | null | null | null | null | null | null | null | null | null | The procedure of Example 1 is repeated using 2,4-dichloro-1,3-diphenyl-1,3,2,4-diazadiphosphetidine, 2,6-diisopropylphenol and triethylamine to give the title compound. | CC(C)c1cccc(C(C)C)c1OP1N(c2ccccc2)P(Oc2c(C(C)C)cccc2C(C)C)N1c1ccccc1 | null | null | null |
1,516,487 | ord_dataset-8c74302143c04eb9983e4b3a7ead2d72 | null | 2014-01-01T00:12:00 | true | [Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:15]4[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=4[Cl:22])[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([CH:23]([CH2:30][CH3:31])[CH:24]([OH:29])[C:25]([F:28])([F:27])[F:26])=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(#N)C>[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:15]4[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=4[Cl:22])[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([CH:23]([CH2:30][CH3:31])[C:24](=[O:29])[C:25]([F:26])([F:27])[F:28])=[CH:4][CH:3]=1 | CCC(c1ccc(Cl)c2nc3n(c12)CCCN3c1ccc(Cl)cc1Cl)C(O)C(F)(F)F | null | null | CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC#N | null | null | null | null | null | null | null | null | null | null | null | 1 | To a stirred solution of 3-[9-chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]-1,1,1-trifluoropentan-2-ol (47.4 mg, 0.0961 mmol) in acetonitrile (0.6 mL) was added Dess-Martin reagent (48.9 mg, 0.115 mmol) at room temperature. After 1 h, the reaction mixture was concentrated in vacuo and purified by flash column chromatography on NH silica gel eluting with a 0-10% methanol/ethyl acetate gradient mixture to give the title compound as a colorless amorphous (33.3 mg, 0.0678 mmol, 71%). | CCC(C(=O)C(F)(F)F)c1ccc(Cl)c2nc3n(c12)CCCN3c1ccc(Cl)cc1Cl | null | null | null |
967,622 | ord_dataset-03ba810b7f464a06b5d8787af2e8b64e | null | 2010-01-01T00:06:00 | true | [CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[SH:9].[Br:10][C:11]1[CH:16]=[C:15]([C:17]([F:20])([F:19])[F:18])[CH:14]=[CH:13][C:12]=1I>>[Br:10][C:11]1[CH:16]=[C:15]([C:17]([F:18])([F:19])[F:20])[CH:14]=[CH:13][C:12]=1[S:9][C:3]1[CH:4]=[CH:5][C:6]([CH3:8])=[CH:7][C:2]=1[CH3:1] | FC(F)(F)c1ccc(I)c(Br)c1 | Cc1ccc(S)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 | Prepared from 2,4-dimethyl-benzenethiol and 2-bromo-1-iodo-4-trifluoromethyl-benzene. | Cc1ccc(Sc2ccc(C(F)(F)F)cc2Br)c(C)c1 | null | null | null |
699,755 | ord_dataset-bbd7e53f000345838ad4920a07a169ff | null | 2006-01-01T00:03:00 | true | [C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(Br)(Br)(Br)[Br:16].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(C)=O>C(Cl)Cl>[Br:16][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1 | BrC(Br)(Br)Br | OCCCCCCCc1ccccc1 | null | c1ccc(P(c2ccccc2)c2ccccc2)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOC(C)=O | ClCCl | null | null | null | null | null | null | null | null | null | null | 0.01 | To a solution of 7-phenyl-1-heptanol (29.1 g, 151.3 mmol) in 800 mL CH2Cl2 at room temperature was added CBr4 (60.2 g, 181.6 mmol) then triphenylphosphine (47.6 g, 181.6 mmol). After 30 s, the reaction had turned a light green color. TLC indicated that the reaction was complete at this point. The solvent was removed in vacuo to give a greenish-white semisolid. To this material was added 10% EtOAc: 90% Hexanes and the resulting suspension was filtered through a pad of silica gel washing well with the same solvent system. There yielded 57 g of a colorless oil as the desired bromide and triphenylphosphine oxide. This oil was then flash chromatographed (Hexanes) to yield 38.6 g, 100% of the bromide as a colorless oil. 1H NMR (CDCl3) δ 1.30–1.49 (m, 6H); 1.60 (quintet, J=8.18 Hz, 2H); 2.60 (t, J=8.18 Hz, 2H); 3.39 (t, J=8.18 Hz, 2H); 7.13–7.20 (m, 3H); 7.21–7.31 (m, 2H). | BrCCCCCCCc1ccccc1 | null | 147.6 | null |
725,318 | ord_dataset-0387783899c642a8b7eb4ba379bcdf5d | null | 2006-01-01T00:08:00 | true | [NH2:1][CH2:2][CH:3]([C:9]1([CH3:14])[O:13][CH2:12][CH2:11][O:10]1)[C:4]([O:6][CH2:7][CH3:8])=[O:5].[F:15][C:16]1[CH:26]=[CH:25][C:24]([F:27])=[C:18]2[C:19]([O:21][C:22](=O)[C:17]=12)=[O:20]>>[F:15][C:16]1[CH:26]=[CH:25][C:24]([F:27])=[C:18]2[C:17]=1[C:22](=[O:21])[N:1]([CH2:2][CH:3]([C:9]1([CH3:14])[O:10][CH2:11][CH2:12][O:13]1)[C:4]([O:6][CH2:7][CH3:8])=[O:5])[C:19]2=[O:20] | O=C1OC(=O)c2c(F)ccc(F)c21 | CCOC(=O)C(CN)C1(C)OCCO1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Ethyl 3-(4,7-difluoro-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-2-(2-methyl-[1,3]dioxolan-2-yl)propionate was prepared in the same manner as described in the above example 5 (20) from ethyl 3-amino-2-(2-methyl-[1,3]dioxolan-2-yl)propionate (0.80 g, 3.94 mmol) and 3,6-difluorophthalic anhydride (0.94 g, 4.33 mmol), and the obtained product was identified with the following NMR data. | CCOC(=O)C(CN1C(=O)c2c(F)ccc(F)c2C1=O)C1(C)OCCO1 | null | null | null |
626,850 | ord_dataset-e44331dc51de453ca14b7032593c1958 | null | 2004-01-01T00:02:00 | true | [F:1]C1C=CC(OC)=C(C2C(C(O)=O)=CC([N+]([O-])=O)=CC=2)C=1.C[C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][C:24]=1[C:31]1[C:32]([C:41]([O:43]C)=[O:42])=[CH:33][C:34]([N+:38]([O-:40])=[O:39])=[CH:35][C:36]=1C>>[F:1][C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][C:24]=1[C:31]1[C:32]([C:41]([OH:43])=[O:42])=[CH:33][C:34]([N+:38]([O-:40])=[O:39])=[CH:35][CH:36]=1 | COc1ccc(F)cc1-c1ccc([N+](=O)[O-])cc1C(=O)O | COC(=O)c1cc([N+](=O)[O-])cc(C)c1-c1cc(OC)ccc1C | null | null | null | null | null | null | null | 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 a manner similar to that of 5′-fluoro-2′-methoxy-4-nitro-2-biphenylcarboxylic acid (EXAMPLE 107) from methyl 2′-methyl-5′-methoxy-6-methyl-4-nitro-2-biphenylcarboxylate (0.77 g) to afford 0.73 g (99%) of 2′-fluoro-5′-methoxy-4-nitro-2-biphenylcarboxylic acid as a white solid, which was used in the next step without further purification. | COc1ccc(F)c(-c2ccc([N+](=O)[O-])cc2C(=O)O)c1 | null | 99 | null |
1,081,716 | ord_dataset-afd812677c134591a99f46ce28de2524 | null | 2011-01-01T00:08:00 | true | [N:1]1([C:7]2[CH:8]=[CH:9][C:10]3[N:11]([C:13]([C:16]([F:19])([F:18])[F:17])=[N:14][N:15]=3)[N:12]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[CH:20]([C:22]1[CH:31]=[CH:30][C:25]([O:26][CH2:27][C:28]#[N:29])=[CH:24][CH:23]=1)=O>>[F:19][C:16]([F:17])([F:18])[C:13]1[N:11]2[N:12]=[C:7]([N:1]3[CH2:2][CH2:3][N:4]([CH2:20][C:22]4[CH:31]=[CH:30][C:25]([O:26][CH2:27][C:28]#[N:29])=[CH:24][CH:23]=4)[CH2:5][CH2:6]3)[CH:8]=[CH:9][C:10]2=[N:15][N:14]=1 | N#CCOc1ccc(C=O)cc1 | FC(F)(F)c1nnc2ccc(N3CCNCC3)nn12 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Reductive amination of 6-(piperazin-1-yl)-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazine with 2-(4-formylphenoxy)acetonitrile was carried out according to General Synthetic Method 7. The crude product was purified by hplc using a Waters XBridge Prep C18 OBD column, 5μ silica, 30 mm diameter, 100 mm length eluted with decreasingly polar mixtures of water (containing 0.1% aqueous ammonia) and acetonitrile as eluents to give 2-[4-[[4-[3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperazin-1-yl]methyl]phenoxy]acetonitrile. | N#CCOc1ccc(CN2CCN(c3ccc4nnc(C(F)(F)F)n4n3)CC2)cc1 | null | null | null |
471,482 | ord_dataset-cd531114850e4f239b2a3661044ae672 | null | 2000-01-01T00:08:00 | true | O1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6](=[O:15])[CH:7]=[CH:8][C:9]1[CH:14]=[CH:13][N:12]=[CH:11][CH:10]=1.[C:16](C1CCCCC1)(=O)[CH3:17]>>[CH:2]1([C:6](=[O:15])[CH:7]=[CH:8][C:9]2[CH:14]=[CH:13][N:12]=[CH:11][CH:10]=2)[CH2:17][CH2:16][CH2:5][CH2:4][CH2:3]1 | CC(=O)C1CCCCC1 | O=C(C=Cc1ccncc1)c1ccco1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | 1-(2-Furyl-3-(4-pyridyl)-2-propene-1-one: MS (m/z): 200.0 (M+H)+ ; C12H9NO2 requir. 199.2. 1-Cyclohexyl-3-(4-pyridyl)-2-propene-1-one was prepared in the same way using acetylcyclohexane: MS (m/z): 216.2 (M+H)+ ; C14H17NO requir. 215.3. | O=C(C=Cc1ccncc1)C1CCCCC1 | null | null | null |
1,254,775 | ord_dataset-c544c0c663f54dbea4ddb52ddde7934e | null | 2013-01-01T00:01:00 | true | COC1C=CC(C[N:8](CC2C=CC(OC)=CC=2)[C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]3[C:17]([NH:24][C:25]4[CH:26]=[N:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=4)=[N:18][CH:19]=[C:20]([CH:23]=3)[CH:21]=O)[N:10]=2)=CC=1.[N:44]1[CH:45]=[N:46][N:47]2[CH2:52][CH2:51][NH:50][CH2:49][C:48]=12>>[N:44]1[CH:45]=[N:46][N:47]2[CH2:52][CH2:51][N:50]([CH2:21][C:20]3[CH:23]=[C:16]([C:11]4[N:12]=[C:13]([CH3:15])[N:14]=[C:9]([NH2:8])[N:10]=4)[C:17]([NH:24][C:25]4[CH:26]=[N:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=4)=[N:18][CH:19]=3)[CH2:49][C:48]=12 | c1nc2n(n1)CCNC2 | COc1ccc(CN(Cc2ccc(OC)cc2)c2nc(C)nc(-c3cc(C=O)cnc3Nc3ccc(OC)nc3)n2)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The title compound was synthesized following an analogous procedure to Example 220 using 5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(6-methoxypyridin-3-ylamino)nicotinaldehyde (178 mg, 0.308 mmol) and 5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyrazine (GeneTech, Indianapolis, Ind.) (57.4 mg, 0.462 mmol). 1H NMR (400 MHz, CDCl3) δ 11.70 (s, 1H); 8.78 (d, J=2.54 Hz, 1H); 8.36 (d, J=2.74 Hz, 1H); 8.25 (d, J=2.35 Hz, 1H); 8.10 (dd, J=8.80, 2.74 Hz, 1H); 7.87 (s, 1H); 6.78 (d, J=8.61 Hz, 1H); 5.59 (s, 2H); 4.20 (t, J=5.38 Hz, 2H); 3.94 (s, 3H); 3.84 (s, 2H); 3.73 (s, 2H); 3.00 (t, J=5.48 Hz, 2H); 2.56 (s, 3H). m/z (ESI, +ve ion) 445.9 (M+H)+. | COc1ccc(Nc2ncc(CN3CCn4ncnc4C3)cc2-c2nc(C)nc(N)n2)cn1 | null | null | null |
1,462,825 | ord_dataset-fd1fa959d6264608b0b7fcda16741bfd | null | 2014-01-01T00:08:00 | true | [Cl:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12](/[CH:16]=[C:17]4/[C:18](=[O:28])[N:19]([C@H:23]5[CH2:27][CH2:26][NH:25][CH2:24]5)[C:20](=[O:22])[S:21]/4)=[CH:13][CH:14]=3)[CH:9]=[N:8]2)=[C:4]([C:31]([F:34])([F:33])[F:32])[CH:3]=1.[CH2:35](I)[CH3:36]>>[Cl:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12](/[CH:16]=[C:17]4/[C:18](=[O:28])[N:19]([C@H:23]5[CH2:27][CH2:26][N:25]([CH2:35][CH3:36])[CH2:24]5)[C:20](=[O:22])[S:21]/4)=[CH:13][CH:14]=3)[CH:9]=[N:8]2)=[C:4]([C:31]([F:34])([F:33])[F:32])[CH:3]=1 | O=C1S/C(=C\c2ccc3c(cnn3Cc3ccc(Cl)cc3C(F)(F)F)c2)C(=O)N1[C@H]1CCNC1 | CCI | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | (5Z)-5-({1-[4-Chloro-2-(trifluoromethyl)benzyl]-1H-indazol-5-yl}methylidene)-3-[(3S)-1-ethylpyrrolidin-3-yl]-1,3-thiazolidine-2,4-dione was prepared from (5Z)-5-({1-[4-chloro-2-(trifluoromethyl)benzyl]-1H-indazol-5-yl}methylidene)-3-[(3S)-pyrrolidin-3-yl]-1,3-thiazolidine-2,4-dione (Example 114) and ethyl iodide at rt following General Procedure S. | CCN1CC[C@H](N2C(=O)S/C(=C\c3ccc4c(cnn4Cc4ccc(Cl)cc4C(F)(F)F)c3)C2=O)C1 | null | null | null |
1,478,577 | ord_dataset-c3c1091f873b4f40827973a6f1f9b685 | null | 2014-01-01T00:09:00 | true | [C:1]([C:3]1[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[CH:5][CH:4]=1)#[N:2].[CH2:13]([Mg]Br)[CH3:14].B(F)(F)F.CCOCC.Cl>C(OCC)C.[Ti+4]>[NH2:2][C:1]1([C:3]2[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[CH:5][CH:4]=2)[CH2:14][CH2:13]1 | CC[Mg]Br | COC(=O)c1ccc(C#N)cc1 | null | [Ti+4] | Cl | FB(F)F | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOCC | null | null | null | null | null | null | null | null | null | null | null | 1 | To the solution of methyl 4-cyanobenzoate (100 g, 620 mmol) in diethyl ether (3 L) was added titanium (IV) isospropoxide (194 g, 682 mmol), followed by dropwise addition of ethylmagnesium bromide 3M solution in diethylether (450 ml, 1.36 mol) at −70° C. The mixture was stirred for 1 h, and then boron trifluoride etherate (157 ml, 1.24 mol) was added at once. After 2 hours, aqueous HCl (5%) was added until the pH showed acidy, then the mixture was filtered. The solid was washed with ethylacetate. The aqueous phase was separated and the organic layer was washed with water. All aqueous layers were collected together, basified with 1M NaOH and extracted with ethylacetate. The organic layer was dried (Na2SO4) and concentrated to afford the title compound (D6) (32.0 g). | COC(=O)c1ccc(C2(N)CC2)cc1 | null | null | null |
