tert-Butanol → tert-butyl 3-chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-5-fluorophenylcarbamate

HRID 1627267노트

반응식

HRID 1627267 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([F:37])[C:10]=1[CH2:11][S:12][C:13]1[N:14]([C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=2)[C:15]([C:18]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([O:28][CH3:29])[CH:22]=2)([CH3:20])[CH3:19])=[CH:16][N:17]=1)C(O)=O.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:45])C=CC=CC=1.CC[N:57]([CH:61](C)C)C(C)C.[CH3:64][C:65]([OH:68])([CH3:67])[CH3:66]>C1(C)C=CC=CC=1.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([NH:57][C:61](=[O:45])[O:68][C:65]([CH3:67])([CH3:66])[CH3:64])[CH:8]=[C:9]([F:37])[C:10]=1[CH2:11][S:12][C:13]1[N:14]([C:30]2[CH:31]=[CH:32][C:33]([F:36])=[CH:34][CH:35]=2)[C:15]([C:18]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([O:28][CH3:29])[CH:22]=2)([CH3:19])[CH3:20])=[CH:16][N:17]=1

참가 물질

7

반응물 4

HCID 6386tert-ButanolHCID 81531DiisopropylethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 667398303-chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluoro-phenyl)-1H-imidazol-2-ylthio)methyl)-5-fluorobenzoic acid

생성물 1

HCID 66741137tert-butyl 3-chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-5-fluorophenylcarbamate

시약·촉매·용매 2

HCID 1140Toluene용매HCID 8857Ethyl Acetate용매

반응 조건

온도
0 °C

실험 절차

To a suspension of 3-chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-5-fluorobenzoic acid (540 mg) in a mixture of toluene (5 mL) and t-BuOH (1.5 mL) cooled to 0° C. was added diphenyl phosphoryl azide (DPPA) (302 mg, 1.1 eq) followed by DIPEA (1.3 eq, 0.23 mL). During addition of base, white slurry became clear solution. Reaction mixture was heated at 80° C. overnight. LC-MS showed complete conversion. After cooling to ambient temperature, the reaction mixture was diluted with EtOAc and washed with satd NaHCO3. The organic layer was dried, concentrated and purified by chromatography (silica, EtOAc/Hex, 10-60%) to yield tert-butyl 3-chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-5-fluorophenylcarbamate (230 mg). MS (EI) m/z 634 (MH+).

후처리

  1. additionDuring addition of base, white slurry
  2. customReaction mixture
  3. temperaturewas heated at 80° C. overnight
  4. temperatureAfter cooling to ambient temperature
  5. washwashed with satd NaHCO3
  6. customThe organic layer was dried
  7. concentrationconcentrated
  8. custompurified by chromatography (silica, EtOAc/Hex, 10-60%)

출처 및 근거

ORD 기록
ord-dbb070e832f7431c90fc11139bfc57bf
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08785488B2

반응 노트

불러오는 중…