Trifluoroacetic acid → N-isopropyl-2-(1,5,5-trimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246353Notes

Reaction equation

HRID 246353 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:24]4[CH2:23][C:22]([CH3:26])([CH3:25])[CH2:21][CH2:20][C:19]=4[N:18]([CH3:27])[N:17]=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:24]4[CH2:23][C:22]([CH3:25])([CH3:26])[CH2:21][CH2:20][C:19]=4[N:18]([CH3:27])[N:17]=3)[N:14]=2)[NH:9][CH:8]=1)=[O:6])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71280397N-isopropyl-2-(1,5,5-trimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 71280420N-isopropyl-2-(1,5,5-trimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideYield 72%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of N-isopropyl-2-(1,5,5-trimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (113 mg, 227 mmol) in dichloromethane (3 mL) was added TFA (1.48 g, 1 mL, 13.0 mmol). The reaction mixture was stirred at 25° C. 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 to a yellow solid. The solid was dissolved in dichloromethane (containing a few drops of MeOH) and purified by chromatography (40 g, 50 μm particle size, Analogix, 0 to 5% MeOH containing 10% ammonium hydroxide in dichloromethane, 15 min). The pure product was re-dissolved in MeOH and allowed to stand for solid formation. The solid was separated by decanting the mother liquors and then dried to give N-isopropyl-2-(1,5,5-trimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (60 mg, 164 μmol, 72%) as a white needles. MS (M+H)+=367; 1H NMR (300 MHz, DMSO-d6) δ ppm 12.47-12.74 (m, 1H), 8.91 (s, 1H), 8.31 (s, 1H), 7.92 (d, J=8.31 Hz, 1H), 4.07-4.48 (m, 1H), 3.78 (s, 3H), 2.72 (s, 2H), 2.64 (t, J=6.42 Hz, 2H), 1.60 (t, J=6.42 Hz, 2H), 1.26 (d, J=6.42 Hz, 6H), 1.01 (s, 6H).

Workup

  1. concentrationthen concentrated
  2. dissolutionThe residue was re-dissolved in 5 mL of a solution of dichloromethane/MeOH/ammonium hydroxide
  3. stirring60:10:1 and stirred at 25° C. for 3 h
  4. customevaporated to a yellow solid
  5. dissolutionThe solid was dissolved in dichloromethane (containing a few drops of MeOH)
  6. custompurified by chromatography (40 g, 50 μm particle size, Analogix, 0 to 5% MeOH containing 10% ammonium hydroxide in dichloromethane, 15 min)
  7. dissolutionThe pure product was re-dissolved in MeOH
  8. customThe solid was separated
  9. customby decanting the mother liquors
  10. customdried

Sources & evidence

ORD record
ord-a6437fa86ba249c091d2cc48bdf013d6
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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