825,378 | ord_dataset-0ca5627a13c049a99463095023b09fe5 | null | 2008-01-01T00:06:00 | true | [NH2:1][CH2:2][C:3]1[N:4]=[C:5]([NH:8][C:9]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][C:13]=2[C:19]([CH:21]2[CH2:25][CH2:24][CH2:23][CH2:22]2)=[O:20])=[O:10])[S:6][CH:7]=1.[CH3:26][N:27]([CH3:32])[S:28](Cl)(=[O:30])=[O:29]>>[CH:21]1([C:19]([C:13]2[CH:14]=[C:15]([CH3:18])[CH:16]=[CH:17][C:12]=2[NH:11][C:9](=[O:10])[NH:8][C:5]2[S:6][CH:7]=[C:3]([CH2:2][NH:1][S:28]([N:27]([CH3:32])[CH3:26])(=[O:30])=[O:29])[N:4]=2)=[O:20])[CH2:25][CH2:24][CH2:23][CH2:22]1 | CN(C)S(=O)(=O)Cl | Cc1ccc(NC(=O)Nc2nc(CN)cs2)c(C(=O)C2CCCC2)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 | N-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl)-N′,N′-dimethylsulfamide (104 mg, 89%) was prepared from 1-(4-aminomethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea (90 mg, 0.25 mmol) and dimethylsulfamoyl chloride (0.06 mL, 0.5 mmol) following the general procedure T. | Cc1ccc(NC(=O)Nc2nc(CNS(=O)(=O)N(C)C)cs2)c(C(=O)C2CCCC2)c1 | null | 89.3 | null |
172,217 | ord_dataset-7860c6f563014da8948ede63b7110bde | null | 1988-01-01T00:05:00 | true | [CH3:1][C:2]1[NH:6][C:5]([C:7]2[CH:12]=[CH:11][C:10]([CH3:13])=[CH:9][CH:8]=2)=[N:4][C:3]=1[C:14]([O:16]CC)=O.[NH2:19][NH2:20]>O>[CH3:1][C:2]1[NH:6][C:5]([C:7]2[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][CH:12]=2)=[N:4][C:3]=1[C:14]([NH:19][NH2:20])=[O:16] | CCOC(=O)c1nc(-c2ccc(C)cc2)[nH]c1C | NN | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | null | null | null | null | null | null | null | null | null | null | null | null | A mixture of 4.9 g of the above ester and 15 ml of anhydrous hydrazine was stirred and refluxed overnight. Water was added, the mixture was evaporated and the residue recrystallized from ethanol, giving 3.45 g of 5-methyl-2-(4-methylphenyl)-1H-imidazole-4-carboxylic acid, hydrazide. | Cc1ccc(-c2nc(C(=O)NN)c(C)[nH]2)cc1 | null | null | null |
1,523,564 | ord_dataset-8c74302143c04eb9983e4b3a7ead2d72 | null | 2014-01-01T00:12:00 | true | [Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH:10]=O)=[N:6][C:7]=1[O:8][CH3:9].[NH2:12][CH3:13].[BH4-].[Na+]>C1COCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:10][NH:12][CH3:13])=[N:6][C:7]=1[O:8][CH3:9] | CN | COc1nc(C=O)ccc1Br | null | [BH4-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | 25 | 0.75 | 5-Bromo-6-methoxypicolinaldehyde of preparation 78 (69 mg, 0.32 mmol) in a solution of NH2CH3 in THF (2M, 3 mL) was stirred under nitrogen at room temperature for 45 mins, and LCMS showed a mass of 230 which indicated the presence of the iminium ion. Sodium borohydride (36.2 mg, 0.957 mmol) was added, and the reaction was stirred at room temperature overnight. The desired product was detected by LCMS, and the reaction was quenched with MeOH (0.5 mL) and water (10 ml), then partitioned with EtOAc (10 mL). The organic layer was dried over sodium sulfate, filtered and evaporated to give the title compound as a yellow oil (47 mg), which was taken into the next step without further purification. | CNCc1ccc(Br)c(OC)n1 | null | null | null |
395,439 | ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a | null | 1998-01-01T00:03:00 | true | [I:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[CH3:11])[C:5](O)=[O:6].S(Cl)(C1C=CC(C)=CC=1)(=O)=O.Cl.[CH3:24][NH2:25]>>[CH3:24][NH:25][C:5]([C:4]1[CH:8]=[CH:9][C:10]([CH3:11])=[C:2]([I:1])[CH:3]=1)=[O:6] | CN | Cc1ccc(C(=O)O)cc1I | null | Cc1ccc(S(=O)(=O)Cl)cc1 | 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 | 5 | A solution of 1.0 mmol of 3-iodo-4-methylbenzoic acid, 1.2 mmol of TsCl, and 25 mmol of Py was stirred for 3 h and then 5 mmol of methylamine hydrochloride was added and stirring continued for 5 h. Chromatography provided N-methyl-(3-iodo-4-methylphenyl)carboxamide. | CNC(=O)c1ccc(C)c(I)c1 | null | null | null |
1,663,953 | ord_dataset-42cd9bc5aae3485f9a58f1527bd3abf0 | null | 2015-01-01T00:11:00 | true | [CH2:1]([NH:8][C:9]([NH:11][N:12]([CH2:14][C:15]([OH:17])=O)[CH3:13])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:18][C@H:19]([C:28]([N:30]([C@@H:42]([CH3:50])[CH:43]([O:47][CH2:48][CH3:49])[O:44][CH2:45][CH3:46])[CH2:31][C:32]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH:35]=[CH:34][CH:33]=1)=[O:29])[CH2:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22]>>[CH2:1]([NH:8][C:9]([NH:11][N:12]([CH2:14][C:15]([NH:18][C@H:19]([C:28]([N:30]([C@@H:42]([CH3:50])[CH:43]([O:47][CH2:48][CH3:49])[O:44][CH2:45][CH3:46])[CH2:31][C:32]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH:35]=[CH:34][CH:33]=1)=[O:29])[CH2:20][C:21]([O:23][C:24]([CH3:27])([CH3:25])[CH3:26])=[O:22])=[O:17])[CH3:13])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1 | CCOC(OCC)[C@H](C)N(Cc1cccc2ccccc12)C(=O)[C@@H](N)CC(=O)OC(C)(C)C | CN(CC(=O)O)NC(=O)NCc1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | According to the procedure described in the synthesis method of Compound II-15, 2-(2-(benzylcarbamoyl)-1-methylhydrazinyl)acetic acid (Compound VI-3) 78 mg (0.33 mmol) was coupled with (S)-tert-butyl 3-amino-4-(((S)-1,1-diethoxypropan-2-yl)-(naphthalen-1-ylmethyl)amino)-4-oxobutanoate (Compound IV-16) 100 mg (0.22 mmol) to obtain the title compound. | CCOC(OCC)[C@H](C)N(Cc1cccc2ccccc12)C(=O)[C@H](CC(=O)OC(C)(C)C)NC(=O)CN(C)NC(=O)NCc1ccccc1 | null | null | null |
56,284 | ord_dataset-159c363342e44b539e7a5975c873e30d | null | 1979-01-01T00:05:00 | true | [Cl:1][CH2:2][CH2:3][N:4]([N:17]=[O:18])[C:5](=O)[O:6]C1C=CC=CC=1[N+]([O-])=O.[NH2:19][C@@H:20]1[O:28][C@H:27]([CH2:29][OH:30])[C@@H:25]([OH:26])[C@H:23]([OH:24])[C@H:21]1[OH:22]>CN(C)C=O.C(O)C>[C@@H:20]1([NH:19][C:5](=[O:6])[N:4]([CH2:3][CH2:2][Cl:1])[N:17]=[O:18])[O:28][C@H:27]([CH2:29][OH:30])[C@@H:25]([OH:26])[C@H:23]([OH:24])[C@H:21]1[OH:22] | N[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O | O=NN(CCCl)C(=O)Oc1ccccc1[N+](=O)[O-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | CCO | null | null | null | null | null | null | null | null | null | null | 0.17 | 3.28 g (12 mmol) of o-nitrophenyl N-(2-chloroethyl)-N-nitrosocarbamate is dissolved in a mixture of 10 ml anhydrous dimethylformamide and 10 ml anhydrous ethanol, and to this solution is added little by little 1.79 g (10 mmol) of 1-amino-1-deoxy-β-D-glucopyranose powder, while stirring, at 5°-10° C. over 10 minutes. The resultant mixture is, after adding 5 ml of anhydrous dimethylformamide thereto, stirred further at 10° C. for 5 hours, and the thus reacted solution is concentrated at 40° C. and below, under reduced pressure. The crystalline residue obtained is washed with anhydrous ethyl ether and then with acetone, dried under reduced pressure, and recrystallized from anhydrous ethanol-ethyl ether (1:5) to give 2.47 g of 3-(β-D-glucopyranosyl)-1-(2-chloroethyl)-1-nitrosourea. Yield 78.7%. mp 77°-78° C. (decomp.). [α]D25 -10.3° (C 1.0, water). Analysis for C9H16N3O7Cl (MW 313.69): | O=NN(CCCl)C(=O)N[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O | null | 78.7 | null |
176,514 | ord_dataset-07db50a3ce6941919df30a9e2898988f | null | 1988-01-01T00:08:00 | true | [Cl:1][CH2:2][O:3][C:4](F)(F)[CH:5]([C:10]([F:13])([F:12])[F:11])[C:6]([F:9])([F:8])[F:7].[Si](=O)=[O:17].S(=O)(=O)(O)O>>[F:7][C:6]([F:9])([F:8])[CH:5]([C:10]([F:13])([F:12])[F:11])[C:4]([O:3][CH2:2][Cl:1])=[O:17] | FC(F)(F)C(C(F)(F)F)C(F)(F)OCCl | O=[Si]=O | null | O=S(=O)(O)O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | 21 | In a four necked 1 liter flask equipped with a thermometer, a condenser and a stirrer, 1-chloromethoxy-1,1-difluoro-2-trifluoromethyl-3,3,3-trifluoropropane (276.6 g, 1.04 mol) and silicon dioxide (50.8 g, 0.85 mol) were charged, and concentrated sulfuric acid (60 g, 0.61 mol) was dropwise added thereto while stirring. The reaction was continued at 110° C. for 21 hours. Then, the reaction mixture was distilled to give monochloromethyl 2-trifluoromethyl-3,3,3-trifluoropropanoate (192.9 g). | O=C(OCCl)C(C(F)(F)F)C(F)(F)F | null | 92.8 | null |
1,241,171 | ord_dataset-c544c0c663f54dbea4ddb52ddde7934e | null | 2013-01-01T00:01:00 | true | C(OC([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:22]=[C:23]([C:27]4[CH:32]=[C:31]([NH2:33])[N:30]=[C:29]([C:34]5[CH:39]=[CH:38][CH:37]=[CH:36][N:35]=5)[CH:28]=4)[CH:24]=[N:25][CH:26]=3)=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[N:11]1([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:22]=[C:23]([C:27]4[CH:32]=[C:31]([NH2:33])[N:30]=[C:29]([C:34]5[CH:39]=[CH:38][CH:37]=[CH:36][N:35]=5)[CH:28]=4)[CH:24]=[N:25][CH:26]=3)=[CH:17][CH:16]=2)[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]1 | CC(C)(C)OC(=O)N1CCN(Cc2ccc(-c3cncc(-c4cc(N)nc(-c5ccccn5)c4)c3)cc2)CC1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O=C(O)C(F)(F)F | ClCCl | null | null | null | null | null | null | null | null | null | 25 | 0.5 | To a solution of 4-[4-(6′-Amino-[2,2′;4′,3″]terpyridin-5″-yl)-benzyl]-piperazine-1-carboxylic acid tert-butyl ester (1.0 eq, 0.105 mmol, 55.1 mg) in DCM (1.0 ml) is added TFA (24.0 eq, 2.60 mmol, 0.2 ml). The reaction mixture is allowed to stir at room temperature for 30 minutes. The organic solvent is reduced in vacuo. The residue is purified by reverse phase chromatography (Isolute™ C18, 0-20% acetonitrile in water—0.1% TFA). The appropriate fractions by HPLC are combined and concentrated in vacuo. The resulting residue is dissolved in MeOH and loaded onto a SCX-2 cartridge eluting with MeOH and 2M NH3 in MeOH. The methanolic ammonia fractions are combined, concentrated in vacuo and dried under vacuum to afford the title compound; [M+H]+ 423. | Nc1cc(-c2cncc(-c3ccc(CN4CCNCC4)cc3)c2)cc(-c2ccccn2)n1 | null | null | null |
528,580 | ord_dataset-f027aa93238e424fbbf9bad1c7699adc | null | 2001-01-01T00:12:00 | true | [CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][CH2:14][C@@H:15]([C:18]1[CH:23]=[CH:22][C:21]([CH:24]=[C:25]2[S:29][C:28](=[O:30])[NH:27][C:26]2=[O:31])=[CH:20][CH:19]=1)[O:16][CH3:17].[S]>C1COCC1>[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)=[N:4][C:3]=1[CH2:13][CH2:14][CH:15]([C:18]1[CH:23]=[CH:22][C:21]([CH2:24][C@@H:25]2[S:29][C:28](=[O:30])[NH:27][C:26]2=[O:31])=[CH:20][CH:19]=1)[O:16][CH3:17] | CO[C@@H](CCc1nc(-c2ccccc2)oc1C)c1ccc(C=C2SC(=O)NC2=O)cc1 | null | null | [S] | 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 | The title compound of Example 17 (640 mg, 1.5 mmol) was dissolved in THF (50 mL) and hydrogenated in the presence of sulfur-resistant 10% palladium on carbon (640 mg) on a Parr Shaker at 50 PSI for 20 hours. The catalyst was removed via filtration through diatomaceous earth and the filtrate was concentrated in vacuo. The residue was purified on silica gel, eluting with hexane/ethyl acetate (3/1) plus 5% acetic acid, to afford crude material which was further purified by (dissolving the residue in 50 mL of ethyl acetate, washing with water (25 mL), saturated aqueous sodium bicarbonate (25 mL), brine (25 mL) and drying (MgSO4), to afford a colorless gum (229 mg, 35%). 1HNMR (300 MHz, CDCl3): δ2.0 (m, 2H), 2.3 (s, 3H), 2.5 (t, 2H), 3.1 (dd, 1H), 3.2 (s, 3H), 3.5 (dd, 1H), 4.1 (dd, 1H), 4.4 (dd, 1H), 7.2 (m, 4H), 7.4 (m, 3H), 7.9 (m, 2H), 8.1 (bs, 1H, NH). | COC(CCc1nc(-c2ccccc2)oc1C)c1ccc(C[C@@H]2SC(=O)NC2=O)cc1 | null | 35 | null |
