Trifluoroacetic acid → HCID 71280256, compound

HRID 246547Notes

Reaction equation

HRID 246547 reaction equation
[C:1]([NH:5][C:6]([C:8]1[C:12]2=[N:13][C:14]([C:17]3[N:18]=[CH:19][N:20]4[CH:25]=[C:24]([Cl:26])[CH:23]=[CH:22][C:21]=34)=[CH:15][N:16]=[C:11]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:12]2=[N:13][C:14]([C:17]3[N:18]=[CH:19][N:20]4[CH:25]=[C:24]([Cl:26])[CH:23]=[CH:22][C:21]=34)=[CH:15][N:16]=[C:11]2[NH:10][CH:9]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71279575HCID 71279575, compound

Product 1

HCID 71280256HCID 71280256, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of N-tert-butyl-2-(6-chloroimidazo[1,5-a]pyridin-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (50 mg, 100 μmol) in dichloromethane (1.5 mL) was added trifluoroacetic acid (228 mg, 154 μL, 2.00 mmol) and the mixture stirred at room temperature. After 16 h the reaction mixture was concentrated, then the residue was redissolved in dichloromethane (2 mL), methanol (1 mL) and ammonium hydroxide (0.22 mL) and stirred at room temperature. After 2 h the reaction was concentrated in vacuo. The residue was purified by chromatography (silica, 30-100% of a 0.5:10:89.5 ammonium hydroxide:methanol:dichloromethane solution in dichloromethane). The collected material was concentrated, triturated with methanol and filtered to give N-tert-butyl-2-(6-chloroimidazo[1,5-a]pyridin-1-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (12 mg, 29.6 μmol, 30%) as a yellow solid. MS (M+H)+=369.1; 1H NMR (DMSO-d6) δ: 12.69 (s, 1H), 9.08 (s, 1H), 8.79 (s, 1H), 8.53 (s, 1H), 8.34 (d, J=9.7 Hz, 1H), 8.30 (s, 1H), 7.84 (s, 1H), 7.05 (d, J=9.7 Hz, 1H); 1.52 (s, 9H).

Workup

  1. concentrationAfter 16 h the reaction mixture was concentrated
  2. dissolutionthe residue was redissolved in dichloromethane (2 mL)
  3. stirringmethanol (1 mL) and ammonium hydroxide (0.22 mL) and stirred at room temperature
  4. concentrationAfter 2 h the reaction was concentrated in vacuo
  5. customThe residue was purified by chromatography (silica, 30-100% of a 0.5:10:89.5 ammonium hydroxide:methanol:dichloromethane solution in dichloromethane)
  6. concentrationThe collected material was concentrated
  7. customtriturated with methanol
  8. filtrationfiltered

Sources & evidence

ORD record
ord-8375b3ccaec349b2817643fcdb55eac4
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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