Diisopropylethylamine → ((S)-1-{2-[3-Methoxy-4-(4-methyl-imidazol-1-yl)-phenylamino]-thiazol-4-yl}-3-methyl-butyl)-carbamic acid tert-butyl ester

HRID 604894노트

반응식

HRID 604894 반응식
[C:1]([O:5][C:6](=[O:17])[NH:7][C@H:8]([C:13](=O)[CH2:14]Br)[CH2:9][CH:10]([CH3:12])[CH3:11])([CH3:4])([CH3:3])[CH3:2].C(N(CC)C(C)C)(C)C.[CH3:27][O:28][C:29]1[CH:30]=[C:31]([NH:41][C:42]([NH2:44])=[S:43])[CH:32]=[CH:33][C:34]=1[N:35]1[CH:39]=[C:38]([CH3:40])[N:37]=[CH:36]1>>[C:1]([O:5][C:6](=[O:17])[NH:7][C@H:8]([C:13]1[N:44]=[C:42]([NH:41][C:31]2[CH:32]=[CH:33][C:34]([N:35]3[CH:39]=[C:38]([CH3:40])[N:37]=[CH:36]3)=[C:29]([O:28][CH3:27])[CH:30]=2)[S:43][CH:14]=1)[CH2:9][CH:10]([CH3:12])[CH3:11])([CH3:4])([CH3:3])[CH3:2]

참가 물질

4

반응물 3

HCID 81531DiisopropylethylamineHCID 11034179Tert-butyl N-[(3S)-1-bromo-5-methyl-2-oxohexan-3-YL]carbamateHCID 71650841[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]thiourea

생성물 1

HCID 86624688((S)-1-{2-[3-Methoxy-4-(4-methyl-imidazol-1-yl)-phenylamino]-thiazol-4-yl}-3-methyl-butyl)-carbamic acid tert-butyl ester

실험 절차

The title compound was prepared in analogy to example 1 step e) from 102 mg (0.33 mmol) (S)-[1-(2-bromo-acetyl)-3-methyl-butyl]-carbamic acid tert-butyl ester, 42 mg (0.33 mmol) N,N-diisopropyl ethyl amine and 79 mg (0.3 mmol) [3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-thiourea. The crude reaction was poured onto water and extracted twice with ethyl acetate. The organic layer was washed with brine, dried over sodium sulphate, filtered and the solvent was evaporated under vacuo. The crude product was purified on silica gel with methylene chloride/methanol 19/1 yielding 97 mg (69%) ((S)-1-{2-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenylamino]-thiazol-4-yl}-3-methyl-butyl)-carbamic acid tert-butyl ester as a light yellow solid. MS ISP (m/e): 472.3 (100) (M+H)+. 1H NMR (DMSO-D6, 250 MHz): δ (ppm)=10.35 (s, 1H), 7.95 (s, 1H), 7.65 (s, 1H), 7.23 (d, 1H), 7.15 (d, 1H), 7.03 (s, 1H), 6.99 (d, 1H), 6.55 (s, 1H), 4.59 (m, 1H), 3.82 (s, 3H), 2.14 (s, 3H), 1.70-1.55 (m, 3H), 1.39 (s, 9H), 0.90 (s, 6H). α589=−43.2; T=20° C.; c=1 g/m100 ml, solvent=MeOH.

후처리

  1. customThe crude reaction
  2. additionwas poured onto water
  3. extractionextracted twice with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. customthe solvent was evaporated under vacuo
  8. customThe crude product was purified on silica gel with methylene chloride/methanol 19/1 yielding 97 mg (69%) ((S)-1-{2-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenylamino]-thiazol-4-yl}-3-methyl-butyl)-carbamic acid tert-butyl ester as a light yellow solid
  9. customT=20° C.

출처 및 근거

ORD 기록
ord-84cf3baca01f43ac83e3cb0ed883f8c9
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07910740B2

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