1,240,850 | ord_dataset-c544c0c663f54dbea4ddb52ddde7934e | null | 2013-01-01T00:01:00 | true | C([O:3][C:4](=[O:24])[CH2:5][C@H:6]1[O:10][B:9]([OH:11])[C:8]2[CH:12]=[C:13]([O:17][C:18]3[CH:23]=[N:22][CH:21]=[CH:20][N:19]=3)[CH:14]=[C:15]([CH3:16])[C:7]1=2)C.[Li+].[OH-].Cl>CO.O>[OH:11][B:9]1[C:8]2[CH:12]=[C:13]([O:17][C:18]3[CH:23]=[N:22][CH:21]=[CH:20][N:19]=3)[CH:14]=[C:15]([CH3:16])[C:7]=2[C@@H:6]([CH2:5][C:4]([OH:24])=[O:3])[O:10]1 | CCOC(=O)C[C@H]1OB(O)c2cc(Oc3cnccn3)cc(C)c21 | null | null | Cl | [Li+] | [OH-] | 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 | 3 | To a solution of (3R)-[1-hydroxy-4-methyl-6-(pyrazin-2-yloxy)-1,3-dihydro-benzo[c][1,2]-oxaborol-3-yl]-acetic acid ethyl ester (0.90 g, 2.74 mmol, 1st peak) in methanol (15 mL) was added a solution of LiOH (0.328 g, 13.7 mmol) in water (12 mL) at 0° C. The resulting mixture was stirred at room temperature for 3 hours then acidified to pH=2 with dilute hydrochloric acid and extracted with EtOAc (2×30 mL). The organic extracts were washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel flash column chromatography (DCM/MeOH/AcOH=20:1:trace) to give pure product as a white powder after lyophilization (0.681 g, 82.8%). 1HNMR (400 MHz, DMSO-d δ 9.20 (s, 1H), 8.53 (d, J=1.17 Hz, 1H), 8.35 (d, J=2.64 Hz, 1H), 8.19 (dd, J=2.63, 1.46 Hz, 1H), 7.25 (d, J=2.05 Hz, 1H), 7.10 (d, J=1.46 Hz, 1H), 5.51 (dd, J=9.51, 2.20 Hz, 1H), 3.07 (dd, J=15.52, 2.63 Hz, 1H), 2.28 (s, 3H), 2.13 (dd, 1H). MS (ESI) m/z=301 [M+H]+. | Cc1cc(Oc2cnccn2)cc2c1[C@@H](CC(=O)O)OB2O | null | null | null |
852,590 | ord_dataset-faa0236be76c4501841c954527cd1b6c | null | 2008-01-01T00:12:00 | true | [Br:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]([CH:14]=[N:15]O)=[C:12]([CH3:17])[N:11]=[C:10]3[N:18]([CH2:21][CH3:22])[N:19]=[CH:20][C:9]=23)[CH:5]=[N:6][CH:7]=1.C(OC(=O)C)(=O)C>O>[Br:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]([C:14]#[N:15])=[C:12]([CH3:17])[N:11]=[C:10]3[N:18]([CH2:21][CH3:22])[N:19]=[CH:20][C:9]=23)[CH:5]=[N:6][CH:7]=1 | CCn1ncc2c(-c3cncc(Br)c3)c(C=NO)c(C)nc21 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CC(=O)OC(C)=O | null | null | null | null | null | null | null | null | null | 150 | 2 | A mixture of 4-(5-bromo-3-pyridyl)-1-ethyl-6-methyl-1H-pyrazolo[3,4-b]pyridine-5-carbaldehyde oxime (34 mg) and acetic anhydride (1 ml) was stirred at 90° C. for 2 hours and 150° C. for 2 hours. The reaction mixture was diluted with water and extracted with EtOAc. The organic layer was washed with water, brine, dried over anhydrous MgSO4 and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with a mixture of EtOAc and n-hexane (1:2). The crystalline residue was recrystallized from EtOAc and n-hexane to give 4-(5-bromo-3-pyridyl)-1-ethyl-6-methyl-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile (15.5 mg) as a colorless crystal. | CCn1ncc2c(-c3cncc(Br)c3)c(C#N)c(C)nc21 | null | 48 | null |
1,358,804 | ord_dataset-d932d1d683704a8bad3d064bcb197acc | null | 2013-01-01T00:11:00 | true | [Br:1][C:2]1[CH:3]=[C:4]([C@@H:8]([N:10]2[CH2:15][CH2:14][C@@:13]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)([CH2:16][C:17](=[O:19])[CH3:18])[O:12][C:11]2=[O:27])[CH3:9])[CH:5]=[CH:6][CH:7]=1.[CH3:28][Mg+].[Br-]>C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:3]=[C:4]([C@@H:8]([N:10]2[CH2:15][CH2:14][C@@:13]([C:20]3[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=3)([CH2:16][C:17]([OH:19])([CH3:28])[CH3:18])[O:12][C:11]2=[O:27])[CH3:9])[CH:5]=[CH:6][CH:7]=1 | CC(=O)C[C@]1(c2ccc(F)cc2)CCN([C@@H](C)c2cccc(Br)c2)C(=O)O1 | C[Mg+] | null | [Br-] | 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 | 25 | 0.25 | A solution of (S)-3-((S)-1-(3-bromophenyl)ethyl)-6-(4-fluorophenyl)-6-(2-oxopropyl)-1,3-oxazinan-2-one (18.5 mg, 0.043 mmol) in dry toluene (3 mL) was cooled to 0° C. A solution of MeMgBr (3.0M in THF, 45 μL, 3 equiv) was added. After 15 min, the mixture was warmed to rt slowly and stirred 2 h. LC-MS found reaction completed. The reaction was quenched by satd aq NH4Cl solution (2 mL), diluted with EtOAc (10 mL), washed with 1% aq HCl (3 mL), brine (3 mL), and dried over Na2SO4. After filtration and concentration, the residue was purified by preparative HPLC to afford (S)-3-((S)-1-(3-bromophenyl)ethyl)-6-(4-fluorophenyl)-6-(2-hydroxy-2-methylpropyl)-1,3-oxazinan-2-one (8.0 mg, 42%). LC-MS (3 min) tR=1.75 min, m/z=472, 474 (M+Na); 1H NMR (CDCl3) 7.32-7.21 (m, 3H), 7.12-6.98 (m, 4H), 6.89 (m, 1H), 5.65 (q, 1H), 2.89 (m, 1H), 1.50 (d, 3H), 1.15 (d, 6H). | C[C@@H](c1cccc(Br)c1)N1CC[C@](CC(C)(C)O)(c2ccc(F)cc2)OC1=O | null | 42 | null |
1,712,993 | ord_dataset-3f2a531ffbae4b9eb1048afcd7953beb | null | 2016-01-01T00:04:00 | true | [CH3:1][C:2]([O:5][C:6]([NH:8][C@H:9]([C:13]([OH:15])=O)[CH2:10][C:11]#[CH:12])=[O:7])([CH3:4])[CH3:3].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[NH2:37][C@H:38]([C:43]([O:45][CH3:46])=[O:44])[CH2:39][CH:40]([CH3:42])[CH3:41].Cl.C(N(C(C)C)CC)(C)C>CN(C=O)C>[C:2]([O:5][C:6]([NH:8][CH:9]([CH2:10][C:11]#[CH:12])[C:13]([NH:37][CH:38]([CH2:39][CH:40]([CH3:42])[CH3:41])[C:43]([O:45][CH3:46])=[O:44])=[O:15])=[O:7])([CH3:1])([CH3:3])[CH3:4] | C#CC[C@H](NC(=O)OC(C)(C)C)C(=O)O | COC(=O)[C@@H](N)CC(C)C | null | CCN=C=NCCCN(C)C | Cl | On1nnc2ccccc21 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | CCN(C(C)C)C(C)C | null | null | null | null | null | null | null | null | null | 25 | 8 | To a solution of Boc-L-propargylglycine (26.65 g; 125 mmol) in dry DMF (170 mL) was added EDCI (29.23 g; 152.5 mmol) and HOBt (23.5 g; 122.5 mmol), and the reaction mixture was stirred at room temperature for 40 min (solution A). In a separate RB flask, (L) Leu-OMe hydrochloride (22.72 g; 125 mmol) in dry DMF (82 mL) kept at 0° C. was treated with diisopropyl ethyl amine (DIEA) (64.62 g; 500 mmol) and the solution was stirred for 25 min (solution B). Solution B was added to solution A and the reaction mixture was stirred overnight at room temperature. The solvent was removed on the rotary evaporator and the residue was taken up in dichloromethane (DCM) (600 mL) and washed sequentially with saturated sodium bicarbonate (2×200 mL), 5% HCl (2×200 mL) and brine (200 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated, leaving a crude product which was purified using flash chromatography (silica gel; hexane/ethyl acetate 75:25) to give 1 as a white solid (38.12 g; 89% yield); 1H NMR (CDCl3) δ 8.2 (s, 1H), 7.0 (s, 1H), 4.3 (m, 1H), 4.1 (m, 1H), 3.6 (s, 3H), 2.8 (s, 1H), 2.4 (m, 2H), 2.3 (m, 1H), 1.6 (m, 2H), 1.5 (m, 1H), 1.38 (s, 9H), 0.87 (d, 6H). | C#CCC(NC(=O)OC(C)(C)C)C(=O)NC(CC(C)C)C(=O)OC | null | 89.6 | null |
432,417 | ord_dataset-8cbb58558c904b2b85fa7a1b084a0de9 | null | 1999-01-01T00:06:00 | true | [C:1]1(=[O:7])[O:6][C:4](=[O:5])[CH:3]=[CH:2]1.[CH3:8][OH:9]>>[CH3:8][O:9][C:4](=[O:5])/[CH:3]=[CH:2]\[C:1]([OH:6])=[O:7] | O=C1C=CC(=O)O1 | CO | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | 3 | The same procedure as that of process (I) of Example 1 was conducted to obtain a 50% by weight methanol solution of (A1). In the same manner, to a 1 liter flask were added 24.00 g of maleic anhydride and 39.68 g of methanol, and the resulting mixture was stirred under reflux in a water bath kept at 90° C. Thirty minutes after initiation of the stirring, solid components disappeared, 3 hours after, the temperature was lowered to room temperature to obtain a 50% by weight methanol solution of maleic monomethyl ester. | COC(=O)/C=C\C(=O)O | null | null | null |
317,703 | ord_dataset-eb32c2b9cbdf4fc39ce6c9fe0fa11430 | null | 1995-01-01T00:10:00 | true | [Cl:1][C:2]1[C:3](F)=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]([CH:12]1[CH2:14][CH2:13]1)[CH:9]=[C:8]([C:15]([OH:17])=[O:16])[C:7]2=[O:18].[CH:20]12[CH2:27][NH:26][CH2:25][CH:24]1[CH2:23][CH2:22][NH:21]2>CS(C)=O>[CH:20]12[CH2:27][N:26]([C:3]3[C:2]([Cl:1])=[C:11]4[C:6]([C:7](=[O:18])[C:8]([C:15]([OH:17])=[O:16])=[CH:9][N:10]4[CH:12]4[CH2:14][CH2:13]4)=[CH:5][CH:4]=3)[CH2:25][CH:24]1[CH2:23][CH2:22][NH:21]2 | O=C(O)c1cn(C2CC2)c2c(Cl)c(F)ccc2c1=O | C1CC2CNCC2N1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CS(C)=O | null | null | null | null | null | null | null | null | null | null | null | null | 650 mg (2.3 mmol) of 8-chloro-l-cyclopropyl-7-fluoro-1,4 -dihydro-4 -oxo-3 -quinolinecarboxylic acid together with 315 mg (2.8 retool) of 2,7-diazabicyclo[3.3.0]octane and 510 mg (4.6 mmol) of 1,4-diazabicyclo[2.2.21]octane are heated for six hours at 120° C. in 23 ml of dimethyl sulphoxide. All volatile components are removed under a high vacuum, and the residue is stirred thoroughly with acetonitrile and dried at approximately 100° C. | O=C(O)c1cn(C2CC2)c2c(Cl)c(N3CC4CCNC4C3)ccc2c1=O | null | null | null |
583,122 | ord_dataset-60f3171f0342452f8814e7f294e2be8b | null | 2003-01-01T00:02:00 | true | C(N(CC)CC)C.[CH3:8][O:9][C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][C:18]=1[O:19][CH3:20])[C:15](=[O:21])[O:14][CH:13]2[PH2](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[N:41]1[CH:46]=[CH:45][C:44]([CH:47]=O)=[CH:43][CH:42]=1>C(Cl)Cl>[CH3:8][O:9][C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][C:18]=1[O:19][CH3:20])[C:15](=[O:21])[O:14][C:13]2=[CH:47][C:44]1[CH:45]=[CH:46][N:41]=[CH:42][CH:43]=1 | O=Cc1ccncc1 | COc1cc2c(cc1OC)C([PH2](c1ccccc1)(c1ccccc1)c1ccccc1)OC2=O | 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 | Triethylamine (20 ml, 145 mmoles) was dropwise added to a suspension of 5,6-dimethoxy-3-(triphenyl-λ6-phosphanyl)-3H-isobenzofuran-1-one (78 g, 145 mmoles), obtained as described in example 3, and 4-pyridincarboxaldehyde (13 ml, 145 mmoles) in CH2Cl2 (1 l), at room temperature under stirring. After 1.5 hours the mixture was filtered and evaporated and the residue was treated with ethanol under reflux, cooled and filtered. The mother liquors were chromatographed (eluent: 100% CH2Cl2, then with 1% CH3OH) and the residue was brought to dryness and joined to the above filtrate to give 25 g of the title compound. | COc1cc2c(cc1OC)C(=Cc1ccncc1)OC2=O | null | 60.9 | null |
1,326,464 | ord_dataset-cfad8b3f00044bcda60a96b019f09872 | null | 2013-01-01T00:08:00 | true | Cl.[NH2:2][C@@H:3]1[C:11]2[C:6](=[C:7]([C:12]3[S:16][C:15]([C:17]4[CH:18]=[CH:19][C:20]([O:25][CH:26]([CH3:28])[CH3:27])=[C:21]([CH:24]=4)[C:22]#[N:23])=[N:14][N:13]=3)[CH:8]=[CH:9][CH:10]=2)[CH2:5][CH2:4]1.Cl[C:30]([O:32][CH3:33])=[O:31]>C(Cl)Cl>[CH3:33][O:32][C:30](=[O:31])[NH:2][C@@H:3]1[C:11]2[C:6](=[C:7]([C:12]3[S:16][C:15]([C:17]4[CH:18]=[CH:19][C:20]([O:25][CH:26]([CH3:28])[CH3:27])=[C:21]([C:22]#[N:23])[CH:24]=4)=[N:14][N:13]=3)[CH:8]=[CH:9][CH:10]=2)[CH2:5][CH2:4]1 | COC(=O)Cl | CC(C)Oc1ccc(-c2nnc(-c3cccc4c3CC[C@@H]4N)s2)cc1C#N | null | Cl | 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 | Prepared using General Procedure 8. To a stirred solution of (S)-5-(5-(1-amino-2,3-dihydro-1H-inden-4-yl)-1,3,4-thiadiazol-2-yl)-2-isopropoxybenzonitrile hydrochloride 4 (15 mg, 0.03 mmol) and TEA (11 mg, 0.1 mmol) in DCM (1 mL) was added methyl chloroformate (10 mg, 0.1). The reaction mixture was stirred at room temperature for 16 h. The solvent was evaporated and water (2 mL) was added. The resulting solid was filtered, washed with water, and dried under high vacuum to afford 12 mg (92%) of (S)-methyl(4-(5-(3-cyano-4-isopropoxyphenyl)-1,3,4-thiadiazol-2-yl)-2,3-dihydro-1H-inden-1-yl)carbamate 16 as white solid. LCMS-ESI (m/z) calculated for C23H22N4O3S: 434.1; found 435.3 [M+H]+, tR=3.69 min. | COC(=O)N[C@H]1CCc2c(-c3nnc(-c4ccc(OC(C)C)c(C#N)c4)s3)cccc21 | null | 92.1 | null |
