Trifluoroacetic acid → HCID 50991859, compound

HRID 220401Notes

Reaction equation

HRID 220401 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]1

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 58180642(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

Product 1

HCID 50991859HCID 50991859, compoundYield 58.2%

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.

Workup

  1. customcompletion of reaction
  2. customSolvent was evaporated
  3. customthe residue was partitioned between saturated sodium bicarbonate and dichloromethane
  4. customThe layers were separated
  5. extractionaqueous layer was extracted with dichloromethane two more times
  6. dry with materialThe combined organic layer was dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by flash chromatography on silica gel using
  10. washan automated ISCO system (24 g column, eluting with 1-5% methanol/dichloromethane)

Sources & evidence

ORD record
ord-8b2107488f494cc791289046b02eb5be
Source dataset
uspto-grants-2012_06
Patent number
US08202881B2

Reaction notes

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