Dimethylformamide → HCID 178523379, compound

HRID 245740Notes

Reaction equation

[CH2:1]([O:8][C:9](=[O:29])[NH:10][CH2:11][C@H:12]1[CH2:17][CH2:16][C@H:15]([C:18](=O)[NH:19][CH2:20][C:21]2[C:26]([Cl:27])=[N:25][CH:24]=[CH:23][N:22]=2)[CH2:14][CH2:13]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P(Cl)(Cl)(Cl)=O.CN(C)C=O>C(#N)C>[CH2:1]([O:8][C:9](=[O:29])[NH:10][CH2:11][C@H:12]1[CH2:17][CH2:16][C@H:15]([C:18]2[N:22]3[CH:23]=[CH:24][N:25]=[C:26]([Cl:27])[C:21]3=[CH:20][N:19]=2)[CH2:14][CH2:13]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To benzyl((trans)-4-((3-chloropyrazin-2-yl)methylcarbamoyl)cyclohexyl)methylcarbamate (8.79 g, 18.98 mmol) in acetonitrile (anhydrous) (90 ml) were added phosphorus oxychloride (5.31 ml, 56.9 mmol) and N,N-dimethylformamide (a drop) and the mixture was stirred at 60° C. overnight. Then the mixture was concentrated, the residue was dissolved in dichloromethane and quenched with an excess of 7M ammonia in methanol. This mixture was concentrated again and the residue was purified by column chromatography (silica gel, dichloromethane with gradient 0 to 5% of methanol) to yield benzyl((trans)-4-(8-chloroimidazo[1,5-a]pyrazin-3-yl)cyclohexyl)methylcarbamate (6.58 g).

Workup

concentrationThen the mixture was concentrated
dissolutionthe residue was dissolved in dichloromethane
customquenched with an excess of 7M ammonia in methanol
concentrationThis mixture was concentrated again
customthe residue was purified by column chromatography (silica gel, dichloromethane with gradient 0 to 5% of methanol)

Sources & evidence

ORD record: ord-9992c9122a804a1788a6f94e6aa1e312
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08658794B2

Reaction notes

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