1,246,936 | 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]([CH:23]4[CH2:25][CH2:24]4)=[CH:18][N:17]=3)[CH2:12][CH2:11]2)=[O:9])=[C:4]([CH3:26])[CH:3]=1.[O:27]=[C:28]1[NH:32][C@H:31]([CH2:33][O:34]C(=O)C2C=CC=CC=2)[CH2:30][O:29]1>>[CH:23]1([C:19]2[CH:20]=[C:21]([CH3:22])[C:16]([N:13]3[CH2:14][CH2:15][N:10]([C:8]([C:5]4[CH:6]=[CH:7][C:2]([N:32]5[C@H:31]([CH2:33][OH:34])[CH2:30][O:29][C:28]5=[O:27])=[CH:3][C:4]=4[CH3:26])=[O:9])[CH2:11][CH2:12]3)=[N:17][CH:18]=2)[CH2:25][CH2:24]1 | Cc1cc(Br)ccc1C(=O)N1CCN(c2ncc(C3CC3)cc2C)CC1 | O=C1N[C@H](COC(=O)c2ccccc2)CO1 | null | null | null | null | null | null | null | 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 19 and using (4-bromo-2-methylphenyl)[4-(5-cyclopropyl-3-methylpyridin-2-yl)piperazin-1-yl]methanone (347 mg) described in Preparation Example 130 and benzoic acid (R)-2-oxooxazolidin-4-ylmethyl ester (278 mg), the title compound (270 mg) was obtained. | Cc1cc(N2C(=O)OC[C@H]2CO)ccc1C(=O)N1CCN(c2ncc(C3CC3)cc2C)CC1 | null | 71.6 | null |
1,588,360 | ord_dataset-380e279f82154dba9e08ab51b3bdd08a | null | 2015-01-01T00:05:00 | true | C(O)(C(F)(F)F)=O.[C:8]([C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:17]=[N:18][N:19]([C:22]3[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][N:23]=3)[C:20]=2[OH:21])=[C:12]([CH3:31])[CH:11]=1)#[N:9].[CH3:32][N:33]1[CH2:37][CH2:36][CH2:35][CH:34]1[CH2:38][CH2:39][NH2:40]>>[C:8]([C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:17]=[N:18][N:19]([C:22]3[CH:30]=[CH:29][C:25]([C:26]([NH:40][CH2:39][CH2:38][CH:34]4[CH2:35][CH2:36][CH2:37][N:33]4[CH3:32])=[O:27])=[CH:24][N:23]=3)[C:20]=2[OH:21])=[C:12]([CH3:31])[CH:11]=1)#[N:9] | Cc1cc(C#N)ccc1-c1cnn(-c2ccc(C(=O)O)cn2)c1O | CN1CCCC1CCN | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O=C(O)C(F)(F)F | null | null | null | null | null | null | null | null | null | null | null | null | The title compound, as a TFA salt, was prepared in a manner similar to Example 74 using 6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid and 2-(1-methylpyrrolidin-2-yl)ethanamine 1H NMR (400 MHz, DMSO-d6) δ ppm 1.60-1.83 (m, 2H) 1.83-2.08 (m, 2 H) 2.18 (dd, J=12.88, 4.29 Hz, 1 H) 2.27-2.41 (m, 1 H) 2.44 (s, 3 H) 2.84 (d, J=3.54 Hz, 3 H) 3.08 (br. s., 1 H) 3.29 (br. s., 1 H) 3.40 (q, J=6.57 Hz, 2 H) 3.58 (d, J=4.29 Hz, 1 H) 7.67 (d, J=7.58 Hz, 1 H) 7.70-7.89 (m, 2 H) 8.20 (br. s., 1 H) 8.42 (br. s., 1H) 8.50-8.71 (m, 1 H) 8.84 (br. s., 1 H) 8.89-8.95 (m, 1 H) 9.53 (br. s., 1 H) 12.81-13.56 (m, 1 H). MS m/z [M+H]+ 431.2. | Cc1cc(C#N)ccc1-c1cnn(-c2ccc(C(=O)NCCC3CCCN3C)cn2)c1O | null | null | null |
1,187,792 | ord_dataset-9cd817a75dfc4fe7ad19d4232772d5ff | null | 2012-01-01T00:07:00 | true | [CH:1]1([CH:6]=[C:7]([C:17]2[CH:22]=[CH:21][C:20]([C:23]([OH:28])([CH2:26][CH3:27])[CH2:24][CH3:25])=[CH:19][CH:18]=2)[C:8]2[NH:16][C:11]3=[N:12][CH:13]=[CH:14][CH:15]=[C:10]3[CH:9]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1>[Pd].CO>[CH:1]1([CH2:6][CH:7]([C:17]2[CH:18]=[CH:19][C:20]([C:23]([OH:28])([CH2:26][CH3:27])[CH2:24][CH3:25])=[CH:21][CH:22]=2)[C:8]2[NH:16][C:11]3=[N:12][CH:13]=[CH:14][CH:15]=[C:10]3[CH:9]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1 | CCC(O)(CC)c1ccc(C(=CC2CCCC2)c2cc3cccnc3[nH]2)cc1 | null | null | [Pd] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | 50 | null | A mixture of 3-{4-[2-cyclopentyl-1-(1H-pyrrolo[2,3-b]pyridin-2-yl)-vinyl]-phenyl}-pentan-3-ol (120 mg, 0.32 mmol) and 10% palladium on activated carbon (36 mg) in methanol (250 mL) was heated at 50° C. under hydrogen (50 psi) for 16 h. The mixture was cooled to 25° C., the solids filtered off, washed with ethyl acetate and concentrated in vacuo. Purification using a Waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% ammonium hydroxide in water) afforded 3-{4-[2-cyclopentyl-1-(1H-pyrrolo[2,3-b]pyridin-2-yl)-ethyl]-phenyl}-pentan-3-ol (68 mg, 60%): LC/MS m/e calcd for C25H32N2O [M+H]+ 377.55, observed 377.3; 1H NMR (400 MHz, CD3OD) δ ppm 8.04 (d, J=3.8 Hz, 1H), 7.87 (dd, J=7.7, 1.1 Hz, 1H), 7.25-7.34 (m, 4H), 7.02 (dd, J=7.7, 4.9 Hz, 1H), 6.31 (s, 1H), 4.15 (t, J=7.8 Hz, 1H), 2.21 (dt, J=13.7, 7.2 Hz, 1H), 2.03-2.11 (m, 1H), 1.58-1.85 (m, 9H), 1.42-1.54 (m, 2H), 1.14-1.28 (m, 2H), 0.72 (td, J=7.4, 2.1 Hz, 6H). | CCC(O)(CC)c1ccc(C(CC2CCCC2)c2cc3cccnc3[nH]2)cc1 | null | 56.4 | null |
665,003 | ord_dataset-5a3d853c53674888a5691dce2e398792 | null | 2005-01-01T00:03:00 | true | [C:1]([N:4]1[C:13]2[C:12]3=[N:14][C:15]([CH3:17])=[CH:16][N:11]3[CH:10]=[CH:9][C:8]=2[C@@H:7]([O:18][CH2:19][CH2:20][O:21][CH3:22])[C@H:6]([O:23][C:24](=[O:29])[C:25]([CH3:28])([CH3:27])[CH3:26])[C@H:5]1[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)(=[O:3])[CH3:2].C1C(=O)N([Cl:43])C(=O)C1>C(O)C>[C:1]([N:4]1[C:13]2[C:12]3=[N:14][C:15]([CH3:17])=[C:16]([Cl:43])[N:11]3[CH:10]=[CH:9][C:8]=2[C@@H:7]([O:18][CH2:19][CH2:20][O:21][CH3:22])[C@H:6]([O:23][C:24](=[O:29])[C:25]([CH3:26])([CH3:27])[CH3:28])[C@H:5]1[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)(=[O:3])[CH3:2] | O=C1CCC(=O)N1Cl | COCCO[C@@H]1c2ccn3cc(C)nc3c2N(C(C)=O)[C@H](c2ccccc2)[C@H]1OC(=O)C(C)(C)C | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | null | null | null | null | null | null | null | null | null | null | null | 2 | To a of 0° C. cooled solution of 1.00 g (2.10 mmol) (7R,8R,9R)-10-acetyl-7-(2-methoxyethoxy)-2-methyl-9-phenyl-8-pivaloyloxy-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine in ethanol (20 ml) is added 0.28 g (2.10 mmol) NCS and the mixture is stirred for 2 h. Afterwards the reaction is quenched by adding of saturated aqueous sodium hydrogen carbonate solution and is extracted twice with dichloromethane. The combined organic layers are washed with brine, dried over sodium sulphate and evaporated in vacuo. The crude product is purified by column chromatography (ethyl acetate/cylohexane: 1/1) to provide 0.89 g (1.73 mmol/82%) of the title compound as a colourless solid with a melting point of 167-170° C. (cyclohexane). | COCCO[C@@H]1c2ccn3c(Cl)c(C)nc3c2N(C(C)=O)[C@H](c2ccccc2)[C@H]1OC(=O)C(C)(C)C | null | null | null |
1,684,757 | ord_dataset-3953983e052a4076aa7cc0880b79cb8b | null | 2016-01-01T00:01:00 | true | [NH2:1][CH:2]([C:11]1[C:16]([O:17][CH3:18])=[CH:15][N:14]=[CH:13][C:12]=1[O:19][CH3:20])[CH2:3][CH2:4][CH2:5][CH2:6][C:7]([O:9]C)=O.[C:21]1([C:27]2[S:28][CH:29]=[C:30]([CH:32]=O)[N:31]=2)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>>[CH3:20][O:19][C:12]1[CH:13]=[N:14][CH:15]=[C:16]([O:17][CH3:18])[C:11]=1[CH:2]1[N:1]([CH2:32][C:30]2[N:31]=[C:27]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)[S:28][CH:29]=2)[C:7](=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3]1 | COC(=O)CCCCC(N)c1c(OC)cncc1OC | O=Cc1csc(-c2ccccc2)n1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Prepared according to the described general procedure 1 (GP1) by reaction of methyl 6-amino-6-(3,5-dimethoxypyridin-4-yl)hexanoate with commercially available 2-phenylthiazole-4-carbaldehyde. Subsequent purification by preparative HPLC afforded the target compound. LC-MS (conditions A): tR=0.61 min.; [M+H]+: 423.86 g/mol. | COc1cncc(OC)c1C1CCCCC(=O)N1Cc1csc(-c2ccccc2)n1 | null | null | null |
234,844 | ord_dataset-45d20d09e4d64f45bdd419044025b4d3 | null | 1991-01-01T00:09:00 | true | O.[OH-].[Li+].[NH2:4][CH2:5][CH2:6][CH2:7][P:8]([CH:13]([O:18][CH2:19][CH2:20][CH3:21])[O:14][CH2:15][CH2:16][CH3:17])(=[O:12])[O:9]CC>O.C(O)C>[NH2:4][CH2:5][CH2:6][CH2:7][P:8]([CH:13]([O:18][CH2:19][CH2:20][CH3:21])[O:14][CH2:15][CH2:16][CH3:17])(=[O:9])[OH:12] | CCCOC(OCCC)P(=O)(CCCN)OCC | null | null | [Li+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | O | null | null | null | null | null | null | null | null | null | 25 | 120 | To a stirred solution of 0.05 g of lithium hydroxide monohydrate in 7.7 ml of water, is added a solution of 4.37 g of ethyl 3-aminopropyl(di-n-propyloxymethyl)phosphinate in 16.2 ml of ethanol. A slight exothermic reaction ensues and the reaction mixture becomes cloudy.A further 2 ml of water are added and the clear solution stirred at room temperature for 5 days. After: this time the mixture is concentrated in vacuo at 55° and the residue redissolved in water and extracted with 3×10 ml of dichloromethane. The aqueous layer is again evaporated to dryness and the residue dissolved in 20 ml of water and treated with 0.51 ml of 85% phosphoric acid. After stirring overnight, thesolid is removed by filtration. Evaporation of the filtrate and crystallisation of the residue from ethanol/ether affords 3-aminopropyl(di-n-propyloxymethyl) phosphinic acid, m.p. 223°-225°, as a white solid. | CCCOC(OCCC)P(=O)(O)CCCN | null | null | null |
1,159,820 | ord_dataset-b195433d5c354ddfb6cde0d53c41910f | null | 2012-01-01T00:04:00 | true | C[O:2][C:3]([C@@H:5]1[CH2:9][C@@H:8]([S:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)(=[O:12])=[O:11])[CH2:7][N:6]1[C:19]1[N:20]([C:25]2[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][CH:26]=2)[N:21]=[C:22]([CH3:24])[CH:23]=1)=[O:4].[OH-].[Li+]>>[C:13]1([S:10]([C@H:8]2[CH2:7][N:6]([C:19]3[N:20]([C:25]4[CH:30]=[CH:29][C:28]([C:31]([F:33])([F:34])[F:32])=[CH:27][CH:26]=4)[N:21]=[C:22]([CH3:24])[CH:23]=3)[C@H:5]([C:3]([OH:4])=[O:2])[CH2:9]2)(=[O:12])=[O:11])[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1 | COC(=O)[C@@H]1C[C@@H](S(=O)(=O)c2ccccc2)CN1c1cc(C)nn1-c1ccc(C(F)(F)F)cc1 | 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 253e, (2S,4R)-4-benzenesulfonyl-1-[5-methyl-2-(4-trifluoromethyl-phenyl)-2H-pyrazol-3-yl]-pyrrolidine-2-carboxylic acid methyl ester was saponified in the presence of lithium hydroxide to give the title compound as yellow solid. MS (ESI): m/z=480.1 [M+H]+. | Cc1cc(N2C[C@H](S(=O)(=O)c3ccccc3)C[C@H]2C(=O)O)n(-c2ccc(C(F)(F)F)cc2)n1 | null | null | null |
639,650 | ord_dataset-1c0bae7388cf460091d56129e95b3145 | null | 2004-01-01T00:06:00 | true | [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][OH:9])=[C:4]([O:10][CH3:11])[CH:3]=1.CN1CCOCC1>C(Cl)Cl.[Ru]([O-])(=O)(=O)=O.C([N+](CCC)(CCC)CCC)CC>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]=[O:9])=[C:4]([O:10][CH3:11])[CH:3]=1 | COc1cc(Cl)ccc1CO | null | null | O=[Ru](=O)(=O)[O-] | CCC[N+](CCC)(CCC)CCC | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN1CCOCC1 | ClCCl | null | null | null | null | null | null | null | null | null | 25 | 2.5 | In methylene chloride (80 ml) was dissolved (4-chloro-2-methoxyphenyl)methanol (3.69 g). Under ice cooling, molecular sieve 4A (4.57 g), N-methylmorpholine (2.81 g) and tetra-n-propylammonium perruthenate (420 mg) were added to the resulting solution, followed by stirring at room temperature for 2.5 hours. The reaction mixture was distilled under reduced pressure. The residue was subjected to chromatography on a silica gel column (hexane:ethyl acetate=9:1), whereby the title compound (3.07 g) was obtained as pale yellow oil. | COc1cc(Cl)ccc1C=O | null | null | null |
