Trifluoroacetic acid → HCID 71280035, compound

HRID 246532Notes

Reaction equation

HRID 246532 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][CH:31]4[CH2:33][CH2:32]4)[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.ClCCl.CO>[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][CH:31]4[CH2:32][CH2:33]4)[N:18]=3)[N:15]=2)[NH:10][CH:9]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71279907N-tert-butyl-2-(1-(cyclopropylmethyl)-5-(difluoromethoxy)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 71280035HCID 71280035, compoundYield 66.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
25 °C

Procedure

To a stirred solution of N-tert-butyl-2-(1-(cyclopropylmethyl)-5-(difluoromethoxy)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (140 mg, 239 μmol) in dichloromethane (10 mL) under Ar, trifluoroacetic acid (744 mg, 0.50 mL, 6.53 mmol) was added at 25° C. After 18 h, the reaction was concentrated in vacuo to give a light brown residue. The residue was dissolved in a mixture of dichloromethane/methanol/NH3OH (3:2:0.25, 10.5 mL) and stirred at 25° C. After 2.5 h, the reaction was concentrated to give a yellow solid and dried in vacuo (200 mTorr, 25° C.). The solid was dissolved in ethanol (4.5 mL, 200 proof) and cooled to 4° C. After 18 h, the precipitated solid was isolated by filtration and dried in vacuo (200 mTorr, 40° C.) to give N-tert-butyl-2-(1-(cyclopropylmethyl)-5-(difluoromethoxy)-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (72.8 mg, 160 μmol, 66.9%) as a yellow solid. MS (M)'=455; 1H NMR (DMSO-d6) δ: 9.09 (s, 1H), 8.39 (s, 1H), 8.21 (d, J=2.3 Hz, 1H), 7.93 (d, J=9.0 Hz, 1H), 7.88 (s, 1H), 7.40 (dd, J=2.3, 9.0 Hz, 1H), 7.20 (t, J=74.3 Hz, 1H), 5.86 (m, 1H), 5.08 (dd, J=1.5, 17.3 Hz, 2H), 4.63 (t, J=7.0 Hz, 2H), 2.71 (m, 2H), 1.51 (s, 9H).

Workup

  1. concentrationthe reaction was concentrated in vacuo
  2. customto give a light brown residue
  3. waitAfter 2.5 h
  4. concentrationthe reaction was concentrated
  5. customto give a yellow solid
  6. customdried in vacuo (200 mTorr, 25° C.)
  7. dissolutionThe solid was dissolved in ethanol (4.5 mL, 200 proof)
  8. temperaturecooled to 4° C
  9. waitAfter 18 h
  10. customthe precipitated solid was isolated by filtration
  11. customdried in vacuo (200 mTorr, 40° C.)

Sources & evidence

ORD record
ord-e99d9892f7014ad8a409a8cf62df53e4
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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