Sodium Bicarbonate → 4-(4-Chloro-5-isoquinolyl)amino-1-(tert-butoxycarbonyl)piperidine

HRID 10551

反応式

HRID 10551 の反応式
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[NH2:12])[CH:5]=[N:4][CH:3]=1.O=[C:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1.[BH4-].[Na+].C(=O)([O-])O.[Na+]>CC(C)[O-].CC(C)[O-].CC(C)[O-].CC(C)[O-].[Ti+4].CO.ClCCl>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[NH:12][CH:14]2[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]2)[CH:5]=[N:4][CH:3]=1

参加物

8

反応物 4

HCID 516892Sodium BicarbonateHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 4311764Sodium borohydrideHCID 219799374-Chloroisoquinolin-5-amine

生成物 1

HCID 219798504-(4-Chloro-5-isoquinolyl)amino-1-(tert-butoxycarbonyl)piperidine収率 21.8%

試薬・触媒・溶媒 3

HCID 11026Titanium isopropoxide触媒HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒

実験手順

According to the method of Example 103, Step A, a mixture of Intermediate 90 (121 mg), tert-butyl 4-oxo-1-piperidinecarboxylate (274 mg), titanium tetraisopropoxide (0.41 ml) and dichloromethane (7 ml) was stirred at room temperature for 138 hours. The reaction mixture was added with sodium borohydride (114 mg) and methanol (1 ml) and stirred for 1.5 hours with ice cooling. The reaction mixture was added with saturated aqueous sodium hydrogencarbonate (10 ml) with ice cooling and extracted twice with ethyl acetate (15 ml for each time). The organic layer was dried over anhydrous sodium sulfate, and then the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=1:1) to obtain the title compound (53.5 mg).

後処理

  1. stirringstirred for 1.5 hours with ice cooling
  2. extractionextracted twice with ethyl acetate (15 ml for each time)
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=1:1)

出典と根拠

ORDレコード
ord-72438e154c334ea6b03363a7903a683d
出典データセット
uspto-grants-2006_08
特許番号
US07094789B2

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