331,375 | ord_dataset-1558660634294cc8ad7e01746e9083fd | null | 1996-01-01T00:06:00 | true | [CH3:1][O:2][C:3]1[C:4]([N+:20]([O-])=O)=[C:5]([C:9]2[O:10][C:11]3[CH:19]=[CH:18][CH:17]=[CH:16][C:12]=3[C:13](=[O:15])[CH:14]=2)[CH:6]=[CH:7][CH:8]=1>CO.C1COCC1.[Ni]>[NH2:20][C:4]1[C:3]([O:2][CH3:1])=[CH:8][CH:7]=[CH:6][C:5]=1[C:9]1[O:10][C:11]2[CH:19]=[CH:18][CH:17]=[CH:16][C:12]=2[C:13](=[O:15])[CH:14]=1 | COc1cccc(-c2cc(=O)c3ccccc3o2)c1[N+](=O)[O-] | null | null | [Ni] | null | 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 | null | null | 2-(3-Methoxy-2-nitrophenyl)-4-oxo-4H-[1]benzopyran (1.73 g, 5.8 mmol) in methanol (50 mL) and THF (50 mL) is hydrogenated under pressure with RaNi (0.5 g). The solution is concentrated under reduced pressure and recrystallized from toluene to yield 2-(2-amino-3-methoxyphenyl)-4-oxo-4H-[1]benzopyran (900 mg, 58%) as a solid. 1H NMR (DMSO): δ8.07 (1H, d, J=8.0 Hz), 7.83 (1H, t, J=6.9 Hz), 7.70 (1H, d, J=7.7 Hz), 7.51 (1H, t, J=7.0 Hz), 7.09 (1H, d, J=8.0 Hz), 7.00 (1H, d, J=7.0 Hz), 6.71 (1H, t, J=8.0 Hz), 6.56 (1H, s), 5.30 (2H, s), 3.85 (3H, s). | COc1cccc(-c2cc(=O)c3ccccc3o2)c1N | null | 58.1 | null |
818,214 | ord_dataset-50f99930fc41474db226bc80774b38df | null | 2008-01-01T00:04:00 | true | [Br:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([CH2:13][C:14]2[S:15][CH:16]=[C:17]([C:19]([O:21]CC)=[O:20])[N:18]=2)[CH3:12])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[OH-].[Li+]>O1CCOCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([CH2:13][C:14]2[S:15][CH:16]=[C:17]([C:19]([OH:21])=[O:20])[N:18]=2)[CH3:12])(=[O:10])=[O:9])=[CH:4][CH:3]=1 | CCOC(=O)c1csc(CN(C)S(=O)(=O)c2ccc(Br)cc2)n1 | null | null | [Li+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1COCCO1 | null | null | null | null | null | null | null | null | null | null | 50 | 72 | Ethyl 2-(N-(4-bromobenzenesulphonyl)-N-methylaminomethyl)thiazole-4-carboxylate (2.19, 5.2 mmol) was added to mixture of 1N lithium hydroxide solution (10 ml, 10 mmol) and dioxan (20 ml) and heated to 50° C. until a solution was obtained. The mixture was stirred at room temperature for a further 3 days. The mixture was evaporated, taken up in EtOAc and acidified with 1N potassium hydrogen sulphate solution. The phases were separated and the organic phase washed with water and brine, dried and reduced to afford 2-(N-(4-bromobenzenesulphonyl)-N-methylaminomethyl)thiazole-4-carboxylic acid (1.86 g, 95%) as a white solid. | CN(Cc1nc(C(=O)O)cs1)S(=O)(=O)c1ccc(Br)cc1 | null | 91.4 | null |
1,713,585 | ord_dataset-3f2a531ffbae4b9eb1048afcd7953beb | null | 2016-01-01T00:04:00 | true | O[C@@:2]([CH3:54])([C:5](=[O:53])[C@@H:6]([NH:11][C:12](=[O:52])[C@@H:13]([NH:21][C:22](=[O:51])[C@@H:23]([N:28](C)[C:29](=[O:49])[C@@H:30]([NH:39][C:40](=[O:48])[CH2:41][N:42]1[CH2:47][CH2:46][O:45][CH2:44][CH2:43]1)[CH2:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[CH2:24][CH:25]([CH3:27])[CH3:26])[CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH2:7][CH:8]([CH3:10])[CH3:9])[CH2:3][I:4].[CH3:55][O:56][C:57]1[CH:71]=[CH:70][C:60]([CH2:61][O:62][C:63](=[O:69])[CH2:64][CH2:65][C:66]([OH:68])=[O:67])=[CH:59][CH:58]=1.C1CCC(N=C=NC2CCCCC2)CC1>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:66]([O:68][C@:2]([CH3:54])([CH2:3][I:4])[C:5](=[O:53])[C@H:6]([CH2:7][CH:8]([CH3:9])[CH3:10])[NH:11][C:12](=[O:52])[C@H:13]([CH2:14][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)[NH:21][C:22](=[O:51])[C@H:23]([CH2:24][CH:25]([CH3:27])[CH3:26])[NH:28][C:29](=[O:49])[C@H:30]([CH2:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[NH:39][C:40](=[O:48])[CH2:41][N:42]1[CH2:43][CH2:44][O:45][CH2:46][CH2:47]1)(=[O:67])[CH2:65][CH2:64][C:63]([O:62][CH2:61][C:60]1[CH:59]=[CH:58][C:57]([O:56][CH3:55])=[CH:71][CH:70]=1)=[O:69] | COc1ccc(COC(=O)CCC(=O)O)cc1 | CC(C)C[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CCc1ccccc1)NC(=O)CN1CCOCC1)C(=O)[C@](C)(O)CI | 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 | 30 | 3 | Referring to FIG. 43, to a solution of compound (S)—N—((S)-1-(((2S,4S)-2-hydroxy-1-iodo-2,6-dimethyl-3-oxoheptan-4-yl)amino)-1-oxo-3-phenylpropan-2-yl)-4-methyl-2-((S)—N-methyl-2-(2-morpholinoacetamido)-4-phenylbutanamido)pentanamide (20, 1.5 g, 1.77 mmol) in DCM (10 mL) were added 4-((4-methoxybenzyl)oxy)-4-oxobutanoic acid (2.1 g, 8.81 mmol), DCC (1.82 g, 8.82 mmol) and DMAP (1.08 g, 8.84 mmol). The reaction mixture was stirred for 3 h at 30° C. (TLC analysis showed very little of 19 was left). The mixture was diluted with DCM (100 mL) and then filtered. The filtrate was washed with saturated citric acid solution (50 mL×2) and saturated NaHCO3 solution (50 mL×3), dried over anhydrous Na2SO4 and concentrated. The residue was purified by flash column chromatography (EtOAc/DCM=1:15 to 2:1) to give product (1.7 g, 90% yield) as a yellow powder. | COc1ccc(COC(=O)CCC(=O)O[C@](C)(CI)C(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCc2ccccc2)NC(=O)CN2CCOCC2)cc1 | null | 89.9 | null |
81,375 | ord_dataset-f196f0a87dd74fcd82ca019f8ff5cf9c | null | 1981-01-01T00:05:00 | true | [OH:1][C:2]1[CH:3]=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([CH:9]=1)[CH:7]=[O:8].[C:13](OC(=O)C)(=[O:15])[CH3:14]>O>[C:13]([O:1][C:2]1[CH:3]=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([CH:9]=1)[CH2:7][OH:8])(=[O:15])[CH3:14] | O=Cc1cc(O)ccc1[N+](=O)[O-] | CC(=O)OC(C)=O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | null | null | null | null | null | null | null | null | null | null | null | null | A mixture of 5-hydroxy-2-nitrobenzaldehyde (4 g.) and acetic anhydride (10 ml.) was heated on a steam bath for 1 hour, then poured into water (100 ml.) and extracted with diethyl ether (3×50 ml.). The extracts were combined and dried, and the solvent was evaporated. The residue of 5-acetoxy-2-nitrobenzaldehyde was dissolved in absolute ethanol (100 ml.), and stirred and ice-cooled while sodium borohydride (1.5 g.) was added in portions. The reaction mixture was stirred at room temperature for 1 hour, then water (100 ml.) was added, and the mixture was extracted with ether (3×70 ml.). The extracts were combined and dried, and the solvent was evaporated to give 5-acetoxy-2-nitrobenzyl alcohol, which was hydrogenated by the general process described in the latter part of Example 13(a) to give the required starting material. | CC(=O)Oc1ccc([N+](=O)[O-])c(CO)c1 | null | null | null |
992,866 | ord_dataset-b6d8835b0c934476a36e6149e7597487 | null | 2010-01-01T00:09:00 | true | [Br:1][C:2]1[NH:3][C:4]2[C:9]([C:10]=1[CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)=[CH:8][CH:7]=[C:6]([C:17]([O:19][CH3:20])=[O:18])[CH:5]=2.[H-].[Na+].[CH3:23][O:24][CH:25]([O:28][CH3:29])[CH2:26]Br>CN(C=O)C>[Br:1][C:2]1[N:3]([CH2:26][CH:25]([O:28][CH3:29])[O:24][CH3:23])[C:4]2[C:9]([C:10]=1[CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)=[CH:8][CH:7]=[C:6]([C:17]([O:19][CH3:20])=[O:18])[CH:5]=2 | COC(=O)c1ccc2c(C3CCCCC3)c(Br)[nH]c2c1 | COC(CBr)OC | 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 | 80 | 1 | To a stirred solution of methyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxylate (prepared as described in published International patent application WO2004/087714) (0.2 M, 1 eq.) in DMF at RT was added NaH (60% dispersion in mineral oil, 1.75 eq). After 1 h, KI (8 mol %) and bromoacetaldehyde dimethyl acetal (2.5 eq) were added and the reaction heated at 80° C. for 17 h. After cooling to RT, the reaction was quenched by addition of aqueous HCl (1N) and extracted into EtOAc (×3). The combined organics were washed with HCl (1N), H2O and brine before being dried (Na2SO4), filtered and concentrated in vacuo. Purification by flash column chromatography (Biotage, 5-10% EtOAc/PE gradient) gave the title compound as a white solid (79%); MS (ES+) m/z 446 (M+H)+, 448 (M+H)+. | COC(=O)c1ccc2c(C3CCCCC3)c(Br)n(CC(OC)OC)c2c1 | null | 79 | null |
1,362,738 | ord_dataset-d932d1d683704a8bad3d064bcb197acc | null | 2013-01-01T00:11:00 | true | [C:1]([C:4]1[CH:11]=[CH:10][C:7]([C:8]#[N:9])=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[CH2:12]([Mg]Cl)[C:13]([CH3:16])([CH3:15])[CH3:14].C(OCC)C>C(OCC)C.C1COCC1>[OH:3][C:1]([C:4]1[CH:11]=[CH:10][C:7]([C:8]#[N:9])=[CH:6][CH:5]=1)([CH3:2])[CH2:12][C:13]([CH3:16])([CH3:15])[CH3:14] | CC(=O)c1ccc(C#N)cc1 | CC(C)(C)C[Mg]Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOCC | C1CCOC1 | null | null | null | null | null | null | null | null | null | 0 | 8 | Dissolve 4-acetylbenzonitrile (1 g, 6.88 mmol) in diethyl ether/THF (1:1, 60 mL) and cool the solution to 0° C. Add 1 M neopentylmagnesium chloride in diethyl ether (8.3 mL, 8.3 mmol) under nitrogen and stir the mixture at room temperature overnight. Add saturated aqueous NH4Cl and extract the mixture twice with EtOAc. Dry the combined organic extracts over MgSO4, filter and concentrate in vacuo. Purify the crude mixture by chromatography on silica gel eluting with hexane and hexane/EtOAc (19:1, 9:1) to give the desired intermediate (364 mg, 24%). | CC(C)(C)CC(C)(O)c1ccc(C#N)cc1 | null | 24 | null |
157,121 | ord_dataset-58ec6779628e43e2b3f0972725f262e6 | null | 1987-01-01T00:05:00 | true | [CH2:1]([N:8]1[C:13](=[O:14])[C:12](=[C:15]2[S:19][CH:18]=[CH:17][S:16]2)[C:11](=[O:20])[CH:10](C(OCC)=O)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+].Cl>C(O)C>[CH2:1]([N:8]1[CH2:9][CH2:10][C:11](=[O:20])[C:12](=[C:15]2[S:16][CH:17]=[CH:18][S:19]2)[C:13]1=[O:14])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1 | CCOC(=O)C1CN(Cc2ccccc2)C(=O)C(=C2SC=CS2)C1=O | null | null | Cl | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | null | null | null | null | null | null | null | null | null | null | null | null | Ethyl 1-benzyl-5-(1,3-dithiol-2-ylidene)-4,6-dioxopiperidine-3-carboxylate (2.0 g) is dissolved in ethanol (160 ml), and a 10% aqueous sodium hydroxide solution (8.0 ml) is added thereto. The mixture is refluxed for 2 hours. The mixture is cooled, neutralized with 10% hydrochloric acid, and then evaporated under reduced pressure to remove the solvent. The residue is dissolved in ethyl acetate, and the solution is washed with water, dried and then evaporated to remove the solvent. The residue thus obtained is recrystallized from isopropanol, whereby 1-benzyl-3-(1,3-dithiol-2-ylidene)-2,4-dioxopiperidine (1.26 g) is obtained as pale yellow needles. Yield: 78%. | O=C1CCN(Cc2ccccc2)C(=O)C1=C1SC=CS1 | null | 78 | null |
1,473,097 | ord_dataset-fd1fa959d6264608b0b7fcda16741bfd | null | 2014-01-01T00:08:00 | true | Cl.[NH2:2][C@@H:3]1[CH2:8][CH2:7][C@H:6]([NH:9][C:10]([C:12]2[C:16]3=[N:17][CH:18]=[CH:19][C:20]([C:21]4[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][C:22]=4[O:29][CH2:30][CH:31]4[CH2:33][CH2:32]4)=[C:15]3[NH:14][C:13]=2[CH3:34])=[O:11])[CH2:5][CH2:4]1.C([O:38][C@@H:39]([CH3:43])[C:40](Cl)=[O:41])(=O)C>>[CH:31]1([CH2:30][O:29][C:22]2[CH:23]=[C:24]([O:27][CH3:28])[CH:25]=[CH:26][C:21]=2[C:20]2[CH:19]=[CH:18][N:17]=[C:16]3[C:12]([C:10]([NH:9][C@H:6]4[CH2:7][CH2:8][C@@H:3]([NH:2][C:40](=[O:41])[C@@H:39]([OH:38])[CH3:43])[CH2:4][CH2:5]4)=[O:11])=[C:13]([CH3:34])[NH:14][C:15]=23)[CH2:32][CH2:33]1 | CC(=O)O[C@@H](C)C(=O)Cl | COc1ccc(-c2ccnc3c(C(=O)N[C@H]4CC[C@@H](N)CC4)c(C)[nH]c23)c(OCC2CC2)c1 | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Starting from N-(cis-4-aminocyclohexyl)-7-[2-(cyclopropylmethoxy)-4-methoxyphenyl]-2-methyl-1H-pyrrolo[3,2-b]pyridine-3-carboxamide hydrochloride (example D.f13) and commercially available (2S)-1-chloro-1-oxopropan-2-yl acetate the title compound is obtained as colorless solid. | COc1ccc(-c2ccnc3c(C(=O)N[C@H]4CC[C@@H](NC(=O)[C@H](C)O)CC4)c(C)[nH]c23)c(OCC2CC2)c1 | null | null | null |
