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 1180769ノート

反応式

HRID 1180769 の反応式
[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]

参加物

10

反応物 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

生成物 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)pentylcarbamate収率 98.2%

試薬・触媒・溶媒 4

HCID 1140Toluene溶媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-e7fbfbd0f2d34a368692cf53ba6b0f18
出典データセット
uspto-grants-2007_10
特許番号
US07282512B2

反応ノート

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