Phosgene → HCID 58979648、化合物

HRID 1180748ノート

反応式

HRID 1180748 の反応式
[CH2:1]([C:8]1([CH2:14][OH:15])[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:16](Cl)(Cl)=[O:17].Cl.[NH2:21][C@H:22]([CH:36]([OH:48])[C:37](=[O:47])[NH:38][C@@H:39]([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[CH3:40])[CH2:23][CH2:24][CH2:25][CH2:26][NH:27][C:28]([N:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1)=[O:29].C(N(CC)CC)C>O1CCCC1.C1(C)C=CC=CC=1.CO>[OH:48][CH:36]([C@@H:22]([NH:21][C:16](=[O:17])[O:15][CH2:14][C:8]1([CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1)[CH2:23][CH2:24][CH2:25][CH2:26][NH:27][C:28]([N:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1)=[O:29])[C:37](=[O:47])[NH:38][C@@H:39]([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[CH3:40]

参加物

8

反応物 4

HCID 6371PhosgeneHCID 8471TriethylamineHCID 58979707(1-Benzylcyclohexyl)methanolHCID 69236903N-((5S)-5-amino-6-hydroxy-7-oxo-7-{[(1R)-1-phenylethyl]amino}heptyl)-4-morpholinecarboxamide hydrochloride

生成物 1

HCID 58979648HCID 58979648、化合物収率 57%

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 1140Toluene溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 63 mg (0.31 mmol) of (1-benzylcyclohexyl)methanol in 1 mL of tetrahydrofuran was added 0.32 mL (0.62 mmol) of 1.93 M phosgene in toluene. The reaction was stirred at room temperature for 18 h, quenched with a stream of nitrogen gas for 5 min, and concentrated under reduced pressure. The resulting liquid was added to a solution of 133 mg (0.31 mmol) of N-((5S)-5-amino-6-hydroxy-7-oxo-7-{[(1R)-1-phenylethyl]amino}heptyl)-4-morpholinecarboxamide hydrochloride and 0.095 mL (0.68 mmol) of triethylamine in 2 mL of methanol. The reaction was stirred at room temperature for 24 h and concentrated under reduced pressure. The residue was purified by silica chromatography eluting with 6:4 acetone:hexanes to afford 110 mg (57%) of (1-benzylcyclohexyl)methyl(1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)-5-[(4-morpholinylcarbonyl)amino]pentylcarbamate. 1H NMR (400 MHz, DMSO-d6) δ 7.96 (m, 1H), 7.06-7.29 (m, 10H), 6.53 (d, J=9 Hz, 1H), 6.41 (m, 1H), 5.56-5.75 (m, 1H), 4.88 (qnt, J=7 Hz, 1H), 3.88 (m, 1H), 3.73 (m, 1H), 3.51 (m, 2H), 3.45 (t, J=4 Hz, 4H), 3.16 (t, J=4 Hz, 4H), 2.96 (m, 2H), 2.57 (s, 2H), 1.17-1.54 (m, 19H). ES-LCMS m/z 645 (M+Na).

後処理

  1. customquenched with a stream of nitrogen gas for 5 min
  2. concentrationconcentrated under reduced pressure
  3. stirringThe reaction was stirred at room temperature for 24 h
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica chromatography
  6. washeluting with 6:4 acetone

出典と根拠

ORDレコード
ord-c6590bde8d7a47498329f882ebb990ac
出典データセット
uspto-grants-2007_10
特許番号
US07282512B2

反応ノート

読み込み中…