275,975 | ord_dataset-02ee2261663048188cf6d85d2cc96e3f | null | 1993-01-01T00:09:00 | true | [CH3:1][C:2]([Si:5]([CH3:23])([CH3:22])[O:6][CH2:7][C@H:8]1[C@H:12]([CH2:13][O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])[C:9]21[O:11][CH2:10]2)([CH3:4])[CH3:3].[I-].[Li+]>C(Cl)Cl>[CH3:4][C:2]([Si:5]([CH3:22])([CH3:23])[O:6][CH2:7][C@H:8]1[C@H:12]([CH2:13][O:14][Si:15]([C:18]([CH3:20])([CH3:19])[CH3:21])([CH3:16])[CH3:17])[CH2:10][C:9]1=[O:11])([CH3:3])[CH3:1] | CC(C)(C)[Si](C)(C)OC[C@H]1[C@H](CO[Si](C)(C)C(C)(C)C)C12CO2 | null | null | [I-] | [Li+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | 0 | 1 | A solution of 12.752 g (35.6 mmol) of [4R,5R]-4,5-bis(((1,1-dimethylethyl)-dimethylsilyl)oxymethyl)-1-oxaspiro[2,2]pentane, from Step D, in 50 mL of methylene chloride was added to a solution of 3.814 g (28.5 mmol) of lithium iodide in 200 mL of methylene chloride which had been cooled in an ice bath. After stirring the reaction mixture for 1 h at 0° C., the ice bath was removed and the reaction mixture was stirred for 20 minutes at ambient temperature. The reaction mixture was then washed with 5% aqueous sodium bicarbonate solution, 5% sodium bisulfite solution and brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give 12.317 g (96.6% crude yield) of the title compound which was taken on to the next step without purifiaction; MS DCI-NH3M/Z: 376 (M+NH4)+. | CC(C)(C)[Si](C)(C)OC[C@@H]1CC(=O)[C@H]1CO[Si](C)(C)C(C)(C)C | null | null | null |
528,577 | ord_dataset-f027aa93238e424fbbf9bad1c7699adc | null | 2001-01-01T00:12:00 | true | [CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][CH2:14][C:15]([C:17]1[CH:22]=[CH:21][C:20]([Br:23])=[CH:19][CH:18]=1)=[O:16].[BH4-].[Na+]>C1COCC1.C(O)C>[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)=[N:4][C:3]=1[CH2:13][CH2:14][CH:15]([C:17]1[CH:22]=[CH:21][C:20]([Br:23])=[CH:19][CH:18]=1)[OH:16] | Cc1oc(-c2ccccc2)nc1CCC(=O)c1ccc(Br)cc1 | null | null | [BH4-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | CCO | null | null | null | null | null | null | null | null | null | 0 | 3 | The title compound of Example 2 (5.0 g, 13 mmol) was dissolved in THF (75 mL) and added dropwise over 20 minutes to a suspension of sodium borohydride (513 mg, 13 mmol) in 75 mL of ethanol at 0° C. and the reaction mixture was stirred for 3 hours at 0° C. The reaction mixture was poured onto ice-water (500 mL) and extracted twice with diethyl ether (700 mL). The organic extracts were combined and washed with water (250 mL), brine (250 mL) and dried (MgSO4). The solvent was removed in vacuo and the residue was recrystallized from hexane to afford 4.4 g (92%) of the racemic title compound. mp 82-83° C. 1HNMR (60 MHz, CDCl3): δ2.0 (m, 2H), 2.2 (s, 3H), 2.5 (t, J=6 Hz, 2H), 4.6 (m, 1H), 4.7 (broad s, 1H, hydroxyl proton), 7.1-7.5 (m, 7H), 7.8-8.0 (m, 2H). | Cc1oc(-c2ccccc2)nc1CCC(O)c1ccc(Br)cc1 | null | 90.9 | null |
1,101,975 | ord_dataset-af85e6f81c2d49f08086afd6d9e6959c | null | 2011-01-01T00:10:00 | true | [NH2:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][CH:21]=1)[O:5][C:6]1[CH:7]=[CH:8][C:9]2[N:10]([CH:12]=[C:13]([C:15]([NH:17][CH3:18])=[O:16])[N:14]=2)[N:11]=1.[CH3:22][N:23]1[C:27]([C:28](Cl)=[O:29])=[CH:26][C:25]([CH3:31])=[N:24]1.O>CN(C)C(=O)C>[CH3:22][N:23]1[C:27]([C:28]([NH:1][C:2]2[CH:3]=[C:4]([CH:19]=[CH:20][CH:21]=2)[O:5][C:6]2[CH:7]=[CH:8][C:9]3[N:10]([CH:12]=[C:13]([C:15]([NH:17][CH3:18])=[O:16])[N:14]=3)[N:11]=2)=[O:29])=[CH:26][C:25]([CH3:31])=[N:24]1 | CNC(=O)c1cn2nc(Oc3cccc(N)c3)ccc2n1 | Cc1cc(C(=O)Cl)n(C)n1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(=O)N(C)C | O | null | null | null | null | null | null | null | null | null | 25 | 1 | To a solution of 6-(3-aminophenoxy)-N-methylimidazo[1,2-b]pyridazine-2-carboxamide (250 mg, 0.88 mmol) in N,N-dimethylacetamide (2.5 mL) was added 1,3-dimethyl-1H-pyrazole-5-carbonyl chloride (253 mg, 1.59 mmol). After stirring at room temperature for 1 hr, water was added to the reaction mixture, and the precipitate was collected by filtration. The obtained residue was washed with water, acetonitrile and diethyl ether to give the title compound (262 mg, 73%) as a white powder. | CNC(=O)c1cn2nc(Oc3cccc(NC(=O)c4cc(C)nn4C)c3)ccc2n1 | null | 73.4 | null |
1,288,375 | ord_dataset-d5c54236ecd94d61aaa071461bcfc426 | null | 2013-01-01T00:04:00 | true | [OH-].[K+].[N:3]1[CH:8]=[CH:7][C:6]([CH:9]=[O:10])=[CH:5][CH:4]=1.[N+:11]([CH2:13][C:14]([N:16]1[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]1)=[O:15])#[C-:12]>CO>[N:3]1[CH:8]=[CH:7][C:6]([C@@H:9]2[O:10][CH:12]=[N:11][C@H:13]2[C:14]([N:16]2[CH2:17][CH2:18][N:19]([CH3:22])[CH2:20][CH2:21]2)=[O:15])=[CH:5][CH:4]=1 | O=Cc1ccncc1 | [C-]#[N+]CC(=O)N1CCN(C)CC1 | 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 | null | To a stirred and cooled (0° C.) solution of KOH (0.335 g, 5.98 mmol) in 7 mL MeOH were added successively pyridine-4-carbaldehyde (0.705 g, 6.58 mmol) and 2-isocyano-1-(4-methyl-piperazin-1-yl)-ethanone VIB 01128 (1.00 g, 6.58 mmol). The mixture was stirred at 0° C. until precipitation and concentrated. The mixture was partitioned between EtOAc (20 mL) and H2O (10 mL). The aqueous layer was extracted twice with EtOAc (60 mL). The EtOAc fractions were combined, washed twice with brine (2×10 mL), dried over MgSO4 and filtered. After evaporation and drying trans-(4,5-dihydro-5-(pyridin-4-yl)oxazol-4-yl)(4-methylpiperazin-1-yl)methanone VIB 01130 was obtained (1.282 g, 78% yield) as a yellow oil. | CN1CCN(C(=O)[C@@H]2N=CO[C@H]2c2ccncc2)CC1 | null | 78 | null |
537,584 | ord_dataset-1884c7bf3d544afdb8d17b5d41b90a27 | null | 2002-01-01T00:03:00 | true | [NH2:1][C:2]1[C:10]([N+:11]([O-])=O)=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[H][H]>CO.[Pd]>[NH2:1][C:2]1[C:10]([NH2:11])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5] | Nc1c(C(=O)O)cccc1[N+](=O)[O-] | [H][H] | null | [Pd] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | null | 4 | 14 g (76.9 mmol) of 2-amino-3-nitrobenzoic acid (1b) were dissolved in 500 ml of methanol, treated with Pd/C, and hydrogenated with hydrogen. After 4 h, the catalyst was filtered off with suction and concentrated. A dark-brown solid was obtained. Yield: 11.67 g (99%). | Nc1cccc(C(=O)O)c1N | null | null | null |
1,209,087 | ord_dataset-fb72428f30234761b4216139dc228d0c | null | 2012-01-01T00:09:00 | true | Br[C:2]1[CH:3]=[N:4][N:5]([CH3:18])[C:6]=1[C:7]1[CH:8]=[C:9]([C:14]([O:16][CH3:17])=[O:15])[S:10][C:11]=1[CH2:12][CH3:13].C(=O)([O-])[O-].[K+].[K+].O1CCO[CH2:27][CH2:26]1>O.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH:26]([C:2]1[CH:3]=[N:4][N:5]([CH3:18])[C:6]=1[C:7]1[CH:8]=[C:9]([C:14]([O:16][CH3:17])=[O:15])[S:10][C:11]=1[CH2:12][CH3:13])=[CH2:27] | CCc1sc(C(=O)OC)cc1-c1c(Br)cnn1C | C1COCCO1 | null | CC(C)(C)[P]([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)(C(C)(C)C)C(C)(C)C | O=C([O-])[O-] | [K+] | 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 | A solution of methyl 4-(4-bromo-1-methyl-1H-pyrazol-5-yl)-5-ethyl-2-thiophenecarboxylate (300 mg, 0.91 mmol), potassium carbonate (630 mg, 4.56 mmol), bis(tri-t-butylphosphine)palladium(0) (23 mg, 0.05 mmol) and 2,4,6-trivinylcycloboroxane-pyridine complex (110 mg, 0.46 mmol) in 1,4-dioxane (5 ml) and water (1 ml) was stirred at 80° C. in a sealed tube for 2 h. The reaction contents were partitioned between H2O-DCM and the aqueous phase was washed several times with DCM. The combined organic fractions were dried over Na2SO4, concentrated and purified via column chromatography (10-50% EtOAc in hexanes) affording methyl 4-(4-ethenyl-1-methyl-1H-pyrazol-5-yl)-5-ethyl-2-thiophenecarboxylate (187 mg, 0.66 mmol, 73% yield) as a clear oil: LCMS (ES) m/z=277 (M+H)+. | C=Cc1cnn(C)c1-c1cc(C(=O)OC)sc1CC | null | 73 | null |
1,302,638 | ord_dataset-78c3f723155a4347a902b53bcee1524d | null | 2013-01-01T00:06:00 | true | Cl[CH2:2][C:3]1[N:4]=[C:5]([NH:18][C:19](=[O:28])[C:20]2[C:25]([F:26])=[CH:24][CH:23]=[CH:22][C:21]=2[F:27])[S:6][C:7]=1[C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=1.[NH:29]([CH3:31])[CH3:30].CCN(CC)CC>C1COCC1>[CH3:30][N:29]([CH2:2][C:3]1[N:4]=[C:5]([NH:18][C:19](=[O:28])[C:20]2[C:25]([F:26])=[CH:24][CH:23]=[CH:22][C:21]=2[F:27])[S:6][C:7]=1[C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=1)[CH3:31] | CNC | O=C(Nc1nc(CCl)c(-c2cccc(C(F)(F)F)c2)s1)c1c(F)cccc1F | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(CC)CC | C1CCOC1 | null | null | null | null | null | null | null | null | null | 25 | 1 | Into a solution of Compound 70 (50 mg, 0.12 mmol) in 5 mL of THF was added NH(Me)2 (40% solution in water, 0.1 mL) and NEt3 (0.1 ml) at room temperature. The solution was stirred at room temperature for 1 hour. The solution was washed with 5 mL of water and dried (Na2SO4), filtered and concentrated. The residue was purified on silica (eluted with 5-100% ethyl acetate in hexane) to give Compound 71 (44 mg, 84%) as a white solid. | CN(C)Cc1nc(NC(=O)c2c(F)cccc2F)sc1-c1cccc(C(F)(F)F)c1 | null | 84 | null |
303,877 | ord_dataset-bfcf5a01f1a04ec585ba3f28cb93c8c9 | null | 1995-01-01T00:01:00 | true | Cl.[CH2:2]([CH:10]1[CH2:18][C:17]2[C:12](=[CH:13][CH:14]=[C:15]([C:19](=[NH:21])[NH2:20])[CH:16]=2)[CH2:11]1)[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9].C[O-].[Na+]>CO>[CH2:2]([CH:10]1[CH2:18][C:17]2[C:12](=[CH:13][CH:14]=[C:15]([C:19]3[N:20]=[CH:13][C:12]([CH2:11][CH2:10][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9])=[CH:17][N:21]=3)[CH:16]=2)[CH2:11]1)[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9] | CCCCCCCCC1Cc2ccc(C(=N)N)cc2C1 | null | null | C[O-] | Cl | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | null | 48 | 1.00 g (3.24 mM) of 2-octyl-5-amidinoindan hydrochloride, 0.40 g (7.40 mM) of sodium methylate, 0.82 g (3.43 mM) of α-octyloxy-β-dimethylaminoacrolein and 15 ml of methanol were placed in a 30 ml-round bottomed flask, followed by refluxing for 10.5 hours under stirring. After the reaction, the reaction mixture was left standing in a refrigerator for 2 days to precipitate a crystal. The crystal was recovered by filtration and dissolved in toluene, followed by drying with anhydrous sodium sulfate and filtration. The filtrate was evaporated to obtain a residue. The residue was purified by silica gel column chromatography (eluent: toluene/ethyl acetate=100/1) and recrystallized from a mixture solvent (toluene/methanol) to obtain 0.79 g of 2-octyl-5-(5-decylpyrimidine-2-yl)indan (Yield: 54.4%). ##STR151## | CCCCCCCCCCc1cnc(-c2ccc3c(c2)CC(CCCCCCCC)C3)nc1 | null | 108.8 | null |
137,638 | ord_dataset-3fa0a6b7d51b4fc6a5380aa0d03ac884 | null | 1985-01-01T00:12:00 | true | [NH:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[CH2:11][C:12]([OH:14])=O)[C:2]([NH2:4])=[O:3].FC(F)(F)C(OC(=O)C(F)(F)F)=O>FC(F)(F)C(O)=O>[N:1]1([C:2]([NH2:4])=[O:3])[C:5]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:11][C:12]1=[O:14] | NC(=O)Nc1ccccc1CC(=O)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 | O=C(OC(=O)C(F)(F)F)C(F)(F)F | null | null | null | null | null | null | null | null | null | null | null | To a solution of 194 mg (1.0 mmole) of 2-(2-ureidophenyl)acetic acid in 4 ml of trifluoroacetic acid was added 630 mg (3.0 mmole) of trifluoroacetic anhydride, and the mixture was then heated under reflux for ca. 1 hour. The reaction mixture was cooled and the solvent was removed by evaporation in vacuo. The residue was triturated under 5-8 ml of saturated sodium bicarbonate solution, and the material which remained out of solution was collected by filtration. The solid thus obtained was recrystallized from ethanol to give 61 mg of the title compound as colorless needles, m.p. 179°-180° C. (slight decomposition). | NC(=O)N1C(=O)Cc2ccccc21 | null | 34.6 | null |
