Dimethylformamide → 7-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)-3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine

HRID 62477Notes

Reaction equation

O=P(Cl)(Cl)Cl.[Cl:6][C:7]1[C:8]([CH2:13][NH:14][C:15]([CH:17]2[CH2:22][CH2:21][N:20]3[C:23]([C:26]([F:29])([F:28])[F:27])=[N:24][N:25]=[C:19]3[CH2:18]2)=O)=[N:9][CH:10]=[CH:11][N:12]=1.CN(C=O)C.C([O-])([O-])=O.[Na+].[Na+]>CC#N>[Cl:6][C:7]1[C:8]2[N:9]([C:15]([CH:17]3[CH2:22][CH2:21][N:20]4[C:23]([C:26]([F:29])([F:28])[F:27])=[N:24][N:25]=[C:19]4[CH2:18]3)=[N:14][CH:13]=2)[CH:10]=[CH:11][N:12]=1

Participants

Conditions

Temperature: 70 °C

Procedure

POCl3 (1.7 g, 11.09 mmol) was added dropwise to a solution of N-((3-chloropyrazin-2-yl)methyl)-3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-7-carboxamide (800 mg, 2.218 mmol) in CH3CN (4.4 mL) at 0° C., then DMF (0.11 mL) was added dropwise for 5 minutes at 0° C. The reaction was heated at 70° C. for overnight The reaction was poured into ice-water, then neutralized with aq. Na2CO3 to adjust to pH=8. The resulting mixture was extracted with DCM and the combined organic layer was washed with water, brine and dried over anhydrous Na2SO4. The organic layer was concentrated in vacuo and the residue was purified by silica gel column chromatography (DCM/THF=100/20) to afford 7-(8-chloroimidazo[1,5-a]pyrazin-3-yl)-3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine (0.34 g, yield 44%).

Workup

extractionThe resulting mixture was extracted with DCM
washthe combined organic layer was washed with water, brine
dry with materialdried over anhydrous Na2SO4
concentrationThe organic layer was concentrated in vacuo
customthe residue was purified by silica gel column chromatography (DCM/THF=100/20)

Sources & evidence

ORD record: ord-10baf883f2284b12ab50ea83528e820f
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09446130B2

Reaction notes

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