1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → morpholine-4-carboxylic acid {(S)-1-[(S)-1-(benzoxazole-2-carbonyl)-1-methyl-butylcarbamoyl]-3,3-difluoro-4-phenyl-butyl}-amide

HRID 1455602노트

반응식

HRID 1455602 반응식
Cl.[NH2:2][C@@:3]([CH3:18])([CH2:15][CH2:16][CH3:17])[C:4]([C:6]1[O:7][C:8]2[CH:14]=[CH:13][CH:12]=[CH:11][C:9]=2[N:10]=1)=[O:5].[F:19][C:20]([F:42])([CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[CH2:21][C@H:22]([NH:26][C:27]([N:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1)=[O:28])[C:23](O)=[O:24].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C>CN(C=O)C.C(OCC)(=O)C>[O:7]1[C:8]2[CH:14]=[CH:13][CH:12]=[CH:11][C:9]=2[N:10]=[C:6]1[C:4]([C@:3]([NH:2][C:23]([C@@H:22]([NH:26][C:27]([N:29]1[CH2:30][CH2:31][O:32][CH2:33][CH2:34]1)=[O:28])[CH2:21][C:20]([F:42])([F:19])[CH2:35][C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1)=[O:24])([CH3:18])[CH2:15][CH2:16][CH3:17])=[O:5]

참가 물질

8

반응물 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 57535341(S)-4,4-Difluoro-2-[(morpholine-4-carbonyl)-amino]-5-phenyl-pentanoic acidHCID 68825022(S)-2-amino-1-benzoxazol-2-yl-2-methyl-pentan-1-one hydrochloride

생성물 1

HCID 11467060morpholine-4-carboxylic acid {(S)-1-[(S)-1-(benzoxazole-2-carbonyl)-1-methyl-butylcarbamoyl]-3,3-difluoro-4-phenyl-butyl}-amide수율 82%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

A mixture of (S)-2-amino-1-benzoxazol-2-yl-2-methyl-pentan-1-one hydrochloride (80.6 mg, 0.3 mmol), (S)-4,4-difluoro-2-[(morpholine-4-carbonyl)-amino]-5-phenyl-pentanoic acid (0.102 mg, 0.3 mmol), EDCI (69 mg, 0.36 mmol), HOBT (48.6 mg, 0.36 mmol) and Diisopropyl ethylamine (0.2 mL) in DMF is stirred at room temperature overnight. The reaction mixture is diluted with ethyl acetate, washed with cold 1N HCl, saturated NaHCO3 and then saturated NaCl solution. The organic phase is dried over magnesium sulfate and solvent evaporated under reduced pressure to give the crude product. Purification by Silica gel column chromatography, eluting with ethyl acetate and heptane mixture gives morpholine-4-carboxylic acid {(S)-1-[(S)-1-(benzoxazole-2-carbonyl)-1-methyl-butylcarbamoyl]-3,3-difluoro-4-phenyl-butyl}-amide (82%).

후처리

  1. washwashed with cold 1N HCl, saturated NaHCO3
  2. dry with materialThe organic phase is dried over magnesium sulfate and solvent
  3. customevaporated under reduced pressure
  4. customto give the crude product
  5. customPurification by Silica gel column chromatography
  6. washeluting with ethyl acetate and heptane mixture

출처 및 근거

ORD 기록
ord-7d77a191afcc404e8294baef144e17e9
출처 데이터셋
uspto-grants-2009_01
특허 번호
US07482448B2

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