Trifluoroacetic acid → HCID 73295946, compound

HRID 523011Notes

Reaction equation

HRID 523011 reaction equation
[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([N:17]3[CH2:22][CH2:21][CH2:20][C:19]4=[N:23][N:24]([CH3:26])[CH:25]=[C:18]34)[N:15]=2)[N:10](COCC[Si](C)(C)C)[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([N:17]3[CH2:22][CH2:21][CH2:20][C:19]4=[N:23][N:24]([CH3:26])[CH:25]=[C:18]34)[N:15]=2)[NH:10][CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 90040990HCID 90040990, compound

Product 1

HCID 73295946HCID 73295946, compoundYield 36.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of N-tert-butyl-2-(2-methyl-6,7-dihydro-2H-pyrazolo[4,3-b]pyridin-4(5H)-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (87 mg, 180 μmol) in CH2Cl2 (4 mL) was added TFA (740 mg, 500 μL, 6.49 mmol). After 24 h, the mixture was concentrated in vacuo and the residue was re-dissolved in 5 mL of a mixture of (CH2Cl2/methanol/ammonium hydroxide; 60:10:1) and the mixture stirred at room temperature for 24 h, then evaporated to a yellow solid, which was purified by chromatography (spherical silica 20-45 m, 23 g, Versaflash Supelco, 0 to 5% 9:1 methanol:ammonium hydroxide in CH2Cl2, 30 min) to give a residue that was dissolved in CH2Cl2 then precipitated with cyclohexane. The yellow solid was obtained by decanting the mother liquor and dried under high vacuum to give N-tert-butyl-2-(2-methyl-6,7-dihydro-2H-pyrazolo[4,3-b]pyridin-4(5H)-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (23 mg, 36%). 1H NMR (CHLOROFORM-d) δ: 9.46 (br. s., 1H), 8.08-8.21 (m, 2H), 7.97 (br. s., 1H), 7.82 (s, 1H), 3.88 (m, 5H), 2.89 (t, J=6.2 Hz, 2H), 2.14-2.28 (m, 2H), 1.56 (s, 9H). MS (EI/CI) m/z: 354.1 [M+H]+.

Workup

  1. concentrationthe mixture was concentrated in vacuo
  2. dissolutionthe residue was re-dissolved in 5 mL of a mixture of (CH2Cl2/methanol/ammonium hydroxide; 60:10:1)
  3. customevaporated to a yellow solid, which
  4. customwas purified by chromatography (spherical silica 20-45 m, 23 g, Versaflash Supelco, 0 to 5% 9:1 methanol:ammonium hydroxide in CH2Cl2, 30 min)
  5. customto give a residue that
  6. customthen precipitated with cyclohexane
  7. customThe yellow solid was obtained
  8. customby decanting the mother liquor
  9. customdried under high vacuum

Sources & evidence

ORD record
ord-7f2384ab32174ad59fe6bc5d58c87fc7
Source dataset
uspto-grants-2016_05
Patent number
US09334278B2

Reaction notes

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