Sodium Chloride → {1-[(4-phenyl-1,3-thiazol-2-yl)methyl]cyclobutyl}methyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamate

HRID 1180769노트

반응식

HRID 1180769 반응식
[C:1]1([C:7]2[N:8]=[C:9]([CH2:12][C:13]3([CH2:17][OH:18])[CH2:16][CH2:15][CH2:14]3)[S:10][CH:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:19](Cl)(Cl)=[O:20].[NH2:23][C@@H:24]([CH2:38][CH2:39][CH2:40][CH3:41])[CH:25]([OH:37])[C:26]([NH:28][C@@H:29]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[CH3:30])=[O:27].C(N(CC)C(C)C)(C)C.[Cl-].[Na+]>ClCCl.C1(C)C=CC=CC=1.O1CCCC1.C(OCC)(=O)C>[OH:37][CH:25]([C@@H:24]([NH:23][C:19](=[O:20])[O:18][CH2:17][C:13]1([CH2:12][C:9]2[S:10][CH:11]=[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[N:8]=2)[CH2:16][CH2:15][CH2:14]1)[CH2:38][CH2:39][CH2:40][CH3:41])[C:26](=[O:27])[NH:28][C@@H:29]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[CH3:30]

참가 물질

10

반응물 5

HCID 5234Sodium ChlorideHCID 6371PhosgeneHCID 81531DiisopropylethylamineHCID 11265560(3S)-3-amino-2-hydroxy-N-[(1R)-1-phenylethyl]heptanamideHCID 11737047{1-[(4-Phenyl-1,3-thiazol-2-yl)methyl]cyclobutyl}methanol

생성물 1

HCID 11753176{1-[(4-phenyl-1,3-thiazol-2-yl)methyl]cyclobutyl}methyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamate수율 98.2%

시약·촉매·용매 4

HCID 1140Toluene용매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 0.16 g (0.63 mmol) of {1-[(4-phenyl-1,3-thiazol-2-yl)methyl]cyclobutyl}methanol in 2 mL of dichloromethane (cooled to 0° C. was added a 1.0 M solution of 0.94 mL (1.41 mmol) of phosgene in toluene and the contents stirred for 16 h. The reaction mixture was concentrated and the residue was dissolved in 3 mL of tetrahydrofuran and added to a 0° C. solution of 0.165 g (0.63 mmol) of (3S)-3-amino-2-hydroxy-N-[(1R)-1-phenylethyl]heptanamide and 0.325 mL (1.89 mmol) of N,N-diisopropylethylamine in 2 mL of tetrahydrofuran. After stirring for 7 h, 30 mL of ethyl acetate and 20 mL of saturated sodium chloride were added. The organic phase was isolated, dried using magnesium sulfate, and concentrated under vacuum to afford the crude product, which was purified by silica gel chromatography using ethyl acetate:hexane (1:1) as the eluent to afford 0.34 g (98%) of {1-[(4-phenyl-1,3-thiazol-2-yl)methyl]cyclobutyl}methyl(1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamate as a colorless oil. 1H NMR (300 MHz, CDCl3) δ 7.90, 7.92 (2s, 1H), 7.46-7.18 (m, 10 H), 5.61 (d, J=9 Hz, 1H), 5.14-5.01 (m, 2H), 4.19-4.06 (m, 4H), 3.88 (m, 1H), 3.23 (s, 2H), 2.21-1.50 (m, 10 H), 1.46 (d, J=7 Hz, 3H), 1.37-1.27 (m, 2H), 0.94 (m, 3H). LC-MS m/z 550 (M+H).

후처리

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionthe residue was dissolved in 3 mL of tetrahydrofuran
  3. stirringAfter stirring for 7 h
  4. customThe organic phase was isolated
  5. customdried
  6. concentrationconcentrated under vacuum
  7. customto afford the crude product, which
  8. customwas purified by silica gel chromatography

출처 및 근거

ORD 기록
ord-e7fbfbd0f2d34a368692cf53ba6b0f18
출처 데이터셋
uspto-grants-2007_10
특허 번호
US07282512B2

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