HCID 68872883, compound → HCID 68875972, compound

HRID 1435982Notes

Reaction equation

HRID 1435982 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([NH:14][C:15]2[CH:16]=[C:17]3[C:22](=[CH:23][CH:24]=2)[C:21]([NH2:25])=[N:20][CH:19]=[CH:18]3)[CH2:9]1)=O)(C)(C)C>ClCCl.FC(F)(F)C(O)=O>[NH:8]1[CH2:13][CH2:12][CH2:11][CH:10]([NH:14][C:15]2[CH:16]=[C:17]3[C:22](=[CH:23][CH:24]=2)[C:21]([NH2:25])=[N:20][CH:19]=[CH:18]3)[CH2:9]1

Participants

4

Reactant 1

HCID 68872883HCID 68872883, compound

Product 1

HCID 68875972HCID 68875972, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

To a degassed solution of 1-amino-6-bromoisoquinolin (554 mg), prepared as described in WO 98/47876 (Akzo Nobel N.V.), 3-aminopiperidine-1-carboxylic acid tert-butyl ester (823 mg), 2-(di-tert-butylphosphino)biphenyl and sodium tert-butoxide (367 mg) in dioxane (10 ml) under argon, was added tris(dibenzylidene-acetone)dipalladium(0). The mixture was further degassed with argon then heated at 120° C. for 90 minutes. The mixture was cooled to room temperature then diluted with methanol. The crude mixture was loaded onto a pre-acidified SCX column and the basic products eluted with 2M ammonia in methanol to give a crude residue (700 mg). The residue was purified by preparative HPLC to give 3-(1-aminoisoquinolin-6-ylamino)piperidin-1-carboxylic acid tert-butyl ester. A mixture of the 3-(1-aminoisoquinolin-6-ylamino)-piperidin-1-carboxylic acid tert-butyl ester in dichloromethane (6 ml) and trifluoroacetic acid (3 ml) were stirred at ambient temperature for 3 h. The mixture was concentrated then purified by preparative HPLC followed by loading onto a pre-acidified SCX column and the free base eluted with 2M ammonia in methanol to give 6-(piperidin-3-ylamino)-isoquinolin-1-ylamine, El-MS: m/z=243.7 [M+H]+.

Workup

  1. concentrationThe mixture was concentrated
  2. customthen purified by preparative HPLC
  3. washthe free base eluted with 2M ammonia in methanol

Sources & evidence

ORD record
ord-1b9fc6a7167e44188170621b2a35a1bc
Source dataset
uspto-grants-2009_11
Patent number
US07618985B2

Reaction notes

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