1,400,742 | ord_dataset-12dc3bd21bcf44d09e5b4249afe15161 | null | 2014-01-01T00:02:00 | true | [C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:17]3[C:25]4[C:20](=[CH:21][C:22]([F:26])=[CH:23][CH:24]=4)[N:19]([CH2:27][CH:28]4[CH2:31][N:30](C(OC(C)(C)C)=O)[CH2:29]4)[N:18]=3)[N:15]=2)[N:10](COCC[Si](C)(C)C)[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:47][C:48]([F:53])([F:52])[C:49]([OH:51])=[O:50]>ClCCl>[F:47][C:48]([F:53])([F:52])[C:49]([OH:51])=[O:50].[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:17]3[C:25]4[C:20](=[CH:21][C:22]([F:26])=[CH:23][CH:24]=4)[N:19]([CH2:27][CH:28]4[CH2:29][NH:30][CH2:31]4)[N:18]=3)[N:15]=2)[NH:10][CH:9]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3] | CC(C)(C)NC(=O)c1cn(COCC[Si](C)(C)C)c2ncc(-c3nn(CC4CN(C(=O)OC(C)(C)C)C4)c4cc(F)ccc34)nc12 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O=C(O)C(F)(F)F | ClCCl | null | null | null | null | null | null | null | null | null | null | null | To a stirred solution of tert-butyl 3-((3-(7-(tert-butylcarbamoyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)-6-fluoro-1H-indazol-1-yl)methyl)azetidine-1-carboxylate (70 mg, 107 μmol) in dichloromethane (5 mL) was added trifluoroacetic acid (1 mL). After 15 h the mixture was concentrated in vacuo and the residue dissolved in 25 mL of a Jan. 10, 1960 mixture of ammonium hydroxide/methanol/dichloromethane. After 1 h the mixture was concentrated in vacuo. Purification by chromatography (silica, 24 g Analogix column, 0-6% methanol containing 10% ammonium hydroxide in dichloromethane) followed by SFC chromatography (eluent contained TFA) gave 2-(1-azetidin-3-ylmethyl-6-fluoro-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butyl amide trifluoroacetate (10 mg, 17%). MS (M+H)+=422; 1H NMR (DMSO-d6) δ: 9.09 (s, 1H), 8.49 (dd, J=8.9, 5.4 Hz, 1H), 8.40 (s, 1H), 7.92 (s, 1H), 7.77 (dd, J=9.8, 1.9 Hz, 1H), 7.20 (d, J=2.1 Hz, 1H), 4.77 (d, J=7.0 Hz, 2H), 3.87-4.18 (m, 4H), 1.52 (s, 9H), 1.24 (d, J=4.5 Hz, 1H). | CC(C)(C)NC(=O)c1c[nH]c2ncc(-c3nn(CC4CNC4)c4cc(F)ccc34)nc12 | null | 17 | null |
738,143 | ord_dataset-76dd1b78ee414d2da0ed30700ef026f7 | null | 2006-01-01T00:10:00 | true | [O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH:10]([O:14][CH3:15])[C:11]([OH:13])=O)=[CH:9][C:4]=2[O:3][CH2:2]1.[NH2:16][CH2:17][C:18]1[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[CH:20][CH:19]=1>>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH:10]([O:14][CH3:15])[C:11]([NH:23][CH2:22][C:21]3[CH:24]=[CH:25][C:18]([C:17]#[N:16])=[CH:19][CH:20]=3)=[O:13])=[CH:9][C:4]=2[O:3][CH2:2]1 | COC(C(=O)O)c1ccc2c(c1)OCO2 | N#Cc1ccc(CN)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 | (RS)-Benzo[1,3]dioxol-5-yl-methoxy-acetic acid was coupled with 4-aminomethyl benzonitrile according to general procedure C to give (RS)-2-benzo[1,3]dioxol-5-yl-N-(4-cyano-benzyl)-2-methoxy-acetamide. Light yellow solid. | COC(C(=O)NCc1ccc(C#N)cc1)c1ccc2c(c1)OCO2 | null | null | null |
362,906 | ord_dataset-0b24d1f58a024ed7bc2bda95b2430c72 | null | 1997-01-01T00:04:00 | true | [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][N:7]=[C:6]2[N:15]1[CH2:20][CH2:19][CH:18]([N:21]2[C:30](=[O:31])[C:29]3[C:24](=[CH:25][CH:26]=[C:27]([N+:32]([O-:34])=[O:33])[CH:28]=3)[NH:23][C:22]2=[O:35])[CH2:17][CH2:16]1.[CH:36]1([CH2:39]Br)[CH2:38][CH2:37]1>>[CH:36]1([CH2:39][N:23]2[C:24]3[C:29](=[CH:28][C:27]([N+:32]([O-:34])=[O:33])=[CH:26][CH:25]=3)[C:30](=[O:31])[N:21]([CH:18]3[CH2:19][CH2:20][N:15]([C:6]4[C:5]5[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=5)[N:9]=[CH:8][N:7]=4)[CH2:16][CH2:17]3)[C:22]2=[O:35])[CH2:38][CH2:37]1 | COc1cc2ncnc(N3CCC(n4c(=O)[nH]c5ccc([N+](=O)[O-])cc5c4=O)CC3)c2cc1OC | BrCC1CC1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The procedure similar to that described in Example 1 was repeated, except that 300 mg (0.63 mmol) of Compound 24 was used and cyclopropylmethyl bromide was used in place of methyl iodide. As a result, 89 mg (yield: 27%) of Compound 26 was obtained as pale yellow crystals. | COc1cc2ncnc(N3CCC(n4c(=O)c5cc([N+](=O)[O-])ccc5n(CC5CC5)c4=O)CC3)c2cc1OC | null | 27 | null |
1,346,975 | ord_dataset-6034127657614f02860ed057b62b882e | null | 2013-01-01T00:10:00 | true | CC(N=NC(C#N)(C)C)([C:4]#[N:5])C.C1C(=O)N(Br)C(=O)C1.[CH3:21][C:22]1[CH:31]=[C:30]([N+:32]([O-:34])=[O:33])[CH:29]=[CH:28][C:23]=1[C:24](OC)=[O:25]>C(Cl)(Cl)(Cl)Cl>[CH3:4][N:5]1[CH2:21][C:22]2[C:23](=[CH:28][CH:29]=[C:30]([N+:32]([O-:34])=[O:33])[CH:31]=2)[C:24]1=[O:25] | CC(C)(C#N)N=NC(C)(C)C#N | COC(=O)c1ccc([N+](=O)[O-])cc1C | null | O=C1CCC(=O)N1Br | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClC(Cl)(Cl)Cl | null | null | null | null | null | null | null | null | null | null | 79 | 2 | AIBN (84 mg, 0.51), NBS (1.1 gram, 6.4 mmol), and the methyl 2-methyl-4-nitrobenzoate (1 g, 5.1 mmol, as prepared in Step 1, Example 44) were suspended in CCl4 (12.8 ml), the vessel evacuated and backfilled with N2 (2×) and the mixture heated under N2 at 79° C. overnight. The solution was filtered, and concentrated in vacuum. One third of the crude material was dissolved in 2 N methylamine in methanol (18 ml), 2N methylamine in THF added (18 ml) and the solution stirred for 2 hours at RT. The volatiles were removed in vacuum and the product was purified by chromatography on SiO2 eluting with 10% acetone:DCM to give the titled compound. | CN1Cc2cc([N+](=O)[O-])ccc2C1=O | null | null | null |
1,158,611 | ord_dataset-b195433d5c354ddfb6cde0d53c41910f | null | 2012-01-01T00:04:00 | true | [NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]([CH2:17][C:18]([O:20]C)=O)[CH2:5][N:6]2[CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[O:20]=[C:18]1[CH2:17][CH:4]2[CH2:5][N:6]([CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:7]3[C:3]2=[C:2]([CH:10]=[CH:9][CH:8]=3)[NH:1]1 | CCOC(=O)CN1CC(CC(=O)OC)c2c(N)cccc21 | null | null | Cc1ccc(S(=O)(=O)O)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Cc1ccccc1 | O | null | null | null | null | null | null | null | null | null | 25 | null | To a solution of (±)-ethyl methyl 2,2′-(4-amino-2,3-dihydro-1H-indole-1,3-diyl)diacetate from Step D (490 mg, 1.70 mmol) in toluene (35 mL) was added p-toluenesulfonic acid monohydrate (5 mg, 0.026 mmol) and the mixture was heated at reflux for 48 h. The mixture was cooled to ambient temperature and was partitioned between saturated aqueous NaHCO3 (5 mL) and EtOAc (40 mL). The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of CHCl3:EtOAc—90:10 to 40:60, to give the racemic product. The enantiomers were resolved by HPLC, utilizing a Chiralpak AS column and eluting with MeOH. The first major peak to elute was ethyl (4-oxo-2a,3,4,5-tetrahydropyrrolo[4,3,2-de]quinolin-1(2H)-yl)acetate, enantiomer A, and the second major peak to elute was ethyl (4-oxo-2a,3,4,5-tetrahydropyrrolo[4,3,2-de]quinolin-1(2H)-yl)acetate, enantiomer B, the title compound. MS: m/z=261 (M+1). | CCOC(=O)CN1CC2CC(=O)Nc3cccc1c32 | null | null | null |
1,544,440 | ord_dataset-cac8df8aff894288876df4e093c9877f | null | 2015-01-01T00:02:00 | true | [NH2:1][C:2]1[C:7]([N+:8]([O-])=O)=[CH:6][C:5]([OH:11])=[CH:4][C:3]=1[CH3:12]>CO.[Pd]>[NH2:8][C:7]1[CH:6]=[C:5]([OH:11])[CH:4]=[C:3]([CH3:12])[C:2]=1[NH2:1] | Cc1cc(O)cc([N+](=O)[O-])c1N | null | null | [Pd] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | null | null | 6.00 g (35.7 mmol) 4-amino-3-methyl-5-nitro-phenol in 200 mL MeOH was combined with 0.600 g palladium on charcoal (Pd/C 10%) and hydrogenated for 4 h under a hydrogen atmosphere of 60 psi at 50° C. The catalyst was removed by suction filtering, the filtrate was evaporated down and the residue was dried under HV. | Cc1cc(O)cc(N)c1N | null | null | null |
1,077,523 | ord_dataset-afd812677c134591a99f46ce28de2524 | null | 2011-01-01T00:08:00 | true | [Br:1][C:2]1[CH:3]=[C:4]([CH:23]2[C:32]3[C:31](=[O:33])[CH2:30][CH:29]([CH2:34][CH2:35][CH3:36])[CH2:28][C:27]=3[NH:26][C:25]([CH3:37])=[C:24]2[C:38]#[N:39])[CH:5]=[C:6]([O:20][CH2:21][CH3:22])[C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:11]=1[N+:17]([O-])=O.C(O)(=O)C>C1COCC1.[Zn]>[NH2:17][C:11]1[CH:12]=[CH:13][C:14]([F:16])=[CH:15][C:10]=1[CH2:9][O:8][C:7]1[C:6]([O:20][CH2:21][CH3:22])=[CH:5][C:4]([CH:23]2[C:32]3[C:31](=[O:33])[CH2:30][CH:29]([CH2:34][CH2:35][CH3:36])[CH2:28][C:27]=3[NH:26][C:25]([CH3:37])=[C:24]2[C:38]#[N:39])=[CH:3][C:2]=1[Br:1] | CCCC1CC(=O)C2=C(C1)NC(C)=C(C#N)C2c1cc(Br)c(OCc2cc(F)ccc2[N+](=O)[O-])c(OCC)c1 | null | null | [Zn] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(=O)O | C1CCOC1 | null | null | null | null | null | null | null | null | null | 50 | null | To a solution of the product of step b (3.8 g) in THF (110 ml) were added acetic acid (3.6 ml) and zinc dust (8.2 g). The suspension was heated for 1 h at 50° C. The reaction mixture was filtered and concentrated. The residue was dissolved in ethyl acetate and washed with sat. NalCO3 and brine. The organic layer was separated, dried (Na2SO4) and concentrated. The remaining solid was stirred with a small amount of ethyl acetate to give the title compound as a pale yellow solid after filtration. | CCCC1CC(=O)C2=C(C1)NC(C)=C(C#N)C2c1cc(Br)c(OCc2cc(F)ccc2N)c(OCC)c1 | null | null | null |
1,676,474 | ord_dataset-9cc455db05a444779921f786a45b21a6 | null | 2015-01-01T00:12:00 | true | [CH:1]1([C:6]2[N:7]=[C:8](O)[C:9]3[S:15](=[O:17])(=[O:16])[CH2:14][CH2:13][CH2:12][C:10]=3[N:11]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.P(Cl)(Cl)[Cl:20]>ClC(Cl)C>[Cl:20][C:8]1[C:9]2[S:15](=[O:17])(=[O:16])[CH2:14][CH2:13][CH2:12][C:10]=2[N:11]=[C:6]([CH:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)[N:7]=1 | O=S1(=O)CCCc2nc(C3CCCC3)nc(O)c21 | ClP(Cl)Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(Cl)Cl | null | null | null | null | null | null | null | null | null | null | 65 | 24 | To mixture of 2-cyclopentyl-4-hydroxy-7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidine 5,5-dioxide (0.650 g, 2.42 mmol) in dichloroethane (10 mL) was added phosphorous trichloride (1.35 mL, 14.5 mmol). The mixture was stirred at 65° C. for 24 h. The reaction was quenched into a mixture of methylene chloride and a saturated solution of NaHCO3 and extracted with methylene chloride. The organic layers were dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The residue was purified by column chromatography (silica, hexanes/ethyl acetate) to afford the title compound (0.150 g, 22%) as a tan solid. MW=286.78. 1H NMR (CDCl3, 500 MHz) δ 3.49-3.42 (m, 2H), 3.31 (p, J=8.0 Hz, 1H), 3.11 (t, J=6.2 Hz, 2H), 2.53-2.45 (m, 2H), 2.13-2.04 (m, 2H), 1.94-1.78 (m, 4H), 1.75-1.65 (m, 2H); APCI MS m/z 287 [M+H]+. | O=S1(=O)CCCc2nc(C3CCCC3)nc(Cl)c21 | null | 21.6 | null |
989,656 | ord_dataset-b6d8835b0c934476a36e6149e7597487 | null | 2010-01-01T00:09:00 | true | CI.[C:3](=O)([O-])[O-].[K+].[K+].[NH2:9][C:10]1[C:15]([OH:16])=[CH:14][CH:13]=[CH:12][C:11]=1[C:17](=[O:19])[CH3:18]>CN(C=O)C>[NH2:9][C:10]1[C:15]([O:16][CH3:3])=[CH:14][CH:13]=[CH:12][C:11]=1[C:17](=[O:19])[CH3:18] | O=C([O-])[O-] | CC(=O)c1cccc(O)c1N | null | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CI | CN(C)C=O | null | null | null | null | null | null | null | null | null | 25 | 1 | Under an atmosphere of nitrogen, methyl iodide (1.35 g, 10 mmol) and potassium carbonate (4.39 g, 320 mmol) were added to a solution of 2′-amino-3′-hydroxyacetophenone (960 mg, 6 mmol, TCI Europe) in DMF (6 ml). The reaction mixture was stirred for 1 h at r.t., during which time the color of the mixture changed from light brown to dark green. The mixture was then worked up by extraction with H2O/ethyl acetate, drying of the organic phase (Na2SO4), and evaporation of solvent. The title compound (960 mg, 92%) was isolated from the residue by column chromatography (silica gel, heptan/ethyl acetate=100/0-70/30). | COc1cccc(C(C)=O)c1N | null | 96.9 | null |
