Dimethylformamide → 8-chloro-3-(1-methyl-4,5,6,7-tetrahydro-1H-indazol-4-yl)imidazo[1,5-a]pyrazine

HRID 62445Notes

Reaction equation

[Cl:1][C:2]1[C:3]([CH2:8][NH:9][C:10]([CH:12]2[CH2:20][CH2:19][CH2:18][C:17]3[N:16]([CH3:21])[N:15]=[CH:14][C:13]2=3)=O)=[N:4][CH:5]=[CH:6][N:7]=1.O=P(Cl)(Cl)Cl.CN(C=O)C>CC#N>[Cl:1][C:2]1[C:3]2[N:4]([C:10]([CH:12]3[CH2:20][CH2:19][CH2:18][C:17]4[N:16]([CH3:21])[N:15]=[CH:14][C:13]3=4)=[N:9][CH:8]=2)[CH:5]=[CH:6][N:7]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of N-((3-chloropyrazin-2-yl)methyl)-1-methyl-4,5,6,7-tetrahydro-1H-indazole-4-carboxamide (1.5 g, 4.9 mmol) in MeCN (50 mL) was added POCl3 (1.2 g, 7.9 mmol) dropwise and DMF (0.1 mL). The mixture was stirred at 60° C. for 4 hours. After cooling, the mixture was poured into ice-water and extracted with EA three times. The EA layer was washed with brine and dried over Na2SO4. The solvent was removed and the residue was purified by column chromatography on silica gel (DCM/methanol=40/1 v/v %) to afford 8-chloro-3-(1-methyl-4,5,6,7-tetrahydro-1H-indazol-4-yl)imidazo[1,5-a]pyrazine (1.0 g, 70.4%). MS-ESI (m/z): 288 (M+1)+ (Acq Method: 10-80AB_2 min_220 &254.1 cm; Rt: 0.85 min)

Workup

temperatureAfter cooling
extractionextracted with EA three times
washThe EA layer was washed with brine
dry with materialdried over Na2SO4
customThe solvent was removed
customthe residue was purified by column chromatography on silica gel (DCM/methanol=40/1 v/v %)

Sources & evidence

ORD record: ord-0627891ac40645dfa111ae4f48a7c8dd
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09446130B2

Reaction notes

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