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4-Methylmorpholine → 9-Fluoro-5-(2-hydroxyethyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]diazepine-1-carboxylic acid 2-methyl-4-(2,3,4,5-tetrahydrobenzo[b]azepine-1-carbonyl)benzylamide

HRID 558952
ノート
印刷プレビュー

反応式

HRID 558952 の反応式
[F:1][C:2]1[C:12]2[N:11]([C:13](=[O:36])[NH:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([C:22]([N:24]4[CH2:30][CH2:29][CH2:28][CH2:27][C:26]5[CH:31]=[CH:32][CH:33]=[CH:34][C:25]4=5)=[O:23])=[CH:18][C:17]=3[CH3:35])[CH2:10][CH2:9][C:8](=[O:37])[N:7]([CH2:38][C:39](O)=[O:40])[C:6]=2[CH:5]=[CH:4][CH:3]=1.CN1CCOCC1.[BH4-].[Na+].[Cl-].[NH4+]>C1COCC1.O>[CH3:35][C:17]1[CH:18]=[C:19]([C:22]([N:24]2[CH2:30][CH2:29][CH2:28][CH2:27][C:26]3[CH:31]=[CH:32][CH:33]=[CH:34][C:25]2=3)=[O:23])[CH:20]=[CH:21][C:16]=1[CH2:15][NH:14][C:13]([N:11]1[CH2:10][CH2:9][C:8](=[O:37])[N:7]([CH2:38][CH2:39][OH:40])[C:6]2[CH:5]=[CH:4][CH:3]=[C:2]([F:1])[C:12]1=2)=[O:36]
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 79724-MethylmorpholineHCID 25517Ammonium ChlorideHCID 4311764Sodium borohydrideHCID 11699686{6-Fluoro-5-[2-methyl-4-(2,3,4,5-tetrahydrobenzo[b]azepine-1-carbonyl)benzylcarbamoyl]-2-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]diazepin-1-yl}-acetic acid

生成物 1

HCID 115195689-Fluoro-5-(2-hydroxyethyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]diazepine-1-carboxylic acid 2-methyl-4-(2,3,4,5-tetrahydrobenzo[b]azepine-1-carbonyl)benzylamide

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of {6-fluoro-5-[2-methyl-4-(2,3,4,5-tetrahydrobenzo[b]azepine-1-carbonyl)benzylcarbamoyl]-2-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]diazepin-1-yl}acetic acid from Example 2 (170 mg, 0.30 mmol) in THF (6 ml) were added N-methylmorpholine (47 μl, 0.43 mmol) and isobutyl chlroroformate (57 μl, 0.43 mmol) while cooling in an ice/water bath. The mixture was stirred for 1 h, filtered and added to a solution of sodium borohydride (27 mg, 0.70 mmol) in water (1.5 ml) while cooling in an ice/water bath. The mixture was allowed to warm to room temperature slowly and stirred for 2 h. Saturated ammonium chloride solution (2 ml) was added and the mixture evaporated in vacuo. The residue was partitioned between choroform and water and the organic layer was washed with brine, dried over magnesium sulphate and evaporated in vacuo. The residue was purified by flash chromatography on silica (eluant methanol:dichloromethane 6:94) to give a white solid; yield 104 mg, 64%.

後処理

  1. temperaturewhile cooling in an ice/water bath
  2. filtrationfiltered
  3. temperaturewhile cooling in an ice/water bath
  4. stirringstirred for 2 h
  5. customthe mixture evaporated in vacuo
  6. customThe residue was partitioned between choroform and water
  7. washthe organic layer was washed with brine
  8. dry with materialdried over magnesium sulphate
  9. customevaporated in vacuo
  10. customThe residue was purified by flash chromatography on silica (eluant methanol:dichloromethane 6:94)
  11. customto give a white solid

出典と根拠

ORDレコード
ord-a316d339508643829dbe890e0b3d972a
出典データセット
uspto-grants-2011_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08063038B2

反応ノート

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