Water → 4-{[(1S,2R)-2-(cyanoamino)cyclohexyl]amino}-N-(2-methoxyethyl)-6-methylquinazolin-2-carboxamide

HRID 1971138Notes

Reaction equation

HRID 1971138 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@@H:3]1[NH:8][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([CH3:19])[CH:17]=2)[N:12]=[C:11]([C:20]([NH:22][CH2:23][CH2:24][O:25][CH3:26])=[O:21])[N:10]=1.[N:27]#[C:28]Br.O>O1CCCC1.C(N(CC)CC)C>[C:28]([NH:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@@H:3]1[NH:8][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([CH3:19])[CH:17]=2)[N:12]=[C:11]([C:20]([NH:22][CH2:23][CH2:24][O:25][CH3:26])=[O:21])[N:10]=1)#[N:27]

Participants

6

Reactant 3

HCID 962WaterHCID 10476Cyanogen BromideHCID 687002114-{[(1S,2R)-2-aminocyclohexyl]amino}-N-(2-methoxyethyl)-6-methylquinazolin-2-carboxamide

Product 1

HCID 866384014-{[(1S,2R)-2-(cyanoamino)cyclohexyl]amino}-N-(2-methoxyethyl)-6-methylquinazolin-2-carboxamideYield 55.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

In an argon atmosphere, to a solution of 3.30 g of 4-{[(1S,2R)-2-aminocyclohexyl]amino}-N-(2-methoxyethyl)-6-methylquinazolin-2-carboxamide in 80 ml of tetrahydrofuran, 1.54 ml of triethylamine and 978 mg of cyanogen bromide were sequentially added at −20° C., and the mixture was stirred at the same temperature for 0.5 hour. Water was added to the reaction solution, and the mixture was subjected to an extraction with ethyl acetate. The organic layer was washed with water and saturated brine and dried over magnesium sulfate. The solvent was distilled off, and the residue was purified by silica gel column chromatography (chloroform:methanol=50:1), whereby 1.96 g of a desired compound was obtained as a pale yellow crystal.

Workup

  1. extractionthe mixture was subjected to an extraction with ethyl acetate
  2. washThe organic layer was washed with water and saturated brine
  3. dry with materialdried over magnesium sulfate
  4. distillationThe solvent was distilled off
  5. customthe residue was purified by silica gel column chromatography (chloroform:methanol=50:1)

Sources & evidence

ORD record
ord-6829e62e9fb848958a52a8090671eafb
Source dataset
uspto-grants-2013_04
Patent number
US08431586B2

Reaction notes

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