Trifluoroacetic acid → HCID 73295777, compound

HRID 523014Notes

Reaction equation

HRID 523014 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]([CH3:26])[N:24]=[CH:25][C:18]3=4)[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]([CH3:26])[N:24]=[CH:25][C:18]3=4)[N:15]=2)[NH:10][CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 90041275HCID 90041275, compound

Product 1

HCID 73295777HCID 73295777, compoundYield 59%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of N-tert-butyl-2-(1-methyl-6,7-dihydro-1H-pyrazolo[4,3-b]pyridin-4(5H)-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (77 mg, 159 μmol) in CH2Cl2 (4 mL) was added TFA (740 mg, 500 μL, 6.49 mmol). After 24 h the solvents were evaporated and the residue was re-dissolved in 5 mL of a mixture of (CH2Cl2/methanol/ammonium hydroxide; 60:10:1). After stirring at room temperature for 24 h, the mixture was concentrated in vacuo to a yellow solid, which was purified by chromatography (spherical silica 20-45 μm, 23 g, Versaflash Supelco, 0 to 5% 9:1 methanol:ammonium hydroxide in CH2Cl2, 30 min) to give a product that was dissolved in CH2Cl2 and precipitated by addition of cyclohexane. The yellow solid formed was separated by decantation of the mother liquor and then dried under high vacuum to give N-tert-butyl-2-(1-methyl-6,7-dihydro-1H-pyrazolo[4,3-b]pyridin-4(5H)-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (33 mg, 59%) as a yellow solid. 1H NMR (CHLOROFORM-d) δ: 8.95 (br. s., 1H), 8.24 (s, 1H), 8.02-8.14 (m, 2H), 7.85 (s, 1H), 3.88-3.99 (m, 2H), 3.83 (s, 3H), 2.81 (t, J=6.6 Hz, 2H), 2.08-2.24 (m, 2H), 1.55 (s, 9H). MS (EI/CI) m/z: 354.1 [M+H]+.

Workup

  1. customAfter 24 h the solvents were evaporated
  2. dissolutionthe residue was re-dissolved in 5 mL of a mixture of (CH2Cl2/methanol/ammonium hydroxide; 60:10:1)
  3. concentrationthe mixture was concentrated in vacuo to a yellow solid, which
  4. customwas purified by chromatography (spherical silica 20-45 μm, 23 g, Versaflash Supelco, 0 to 5% 9:1 methanol:ammonium hydroxide in CH2Cl2, 30 min)
  5. customto give a product that
  6. customprecipitated by addition of cyclohexane
  7. customThe yellow solid formed
  8. customwas separated by decantation of the mother liquor
  9. customdried under high vacuum

Sources & evidence

ORD record
ord-40ce5153bb0b4b5183d7177f7fea840a
Source dataset
uspto-grants-2016_05
Patent number
US09334278B2

Reaction notes

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