Reaction #10649

Reaction equation

sodium hydrogencarbonate

Intermediate 90

4-chloro-5-aminoisoquinoline

tert-butyl 4-oxo-1-aminocyclohexylcarboxylate

sodium borohydride

→

title compound

N-(tert-butoxycarbonyl)-N′-(4-chloro-5-isoquinolyl)-1,4-cyclohexanediamine

Solvents

dichloromethane

methanol

Conditions

Workup

1. 1
   workup.STIRRINGstirred for 1.5 hours with ice cooling
2. 2
   Extractionextracted twice with ethyl acetate (15 ml for each time)
3. 3
   DryingThe organic layer was dried over anhydrous sodium sulfate
4. 4
   Otherthe solvent was evaporated under reduced pressure
5. 5
   OtherThe residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=1:1)

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).

Source