Trifluoroacetic acid → HCID 50991859, compound
Reaction equation
[CH:1]1([N:4]([CH:43]2[CH2:45][CH2:44]2)[C:5]([C:7]2[N:40]([CH2:41][CH3:42])[C:10]3=[N:11][C:12]([NH:19]/[C:20](/[NH:29][N:30]([CH2:38][CH3:39])C(OC(C)(C)C)=O)=[CH:21]/[C:22](=O)[CH:23]([O:26]C)OC)=[C:13]4[N:17]=[CH:16][N:15]([CH3:18])[C:14]4=[C:9]3[CH:8]=2)=[O:6])[CH2:3][CH2:2]1.C(O)(C(F)(F)F)=O>>[CH:43]1([N:4]([CH:1]2[CH2:2][CH2:3]2)[C:5]([C:7]2[N:40]([CH2:41][CH3:42])[C:10]3=[N:11][C:12]([NH:19][C:20]4[CH:21]=[C:22]([CH:23]=[O:26])[N:30]([CH2:38][CH3:39])[N:29]=4)=[C:13]4[N:17]=[CH:16][N:15]([CH3:18])[C:14]4=[C:9]3[CH:8]=2)=[O:6])[CH2:44][CH2:45]1Participants
3
Conditions
- Temperature
- 60 °C
Procedure
A mixture of (Z)-tert-butyl 2-(1-(7-(dicyclopropylcarbamoyl)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-ylamino)-4,4-dimethoxy-3-oxobut-1-enyl)-1-ethylhydrazinecarboxylate (187 mg, 0.299 mmol) and TFA (25% in dichloroethane, 1.0 mL, 2.99 mmol) was heated at 60° C. for 0.5 h and LC/MS showed completion of reaction. Solvent was evaporated and the residue was partitioned between saturated sodium bicarbonate and dichloromethane. The layers were separated and aqueous layer was extracted with dichloromethane two more times. The combined organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel using an automated ISCO system (24 g column, eluting with 1-5% methanol/dichloromethane). N,N-dicyclopropyl-6-ethyl-4-(1-ethyl-5-formyl-1H-pyrazol-3-ylamino)-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (80 mg, 0.174 mmol, 58.0% yield) was obtained as a yellow solid.