Trifluoroacetic acid → 2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246380Notes

Reaction equation

HRID 246380 reaction equation
[F:1][CH:2]([F:37])[O:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH3:13])[N:8]=[C:7]2[C:14]1[N:15]=[C:16]2[C:22]([C:23]([NH:25][CH:26]([CH3:28])[CH3:27])=[O:24])=[CH:21][N:20](COCC[Si](C)(C)C)[C:17]2=[N:18][CH:19]=1.C(O)(C(F)(F)F)=O>ClCCl>[F:37][CH:2]([F:1])[O:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH3:13])[N:8]=[C:7]2[C:14]1[N:15]=[C:16]2[C:22]([C:23]([NH:25][CH:26]([CH3:27])[CH3:28])=[O:24])=[CH:21][NH:20][C:17]2=[N:18][CH:19]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 712794372-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-N-isopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 712799912-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideYield 94%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

To a pale yellow solution of 2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-N-isopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (32.5 mg, 61.2 μmol) in dichloromethane (1.44 mL) was added TFA (426 mg, 288 μL, 3.73 mmol) and stirred at 25° C. for 15 h. The mixture was concentrated then 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 an off-white solid which was purified by chromatography (spherical silica 20-45 μm, 23 g, Versaflash Supelco, 0 to 5% MeOH containing 10% ammonium hydroxide in dichloromethane). The pure product was dissolved in dichloromethane/MeOH and dichloromethane evaporated to allow solid formation, then the solid was collected by filtration and dried to give 2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (23 mg, 57.4 μmol, 94%) as a light yellow solid. MS (M+H)+=401; 1H NMR (DMSO-d6) δ: 12.83 (br. s., 1H), 9.10 (s, 1H), 8.41 (s, 1H), 8.20 (d, J=2.3 Hz, 1H), 7.96 (d, J=7.9 Hz, 1H), 7.86 (d, J=9.4 Hz, 1H), 7.42 (dd, J=9.1, 1.9 Hz, 1H), 7.21 (t, J=74.4 Hz, 1H), 4.12-4.33 (m, 4H), 2.49 (s, 9H), 1.30 (d, J=6.4 Hz, 6H).

Workup

  1. concentrationThe mixture was concentrated
  2. dissolutionthen 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 to an off-white solid which
  5. customwas purified by chromatography (spherical silica 20-45 μm, 23 g, Versaflash Supelco, 0 to 5% MeOH containing 10% ammonium hydroxide in dichloromethane)
  6. dissolutionThe pure product was dissolved in dichloromethane/MeOH
  7. customdichloromethane evaporated
  8. filtrationthe solid was collected by filtration
  9. customdried

Sources & evidence

ORD record
ord-2ed119bb97b84ff79d7401dd50c343c4
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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