Trifluoroacetic acid → N-isopropyl-2-(1-methyl-1,4,5,6-tetrahydrocyclopenta[c]pyrazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246373Notes

Reaction equation

HRID 246373 reaction equation
[CH:1]([NH:4][C:5]([C:7]1[C:15]2[C:10](=[N:11][CH:12]=[C:13]([C:16]3[C:17]4[CH2:24][CH2:23][CH2:22][C:18]=4[N:19]([CH3:21])[N:20]=3)[N:14]=2)[N:9](COCC[Si](C)(C)C)[CH:8]=1)=[O:6])([CH3:3])[CH3:2].C(O)(C(F)(F)F)=O>ClCCl>[CH:1]([NH:4][C:5]([C:7]1[C:15]2[C:10](=[N:11][CH:12]=[C:13]([C:16]3[C:17]4[CH2:24][CH2:23][CH2:22][C:18]=4[N:19]([CH3:21])[N:20]=3)[N:14]=2)[NH:9][CH:8]=1)=[O:6])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71280423N-isopropyl-2-(1-methyl-1,4,5,6-tetrahydrocyclopenta[c]pyrazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 71279966N-isopropyl-2-(1-methyl-1,4,5,6-tetrahydrocyclopenta[c]pyrazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideYield 92,666.703%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of N-isopropyl-2-(1-methyl-1,4,5,6-tetrahydrocyclopenta[c]pyrazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (68 mg, 150 μmol) in dichloromethane (5 mL) was added TFA (1.48 g, 1.00 mL, 13.0 mmol) and the reaction mixture stirred for 15 h then concentrated. The residue was re-dissolved in 5 mL of a solution of dichloromethane/MeOH/ammonium hydroxide (60:10:1) and stirred at 25° C. for 3 h, then evaporated and purified by chromatography (40 g column, 50 μm from Analogix, 0 to 5% MeOH containing 10% ammonium hydroxide in dichloromethane). The pure product was suspended in dichloromethane and cyclohexane added to promote solid formation, which was separated by decantation and dried under high vacuum to give N-isopropyl-2-(1-methyl-1,4,5,6-tetrahydrocyclopenta[c]pyrazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (45 mg, 139 mmol, 93%) as a white solid. MS (M+H)+=325; 1H NMR (DMSO-d6) δ: 12.68 (br. s., 1H), 8.87 (s, 1H), 8.31 (s, 1H), 8.00 (d, J=7.9 Hz, 1H), 4.02-4.46 (m, 1H), 3.79 (s, 3H), 2.92 (t, J=6.4 Hz, 2H), 2.73 (t, J=6.4 Hz, 2H), 2.60 (t, J=6.4 Hz, 2H), 1.24 (d, J=6.4 Hz, 6H).

Workup

  1. concentrationthen concentrated
  2. dissolutionThe residue was re-dissolved in 5 mL of a solution of dichloromethane/MeOH/ammonium hydroxide (60:10:1)
  3. stirringstirred at 25° C. for 3 h
  4. customevaporated
  5. custompurified by chromatography (40 g column, 50 μm from Analogix, 0 to 5% MeOH containing 10% ammonium hydroxide in dichloromethane)
  6. additioncyclohexane added
  7. customwas separated by decantation
  8. customdried under high vacuum

Sources & evidence

ORD record
ord-d8a160e0e22041a4be3a214bb50b5ccf
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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