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

HRID 1455603노트

반응식

HRID 1455603 반응식
Cl.[NH2:2][C@@:3]([CH3:9])([CH2:6][CH2:7][CH3:8])[CH2:4][OH:5].[F:10][C:11]([F:33])([CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH2:12][C@H:13]([NH:17][C:18]([N:20]1[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1)=[O:19])[C:14](O)=[O:15].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>[F:33][C:11]([F:10])([CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH2:12][C@H:13]([NH:17][C:18]([N:20]1[CH2:21][CH2:22][O:23][CH2:24][CH2:25]1)=[O:19])[C:14](=[O:15])[NH:2][C@@:3]([CH2:4][OH:5])([CH3:9])[CH2:6][CH2:7][CH3:8]

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 86607351(S)-2-amino-2-methyl-pentan-1-ol hydrochloride

생성물 1

HCID 86607350morpholine-4-carboxylic acid [(S)-3,3-difluoro-1-((S)-1-hydroxymethyl-1-methyl-butylcarbamoyl)-4-phenyl-butyl]-amide수율 75.4%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

A mixture of (S)-2-amino-2-methyl-pentan-1-ol hydrochloride (104.4 mg, 0.67 mmol), (S)-4,4-difluoro-2-[(morpholine-4-carbonyl)-amino]-5-phenyl-pentanoic acid (231 mg, 0.67 mmol), EDCI (154 mg, 0.8 mmol), HOBT (108 mg, 0.8 mmol) and Diisopropyl ethylamine (0.23 mL) in DMF (2 mL) 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 MgSO4 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)-3,3-difluoro-1-((S)-1-hydroxymethyl-1-methyl-butylcarbamoyl)-4-phenyl-butyl]-amide (223 mg, 75%).

후처리

  1. washwashed with cold 1N HCl, saturated NaHCO3
  2. dry with materialThe organic phase is dried over MgSO4 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-b0cdd4d63746428d83aef298ac799755
출처 데이터셋
uspto-grants-2009_01
특허 번호
US07482448B2

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