Cesium carbonate → 1-[(2-Ethylphenyl)carbamothioyl]-3-[[4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]methyl]urea

HRID 924252노트

반응식

HRID 924252 반응식
[F:1][C:2]([F:24])([F:23])[O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH:14]=[N:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([CH2:21][NH2:22])=[CH:17][CH:16]=3)=[N:11]2)=[CH:6][CH:5]=1.[C:25](=[O:36])(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl.C([O-])(=O)C.[Na+].[CH2:42]([C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][C:45]=1[NH:50][C:51]([NH2:53])=[S:52])[CH3:43].C(=O)([O-])[O-].[Cs+].[Cs+]>ClCCl.O.C(#N)C>[CH2:42]([C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][C:45]=1[NH:50][C:51]([NH:53][C:25]([NH:22][CH2:21][C:18]1[CH:19]=[CH:20][C:15]([C:12]2[N:13]=[CH:14][N:10]([C:7]3[CH:6]=[CH:5][C:4]([O:3][C:2]([F:1])([F:23])[F:24])=[CH:9][CH:8]=3)[N:11]=2)=[CH:16][CH:17]=1)=[O:36])=[S:52])[CH3:43]

참가 물질

9

반응물 5

HCID 10796Cesium carbonateHCID 94429TriphosgeneHCID 517045Sodium AcetateHCID 2758895(2-Ethylphenyl)thioureaHCID 904040894-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenylmethanamine

생성물 1

HCID 904042641-[(2-Ethylphenyl)carbamothioyl]-3-[[4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]methyl]urea수율 51.5%

시약·촉매·용매 3

HCID 962Water용매2회HCID 6342Acetonitrile용매HCID 6344Dichloromethane용매3회

실험 절차

A fine suspension of (4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)methanamine (C16) (0.300 g, 0.897 mmol) in dichloromethane (4.0 mL) was added, in a slow dropwise fashion, to a biphasic solution of bis(trichloromethyl) carbonate (0.107 g, 0.359 mmol) and sodium acetate (0.221 g, 2.69 mmol) in dichloromethane (4.0 mL) and water (2.0 mL). The reaction was allowed to stir for 30 minutes. The reaction was passed through a phase separator, washing with additional dichloromethane and the organic layer was concentrated. The resulting residue was diluted with acetonitrile (4.0 mL), and 1-(2-ethylphenyl)thiourea (0.178 g, 0.987 mmol) and cesium carbonate (0.351 g, 1.08 mmol) were added as solids. The reaction was allowed to stir at room temperature overnight. The reaction mixture was diluted with dichloromethane and water and passed through a phase separator. The organic layer was concentrated on to Celite® and purified by reverse phase flash column chromatography (C18) using 20-100% acetonitrile/water as eluent providing the title compound as a white solid (0.100 g, 16%) contaminated with ˜20% of the dimer urea: 1H NMR (400 MHz, DMSO-d6) δ 11.99 (s, 1H), 10.24 (s, 1H), 9.41 (s, 1H), 9.40 (d, J=1.0 Hz, 1H), 8.18-8.03 (m, 6H), 7.63 (dddd, J=9.2, 4.3, 2.0, 1.0 Hz, 3H), 7.54 (ddd, J=12.1, 7.0, 4.8 Hz, 2H), 7.50-7.38 (m, 3H), 7.35-7.26 (m, 1H), 7.26-7.20 (m, 2H), 4.44 (d, J=5.8 Hz, 2H), 2.56 (q, J=7.6 Hz, 2H), 1.14 (t, J=7.6 Hz, 3H); 19F NMR (376 MHz, DMSO-d6) δ −56.96; ESIMS m/z 541 ([M+H]+), 539 ([M−H]−)

후처리

  1. washwashing with additional dichloromethane
  2. concentrationthe organic layer was concentrated
  3. additionwere added as solids
  4. stirringto stir at room temperature overnight
  5. concentrationThe organic layer was concentrated on to Celite®
  6. custompurified by reverse phase flash column chromatography (C18)

출처 및 근거

ORD 기록
ord-91b67d48394e45959a4de2432794259f
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09278964B2

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