Trifluoroacetic acid → N-ethyl-N-[(2R)-2-(thiazol-5-ylmethoxycarbonylamino)-3-phenylpropyl]-N-[(2S)-2-(thiazol-5-ylmethoxycarbonylamino)-3-phenylpropyl]amine

HRID 39393

반응식

HRID 39393 반응식
C(OC([NH:8][C@H:9]([CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[CH2:10][N:11]([CH2:14][C@@H:15]([NH:23][C:24]([O:26][C:27](C)(C)[CH3:28])=[O:25])[CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH2:12][CH3:13])=O)(C)(C)C.FC(F)(F)C(O)=O.[C:45](=[O:63])([O:56][CH2:57][C:58]1[S:62][CH:61]=[N:60][CH:59]=1)OC1C=CC([N+]([O-])=O)=CC=1>ClCCl.C(OCC)(=O)C>[CH2:12]([N:11]([CH2:10][C@H:9]([NH:8][C:45]([O:56][CH2:57][C:58]1[S:62][CH:61]=[N:60][CH:59]=1)=[O:63])[CH2:31][C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1)[CH2:14][C@@H:15]([NH:23][C:24]([O:26][CH2:27][C:28]1[S:62][CH:61]=[N:60][CH:59]=1)=[O:25])[CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH3:13]

참가 물질

6

반응물 3

HCID 6422Trifluoroacetic acidHCID 98821474-Nitrophenyl 1,3-thiazol-5-ylmethyl carbonateHCID 60204747N-[(2R)-2-(tert-butoxycarbonylamino)-3-phenylpropyl]-N-[(2S)-2-(tert-butoxycarbonylamino)-3-phenylpropyl]-N-ethylamine

생성물 1

HCID 11854468N-ethyl-N-[(2R)-2-(thiazol-5-ylmethoxycarbonylamino)-3-phenylpropyl]-N-[(2S)-2-(thiazol-5-ylmethoxycarbonylamino)-3-phenylpropyl]amine수율 33.8%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

반응 조건

온도
60 °C

실험 절차

The product from Example 71B (86 mg, 0.17 mmol) in dichloromethane (1.8 mL) was treated with trifluoroacetic acid (1.0 mL) at ambient temperature. After stirring for 2 hours, the mixture was concentrated and treated with aqueous 10% K2CO3 (2.4 mL). The aqueous mixture was extracted with ethyl acetate (3×3 mL). The ethyl acetate extracts were combined and treated with 4-nitrophenyl 1,3-thiazol-5-ylmethyl carbonate [prepared from 4-nitrophenyl 1,3-thiazol-5-ylmethyl carbonate hydrochloride salt (99 mg, 0.35 mmol) by extraction with aqueous NaHCO3] in ethyl acetate (6 mL). After heat at 60° C. for 18 hours, the mixture was allowed to cool to ambient temperature and was concentrated. The residue was purified by flash column chromatography on silica gel eluting with (chloroform:methanol, 98:2) to provide the title compound (34.1 mg, 32%). 1H NMR (CDCl3) δ 8.78 (s, 2H), 7.85 (s, 2H), 7.32-7.05 (m, 10H), 5.40-5.17 (m, 6H), 4.20 (br s, 2H), 3.49-2.55 (m, 10H), 0.85 (t, 3H); MS (ESI+) m/z 594 (M+H)+.

후처리

  1. concentrationthe mixture was concentrated
  2. additiontreated with aqueous 10% K2CO3 (2.4 mL)
  3. extractionThe aqueous mixture was extracted with ethyl acetate (3×3 mL)
  4. temperatureto cool to ambient temperature
  5. concentrationwas concentrated
  6. customThe residue was purified by flash column chromatography on silica gel eluting with (chloroform:methanol, 98:2)

출처 및 근거

ORD 기록
ord-82e081cf2cd94283a4c1c1ce5a1b5d53
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08524753B2

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