1,560,074 | ord_dataset-4e54080057a44c3887653391e24c90b6 | null | 2015-01-01T00:03:00 | true | CN([CH:4]=[C:5]1[C:10](=O)[C:9]([O:12][CH2:13][CH3:14])=[CH:8][CH2:7][CH2:6]1)C.[CH2:15]([S:22][C:23](=[NH:25])[NH2:24])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>CN(C)C=O>[CH2:15]([S:22][C:23]1[N:24]=[CH:4][C:5]2[CH2:6][CH2:7][CH:8]=[C:9]([O:12][CH2:13][CH3:14])[C:10]=2[N:25]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1 | N=C(N)SCc1ccccc1 | CCOC1=CCCC(=CN(C)C)C1=O | null | null | 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 | 95 | 4 | To a solution of 2.0 g (0.01 mol) of 6-[(dimethylamino)methylene]-2-ethoxycyclohex-2-en-1-one in 20 mL of dimethylformamide 2.6 g of S-benzylisothiourea (2 eq. mol.) were added. The reaction mixture was stirred at 95° C. for 4 hours. The solvent was then evaporated under reduced pressure and the crude purified by chromatography on a silica gel column (eluant dichloromethane/methanol 9/1) leading 1.5 g (50% yield) of the title compound. | CCOC1=CCCc2cnc(SCc3ccccc3)nc21 | null | 50 | null |
1,129,320 | ord_dataset-285df12e34cd46e993e3c8ebc3a8962a | null | 2012-01-01T00:01:00 | true | [CH3:1][CH:2]([CH3:16])[CH2:3][NH:4][C:5]([C:7]1[CH:12]=[CH:11][C:10](B(O)O)=[CH:9][CH:8]=1)=[O:6].Br[C:18]1[CH:23]=[CH:22][C:21]([O:24][CH2:25][CH:26]2[CH2:31][CH2:30][N:29]([C:32]([O:34][CH:35]([CH3:37])[CH3:36])=[O:33])[CH2:28][CH2:27]2)=[CH:20][CH:19]=1>>[CH3:1][CH:2]([CH3:16])[CH2:3][NH:4][C:5]([C:7]1[CH:12]=[CH:11][C:10]([C:18]2[CH:19]=[CH:20][C:21]([O:24][CH2:25][CH:26]3[CH2:27][CH2:28][N:29]([C:32]([O:34][CH:35]([CH3:37])[CH3:36])=[O:33])[CH2:30][CH2:31]3)=[CH:22][CH:23]=2)=[CH:9][CH:8]=1)=[O:6] | CC(C)CNC(=O)c1ccc(B(O)O)cc1 | CC(C)OC(=O)N1CCC(COc2ccc(Br)cc2)CC1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The title compound (21 mg, 19%) was prepared from (4-{[(2-methylpropyl)amino]carbonyl}phenyl)boronic acid (44 mg, 0.2 mmol) and 1-methylethyl 4-{[(4-bromophenyl)oxy]methyl}-1-piperidinecarboxylate (prepared as in Example 9, Step 2, 71 mg, 0.2 mmol) in a manner similar to Example 21, Step 3 and worked up in a manner similar to Example 9, Step 3. 1H NMR (400 MHz, CDCl3): δ 7.80 (d, 2H, J=8.6 Hz), 7.60 (d, 2H, J=8.6 Hz), 7.54 (d, 2H, J=8.8 Hz), 6.96 (d, 2H, J=8.9 Hz), 6.17 (t, 1H, J=5.8 Hz), 4.97-4.84 (m, 1H), 4.21 (bs, 2H), 3.85 (d, 2H, J=6.4 Hz), 3.34-3.27 (m, 2H), 2.83-2.73 (m, 2H), 2.05-1.95 (m, 1H), 1.95-1.89 (m, 1H), 1.90-1.80 (m, 2H), 1.35-1.26 (m, 2H), 1.24 (d, 6H, J=6.2 Hz), 0.99 (d, 6H, J=6.7 Hz); LRMS (ESI), m/z 453 (M+H). | CC(C)CNC(=O)c1ccc(-c2ccc(OCC3CCN(C(=O)OC(C)C)CC3)cc2)cc1 | null | 23.2 | null |
1,009,194 | ord_dataset-7448b89163bf426c9d9777809ce24cec | null | 2010-01-01T00:11:00 | true | [O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH2:12][C:13]1[CH:14]=[C:15]2[C:20](=[CH:21][CH:22]=1)[N:19]=[C:18]([CH:23]=[CH:24][C:25]#[N:26])[CH:17]=[CH:16]2>C(O)C.C(Cl)(Cl)Cl.[OH-].[Pd+2].[OH-].[C]>[O:11]=[C:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:2](=[O:1])[N:3]1[CH2:12][C:13]1[CH:14]=[C:15]2[C:20](=[CH:21][CH:22]=1)[N:19]=[C:18]([CH2:23][CH2:24][C:25]#[N:26])[CH:17]=[CH:16]2 | N#CC=Cc1ccc2cc(CN3C(=O)c4ccccc4C3=O)ccc2n1 | null | null | [Pd+2] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClC(Cl)Cl | CCO | null | null | null | null | null | null | null | null | null | 25 | 16 | The compound (574.4 mg) obtained in Example 119-6 was dissolved in ethanol (20 ml) and chloroform (10 ml). Then, the solution was added with 20% palladium hydroxide-carbon (172.3 mg) and then stirred at room temperature for 16 hours under a hydrogen atmosphere. After the reaction, the solution was filtrated through Celite and the solvent was then distilled off under reduced pressure. The residue was purified through silica gel column chromatography (hexane/ethyl acetate), thereby obtaining the subject compound (101.9 mg) as a yellow solid. | N#CCCc1ccc2cc(CN3C(=O)c4ccccc4C3=O)ccc2n1 | null | 17.6 | null |
1,341,276 | ord_dataset-08852243bba44cb28769a5833f1515fe | null | 2013-01-01T00:09:00 | true | Cl[C:2]1[N:7]=[CH:6][C:5]([S:8]([N:11]([CH2:18][CH:19]2[CH2:23][O:22][C:21]([CH3:25])([CH3:24])[O:20]2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.O.[NH2:27][NH2:28]>>[CH3:24][C:21]1([CH3:25])[O:20][CH:19]([CH2:18][N:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[S:8]([C:5]2[CH:6]=[N:7][C:2]([NH:27][NH2:28])=[CH:3][CH:4]=2)(=[O:10])=[O:9])[CH2:23][O:22]1 | CC1(C)OCC(CN(c2ccccc2)S(=O)(=O)c2ccc(Cl)nc2)O1 | NN | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | null | null | null | null | null | null | null | null | null | null | null | null | According to process 5.2, starting with 0.54 g of 6-chloro-N-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]-N-phenylpyridine-3-sulfonamide and 30 μL of hydrazine hydrate, 0.53 g of N-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]-6-hydrazinyl-N-phenylpyridine-3-sulfonamide is obtained in the form of a white solid. | CC1(C)OCC(CN(c2ccccc2)S(=O)(=O)c2ccc(NN)nc2)O1 | null | 99 | null |
1,569,507 | ord_dataset-9741bb5fd93044078df2a45f45733054 | null | 2015-01-01T00:04:00 | true | [CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH2:9]/[CH:10]=[C:11](\[CH3:23])/[CH2:12][CH2:13]/[CH:14]=[C:15](\[CH3:22])/[CH2:16][CH2:17][CH:18]=[C:19]([CH3:21])[CH3:20])[CH:6]=[C:5]([CH3:24])[CH:4]=1.C1C=C(Cl)C=C(C(OO)=[O:33])C=1>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH2:9]/[CH:10]=[C:11](\[CH3:23])/[CH2:12][CH2:13]/[CH:14]=[C:15](\[CH3:22])/[CH2:16][CH2:17][CH:18]2[O:33][C:19]2([CH3:20])[CH3:21])[CH:6]=[C:5]([CH3:24])[CH:4]=1 | O=C(OO)c1cccc(Cl)c1 | COc1cc(C)cc(C/C=C(\C)CC/C=C(\C)CCC=C(C)C)c1 | 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 | 0 | 1 | To a solution of 24 (488.2 mg, 1.5 mmol) in 12 mL of dry CH2Cl2 at 0° C. was added a solution of MCPBA (403.4 mg, 1.80 mmol in 4 mL of CH2Cl2), the reaction mixture was stirred at 0° C. for 1 hr and then quenched with saturated aqueous NaHCO3 (50 mL). Et2O (3×50 mL) was then added, and the organic layer was washed with saturated aqueous NaHCO3, water, and brine, and dried with MgSO4 and concentrated to give a crude product. The crude product was passed through a silica gel column (hexanes/EtOAc 80:1, 40:1, 20:1) to give the pure epoxide 25 (104 mg: yield 20%) as a colorless oil. | COc1cc(C)cc(C/C=C(\C)CC/C=C(\C)CCC2OC2(C)C)c1 | null | 20.2 | null |
557,788 | ord_dataset-f483e698250b4da0a84f425c7bfa965a | null | 2002-01-01T00:08:00 | true | [H-].[Na+].[C:3]([O:7][C:8]([NH:10][C:11]1[CH:31]=[CH:30][C:14]([O:15][C:16]2[CH:17]=[CH:18][C:19]([N+:27]([O-:29])=[O:28])=[C:20]([N:22]([CH3:26])[C:23](=[O:25])[O-:24])[CH:21]=2)=[CH:13][CH:12]=1)=[O:9])([CH3:6])([CH3:5])[CH3:4].[CH2:32](Br)[CH2:33][CH2:34][CH2:35][CH2:36][CH3:37]>CN(C)C=O>[C:3]([O:7][C:8]([N:10]([CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])[C:11]1[CH:31]=[CH:30][C:14]([O:15][C:16]2[CH:17]=[CH:18][C:19]([N+:27]([O-:29])=[O:28])=[C:20]([N:22]([CH3:26])[C:23](=[O:24])[O:25][C:3]([CH3:6])([CH3:5])[CH3:4])[CH:21]=2)=[CH:13][CH:12]=1)=[O:9])([CH3:6])([CH3:4])[CH3:5] | CCCCCCBr | CN(C(=O)[O-])c1cc(Oc2ccc(NC(=O)OC(C)(C)C)cc2)ccc1[N+](=O)[O-] | null | [H-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | 25 | 1 | To a suspension of sodium hydride (55 wt. %, 1.26 g) in anhydrous N,N-dimethylformamide (100 ml) was added N-[5-(4-t-butoxycarbonylaminophenoxy)-2-nitrophenyl]-N-methylcarbamate (12.1 g). The mixture was stirred at ambient temperature for several minutes. To the mixture was added hexyl bromide (6.5 g) under ice cooling and the mixture was stirred at the same temperature for 30 minutes and then at room temperature for 1.0 hour. The reaction mixture was concentrated and the residue was partitioned between ethyl acetate and water. The ethyl acetate layer was dried over anhydrous sodium sulfate and concentrated. The residue was purified by chromatography on a silica gel column using toluene/diisopropyl ether=100/7 as the eluant to give the title compound (13.8 g). | CCCCCCN(C(=O)OC(C)(C)C)c1ccc(Oc2ccc([N+](=O)[O-])c(N(C)C(=O)OC(C)(C)C)c2)cc1 | null | 168.8 | null |
144,219 | ord_dataset-1895fe091c3f47afa1ee96a41a250de4 | null | 1986-01-01T00:05:00 | true | [CH2:1]([O:3][C:4]([C@@H:6]([NH:26][C@@H:27]1[C:33](=[O:34])[N:32]([CH2:35][C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[C:31]2[CH:43]=[CH:44][CH:45]=[CH:46][C:30]=2[O:29][CH2:28]1)[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][N:15]1[C:19](=[O:20])C2=CC=CC=C2C1=O)=[O:5])[CH3:2].[OH2:47].NN>C(O)C>[C:39]([O:20][C:19]([NH:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][C@H:6]([NH:26][C@@H:27]1[C:33](=[O:34])[N:32]([CH2:35][C:36]([O:38][C:39]([CH3:41])([CH3:42])[CH3:40])=[O:37])[C:31]2[CH:43]=[CH:44][CH:45]=[CH:46][C:30]=2[O:29][CH2:28]1)[C:4]([O:3][CH2:1][CH3:2])=[O:5])=[O:47])([CH3:42])([CH3:41])[CH3:40] | CCOC(=O)[C@H](CCCCCCCCN1C(=O)c2ccccc2C1=O)N[C@H]1COc2ccccc2N(CC(=O)OC(C)(C)C)C1=O | O | null | NN | 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 | A mixture of tert-butyl 3(S)-[1(S)-ethoxycarbonyl-9-phthalimidononyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate (0.46 g), hydrazine hydrate (0.18 g) and ethanol (10 ml) is allowed to stand overnight at room temperature. The mixture is concentrated under reduced pressure, diluted with water (50 ml) and extracted with ethyl acetate (50 ml×4). Water (50 ml) and sodium bicarbonate (0.5 g) are added to the organic extract, and to the resulting mixture is added dropwise di-tert-butyl dicarbonate (0.24 g) with stirring. After stirring for 30 minutes at room temperature, the ethyl acetate layer is dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue is purified by silica gel column chromatography using hexane-ethyl acetate (2:1) as an eluent to yield tert-butyl 3(S)-[9-tert-butoxycarbonylamino-1(S)-ethoxycarbonylnonyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate (0.35 g) as a colorless oil. | CCOC(=O)[C@H](CCCCCCCCNC(=O)OC(C)(C)C)N[C@H]1COc2ccccc2N(CC(=O)OC(C)(C)C)C1=O | null | 159.7 | null |
1,121,130 | ord_dataset-285df12e34cd46e993e3c8ebc3a8962a | null | 2012-01-01T00:01:00 | true | O[C:2]1[C:11]([NH:12][C:13](=[O:26])[C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20]3[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=3)[CH:15]=2)=[CH:10][CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].O.CC1C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[N:22]1[CH:23]=[CH:24][CH:25]=[C:20]([C:16]2[CH:15]=[C:14]([C:13]3[O:26][C:2]4[C:3]([C:4]([O:6][CH3:7])=[O:5])=[CH:8][CH:9]=[CH:10][C:11]=4[N:12]=3)[CH:19]=[CH:18][CH:17]=2)[CH:21]=1 | COC(=O)c1cccc(NC(=O)c2cccc(-c3cccnc3)c2)c1O | null | null | Cc1ccc(S(=O)(=O)O)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Cc1ccccc1 | O | null | null | null | null | null | null | null | null | null | null | null | Methyl 2-hydroxy-3-(3-(pyridin-3-yl)benzamido)benzoate (0.9 g, 2.5 mmol) and 4-methylbenzenesulfonic acid monohydrate (1 g, 5 mmol) were added to toluene (20 mL) and the mixture was stirred under reflux for 2 days. The resulting mixture was extracted with ethyl acetate (100 mL×4) and concentrated. The crude product was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=20:1 to 10:1). 130 mg of methyl 2-(3-(pyridin-3-yl)phenyl)benzo[d]oxazole-7-carboxylate as a solid was obtained. Yield: 15%. LC-MS (ESI) m/z: 331 (M+1)+. | COC(=O)c1cccc2nc(-c3cccc(-c4cccnc4)c3)oc12 | null | 15.7 | null |
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