Diphosgene → (2S,3S)-N-(4-acetyl-thiazol-2-yl)-2-[(R)-4-(4-methoxy-phenyl)-2,5-dioxo-imidazolidin-1-yl]-3-phenyl-butyramide

HRID 32809

반응식

HRID 32809 반응식
[C:1]([C:4]1[N:5]=[C:6]([NH:9][C:10](=[O:33])[C@@H:11]([NH:20][C:21](=[O:32])[C@H:22]([NH2:31])[C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)[C@H:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH3:13])[S:7][CH:8]=1)(=[O:3])[CH3:2].C(N(C(C)C)CC)(C)C.[O:43]=[C:44](Cl)OC(Cl)(Cl)Cl>O1CCCC1.C1(C)C=CC=CC=1.C(OCC)(=O)C>[C:1]([C:4]1[N:5]=[C:6]([NH:9][C:10](=[O:33])[C@@H:11]([N:20]2[C:21](=[O:32])[C@@H:22]([C:23]3[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=3)[NH:31][C:44]2=[O:43])[C@H:12]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH3:13])[S:7][CH:8]=1)(=[O:3])[CH3:2]

참가 물질

7

반응물 3

HCID 10426DiphosgeneHCID 81531DiisopropylethylamineHCID 86603380(2S,3S)-N-(4-acetyl-thiazol-2-yl)-2-[(R)-2-amino-2-(4-methoxy-phenyl)-acetylamino]-3-phenyl-butyramide

생성물 1

HCID 11648879(2S,3S)-N-(4-acetyl-thiazol-2-yl)-2-[(R)-4-(4-methoxy-phenyl)-2,5-dioxo-imidazolidin-1-yl]-3-phenyl-butyramide수율 119.8%

시약·촉매·용매 3

HCID 1140Toluene용매HCID 8028Tetrahydrofuran용매2회HCID 8857Ethyl Acetate용매

반응 조건

온도
0 °C

실험 절차

(2S,3S)-N-(4-Acetyl-thiazol-2-yl)-2-[(R)-2-amino-2-(4-methoxy-phenyl)-acetylamino]-3-phenyl-butyramide (2.7 g, 90% purity, 5.2 mmol) and diisopropylethylamine (4.2 mL, 23.6 mmol) in tetrahydrofuran (50 mL) were added to a solution of diphosgene (0.48 mL, 4 mmol) in a mixture of toluene (50 mL) and tetrahydrofuran (50 mL) over 10 minutes at 0° C. The mixture was stirred at 0° C. for 20 minutes and diluted with ethyl acetate. The mixture was washed with water, brine and dried (sodium sulfate). Evaporation of the solvents and chromatography of the residue over silica gel with 0.4-1% v/v methanol in dichloromethane gave (2S,3S)-N-(4-acetyl-thiazol-2-yl)-2-[(R)-4-(4-methoxy-phenyl)-2,5-dioxo-imidazolidin-1-yl]-3-phenyl-butyramide (2.36 g, 92%) as a white solid.

후처리

  1. washThe mixture was washed with water, brine
  2. dry with materialdried (sodium sulfate)
  3. customEvaporation of the solvents and chromatography of the residue over silica gel with 0.4-1% v/v methanol in dichloromethane

출처 및 근거

ORD 기록
ord-269506ebc9e54b1dac5e31a8e9d82d6e
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07427635B2

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