Hydrochloric Acid → 6-cyclopropyl-5-(6-(3,5-dimethylisoxazol-4-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-4-yl)nicotinonitrile

HRID 1773697Notes

Reaction equation

N[C:2]1[CH:3]=[C:4]([C:11]2[C:19]3[NH:18][C:17](=[O:20])[NH:16][C:15]=3[CH:14]=[C:13]([C:21]3[C:22]([CH3:27])=[N:23][O:24][C:25]=3[CH3:26])[CH:12]=2)[C:5]([CH:8]2[CH2:10][CH2:9]2)=[N:6][CH:7]=1.Cl.N([O-])=O.[Na+].C([O-])(O)=O.[Na+].[Cu][C:39]#[N:40].[C-]#N.[Na+]>O>[CH:8]1([C:5]2[C:4]([C:11]3[C:19]4[NH:18][C:17](=[O:20])[NH:16][C:15]=4[CH:14]=[C:13]([C:21]4[C:22]([CH3:27])=[N:23][O:24][C:25]=4[CH3:26])[CH:12]=3)=[CH:3][C:2]([C:39]#[N:40])=[CH:7][N:6]=2)[CH2:10][CH2:9]1

Participants

Conditions

Temperature: 70 °C

Procedure

4-(5-amino-2-cyclopropylpyridin-3-yl)-6-(3,5-dimethylisoxazol-4-yl)-1H-benzo[d]imidazol-2(3H)-one (21 mg, 0.058 mmol) was suspended in a mixture of water (1 mL) and con. HCl (1 mL), cooled suspension to 0° C., a solution of sodium nitrite (4 mg, 0.058 mmol) in water was added slowly. After 5 mins, the reaction mixture was neutralised by the addition of NaHCO3 solution. Then the resultant suspension was added in aliquots to a solution of copper (I) cyanide (5 mg, 0.058 mmol) and sodium cyanide (6 mg, 0.11 mmol) in water at room temperature. Heated to 70° C. for 30 mins. Extracted with EtOAc, evaporated organic solvent, the residue was purified with Prep HPLC. (0-100% CH3CN/H2O) to afford 1.2 mg of 6-cyclopropyl-5-(6-(3,5-dimethylisoxazol-4-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-4-yl)nicotinonitrile.

Workup

extractionExtracted with EtOAc
customevaporated organic solvent
customthe residue was purified with Prep HPLC

Sources & evidence

ORD record: ord-e41f5ebed340481fb4ab6c904c7e5984
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09255089B2

Reaction notes

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