Sodium Chloride → (1-{[(2-chloro-4-pyrimidinyl)oxy]methyl}cyclobutyl)methyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamate

HRID 1180774

反応式

HRID 1180774 の反応式
[Cl:1][C:2]1[N:7]=[C:6]([O:8][CH2:9][C:10]2([CH2:14][OH:15])[CH2:13][CH2:12][CH2:11]2)[CH:5]=[CH:4][N:3]=1.[C:16](Cl)(Cl)=[O:17].[NH2:20][C@@H:21]([CH2:35][CH2:36][CH2:37][CH3:38])[CH:22]([OH:34])[C:23]([NH:25][C@@H:26]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH3:27])=[O:24].C(N(CC)C(C)C)(C)C.[Cl-].[Na+]>ClCCl.C1(C)C=CC=CC=1.O1CCCC1.C(OCC)(=O)C>[OH:34][CH:22]([C@@H:21]([NH:20][C:16](=[O:17])[O:15][CH2:14][C:10]1([CH2:9][O:8][C:6]2[CH:5]=[CH:4][N:3]=[C:2]([Cl:1])[N:7]=2)[CH2:13][CH2:12][CH2:11]1)[CH2:35][CH2:36][CH2:37][CH3:38])[C:23](=[O:24])[NH:25][C@@H:26]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH3:27]

参加物

10

反応物 5

HCID 5234Sodium ChlorideHCID 6371PhosgeneHCID 81531DiisopropylethylamineHCID 11265560(3S)-3-amino-2-hydroxy-N-[(1R)-1-phenylethyl]heptanamideHCID 11413552(1-{[(2-Chloro-4-pyrimidinyl)oxy]methyl}cyclobutyl)methanol

生成物 1

HCID 11489253(1-{[(2-chloro-4-pyrimidinyl)oxy]methyl}cyclobutyl)methyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamate収率 828.5%

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 0.106 g (0.05 mmol) of (1-{[(2-chloro-4-pyrimidinyl)oxy]methyl}cyclobutyl)methanol in 2 mL of dichloromethane cooled to 0° C. was added a 1.0 M solution of 0.937 mL (0.75 mmol) of phosgene in toluene and the contents stirred for 16 h. The reaction mixture was concentrated and the residue was dissolved in 4 mL of tetrahydrofuran and added to a 0° C. solution of 0.132 g (0.50 mmol) of (3S)-3-amino-2-hydroxy-N-[(1R)-1-phenylethyl]heptanamide and 0.259 mL (1.5 mmol) of N,N-diisopropylethylamine in 2 mL of tetrahydrofuran. After stirring for 5 h, ethyl acetate and saturated sodium chloride were added. The organic phase was isolated, dried using magnesium sulfate, concentrated under vacuum, and the residue was purified by silica gel chromatography eluting with ethyl acetate:hexane (7:3) to afford 0.215 g (89%) of (1-{[(2-chloro-4-pyrimidinyl)oxy]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 8.29 (d, J=6 Hz, 1H), 7.32-7.10 (m, 6H), 6.67 (d, J=6 Hz, 1H), 5.61-5.53 (m, 1H), 5.13-5.08 (m, 1H), 4.79, 4.89 (2d, J=5, 6 Hz, 1H), 4.36, 4.39 (2s, 2H), 4.38-4.18 (m, 3H), 3.84 (m, 1H), 2.07-1.50 (m, 10 H), 1.47-1.26 (m, 5H), 0.88 (m, 3H). LC-MS m/z 519 (M+H).

後処理

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionthe residue was dissolved in 4 mL of tetrahydrofuran
  3. stirringAfter stirring for 5 h
  4. customThe organic phase was isolated
  5. customdried
  6. concentrationconcentrated under vacuum
  7. customthe residue was purified by silica gel chromatography
  8. washeluting with ethyl acetate:hexane (7:3)

出典と根拠

ORDレコード
ord-a7ca0f1c4b104f2aa1806a97b1e03648
出典データセット
uspto-grants-2007_10
特許番号
US07282512B2

関連ノート

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