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

HRID 10551

Reaction equation

HRID 10551 reaction equation
[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

Participants

8

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 11026Titanium isopropoxideCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-72438e154c334ea6b03363a7903a683d
Source dataset
uspto-grants-2006_08
Patent number
US07094789B2

Linked notes

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