Sodium Chloride → (1-{[(1-methyl-1H-imidazol-2-yl)sulfanyl]methyl}cyclobutyl)methyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamate

HRID 1180772

反応式

HRID 1180772 の反応式
[CH3:1][N:2]1[CH:6]=[CH:5][N:4]=[C:3]1[S:7][CH2:8][C:9]1([CH2:13][OH:14])[CH2:12][CH2:11][CH2:10]1.[C:15](Cl)(Cl)=[O:16].[NH2:19][C@@H:20]([CH2:34][CH2:35][CH2:36][CH3:37])[CH:21]([OH:33])[C:22]([NH:24][C@@H:25]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH3:26])=[O:23].C(N(CC)C(C)C)(C)C.[Cl-].[Na+]>ClCCl.C1(C)C=CC=CC=1.O1CCCC1.C(OCC)(=O)C>[OH:33][CH:21]([C@@H:20]([NH:19][C:15](=[O:16])[O:14][CH2:13][C:9]1([CH2:8][S:7][C:3]2[N:2]([CH3:1])[CH:6]=[CH:5][N:4]=2)[CH2:10][CH2:11][CH2:12]1)[CH2:34][CH2:35][CH2:36][CH3:37])[C:22](=[O:23])[NH:24][C@@H:25]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH3:26]

参加物

10

反応物 5

HCID 5234Sodium ChlorideHCID 6371PhosgeneHCID 81531DiisopropylethylamineHCID 11265560(3S)-3-amino-2-hydroxy-N-[(1R)-1-phenylethyl]heptanamideHCID 11435800(1-{[(1-methyl-1H-imidazol-2-yl)sulfanyl]methyl}cyclobutyl)methanol

生成物 1

HCID 11397962(1-{[(1-methyl-1H-imidazol-2-yl)sulfanyl]methyl}cyclobutyl)methyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamate収率 70%

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 0.132 g (0.625 mmol) of (1-{[(1-methyl-1H-imidazol-2-yl)sulfanyl]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 were 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 6 h, 30 mL of ethyl acetate and 20 mL of saturated sodium chloride was 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 eluting with ethyl acetate to afford 0.220 g (70%) of (1-{[(1-methyl-1H-imidazol-2-yl)sulfanyl]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 7.63-7.52 (m, 1H), 7.41 (m, 1H), 7.39-7.15 (m, 5H), 6.91, 6.98 (2s, 1H), 6.03 (br s, 1H), 5.69 (m, 1H), 5.19-5.11 (m, 1H), 4.18-3.95 (m, 4H), 3.61, 3.63 (2s, 2H), 3.28 (m, 2H), 2.21-1.61 (m, 10H), 1.60-1.16 (m, 5H), 0.90 (m, 3H). LC-MS m/z 503 (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 6 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
  9. washeluting with ethyl acetate

出典と根拠

ORDレコード
ord-3feacce7c9fb4b0e939f4645d1eb37c2
出典データセット
uspto-grants-2007_10
特許番号
US07282512B2

関連ノート

読み込み中…