Trifluoroacetic acid → HCID 71280309, compound

HRID 246539Notes

Reaction equation

HRID 246539 reaction equation
[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:17]3[C:25]4[C:20](=[CH:21][CH:22]=[C:23]([O:26][CH:27]([F:29])[F:28])[CH:24]=4)[N:19]([CH2:30][C:31]([NH:33][CH3:34])=[O:32])[N:18]=3)[N:15]=2)[N:10](COCC[Si](C)(C)C)[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].FC(F)(F)C(O)=O>ClCCl>[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:17]3[C:25]4[C:20](=[CH:21][CH:22]=[C:23]([O:26][CH:27]([F:28])[F:29])[CH:24]=4)[N:19]([CH2:30][C:31]([NH:33][CH3:34])=[O:32])[N:18]=3)[N:15]=2)[NH:10][CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71279632HCID 71279632, compound

Product 1

HCID 71280309HCID 71280309, compoundYield 80%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of N-tert-butyl-2-(5-(difluoromethoxy)-1-(2-(methylamino)-2-oxoethyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (69.0 mg, 115 μmol) in dichloromethane (3.00 mL) under Ar, trifluoroacetic acid (372 mg, 0.25 mL, 3.26 mmol) was added at 25° C. After 18 h, the solvent was removed and the residue was dissolved in a mix of dichloromethane/methanol/NH3OH (3:2:0.25, 5.25 mL) and stirred. After 2.5 h, the reaction was concentrated and dried in vacuo (200 mTorr, 25° C.). The solid residue was triturated with water (50 mL) and isolated by filtration. The solid was washed with water and hexanes and dried in vacuo (200 mTorr, 40° C.) to give N-tert-butyl-2-(5-(difluoromethoxy)-1-(2-(methylamino)-2-oxoethyl)-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (45.6 mg, 91.9 μmol, 80%) as a light brown solid. MS (M)'=472; 1H NMR (DMSO-d6) δ: 12.83 (br. s, 1H), 9.04 (s, 1H), 8.39 (d, J=2.8 Hz, 1H), 8.21 (m, 2H), 7.89 (s, 1H), 7.81 (d, J=9.0 Hz, 1H), 7.40 (dd, J=2.0, 9.0 Hz, 1H), 7.20 (t, J=74.3 Hz, 1H), 5.24 (s 2H), 2.65 (m, 3H), 1.51 (s, 9H).

Workup

  1. customthe solvent was removed
  2. dissolutionthe residue was dissolved in
  3. additiona mix of dichloromethane/methanol/NH3OH (3:2:0.25, 5.25 mL)
  4. waitAfter 2.5 h
  5. concentrationthe reaction was concentrated
  6. customdried in vacuo (200 mTorr, 25° C.)
  7. customThe solid residue was triturated with water (50 mL)
  8. customisolated by filtration
  9. washThe solid was washed with water and hexanes
  10. customdried in vacuo (200 mTorr, 40° C.)

Sources & evidence

ORD record
ord-5511ebfae66b4df29c2d349c95b14401
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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