Sodium Bicarbonate → N-(tert-butoxycarbonyl)-N'-(4-chloro-5-isoquinolyl)-1,4-cyclohexanediamine

HRID 10553

Reaction equation

HRID 10553 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][C:17](C(OC(C)(C)C)=O)([NH2:20])[CH2:16][CH2:15]1.[BH4-].[Na+].[C:30](=[O:33])([O-])[OH:31].[Na+]>CC(C)[O-].CC(C)[O-].CC(C)[O-].CC(C)[O-].[Ti+4].CO.ClCCl>[C:6]([O:31][C:30]([NH:20][CH:17]1[CH2:16][CH2:15][CH:14]([NH:12][C:10]2[CH:9]=[CH:8][CH:7]=[C:6]3[C:11]=2[C:2]([Cl:1])=[CH:3][N:4]=[CH:5]3)[CH2:19][CH2:18]1)=[O:33])([CH3:11])([CH3:7])[CH3:5]

Participants

8

Reactant 4

HCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 219799374-Chloroisoquinolin-5-amineHCID 21979990Tert-butyl 4-oxo-1-aminocyclohexylcarboxylate

Product 1

HCID 21979991N-(tert-butoxycarbonyl)-N'-(4-chloro-5-isoquinolyl)-1,4-cyclohexanediamine

Reagents, catalysts & solvents 3

HCID 11026Titanium isopropoxideCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

According to the method of Example 103, Step A, a mixture of Intermediate 90 (100 mg), tert-butyl 4-oxo-1-aminocyclohexylcarboxylate (270 mg), titanium tetraisopropoxide (0.34 ml) and dichloromethane (7 ml) was stirred at room temperature for 120 hours. The reaction mixture was added with sodium borohydride (94 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 then 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 (40.4 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-2183330ad69d4daf8b0bf3debc9cee84
Source dataset
uspto-grants-2006_08
Patent number
US07094789B2

Linked notes

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