Trifluoroacetic acid → 2-(6-chloro-indazol-1-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide

HRID 246485Notes

Reaction equation

HRID 246485 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[C:25]4[C:20](=[CH:21][CH:22]=[C:23]([Cl:26])[CH:24]=4)[CH:19]=[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]([N:17]3[C:25]4[C:20](=[CH:21][CH:22]=[C:23]([Cl:26])[CH:24]=4)[CH:19]=[N:18]3)[N:15]=2)[NH:10][CH:9]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71280597N-tert-butyl-2-(6-chloro-1H-indazol-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 712803962-(6-chloro-indazol-1-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamideYield 57%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of N-tert-butyl-2-(6-chloro-1H-indazol-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (120 mg, 240 μmol) in dichloromethane (3 mL) was added trifluoroacetic acid (1 mL). After 15 h, the mixture was concentrated in vacuo then 25 mL of a Jan. 10, 1960 mixture of ammonium hydroxide/methanol/dichloromethane added. After 1 h the mixture was concentrated in vacuo. Purification by chromatography (silica, 24 g Analogix column, 0 to 5% of a solution of methanol containing 10% ammonium hydroxide in dichloromethane) gave 2-(6-chloro-indazol-1-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (50.4 mg, 57%). MS: (M+H)+=369; 1H NMR (DMSO-d6) δ: 8.97 (s, 1H), 8.57 (s, 2H), 8.43 (s, 1H), 8.00 (dd, J=8.5, 0.5 Hz, 1H), 7.61 (s, 1H), 7.41 (dd, J=8.5, 1.8 Hz, 1H), 1.50 (s, 9H).

Workup

  1. concentrationthe mixture was concentrated in vacuo
  2. addition10, 1960 mixture of ammonium hydroxide/methanol/dichloromethane
  3. additionadded
  4. concentrationAfter 1 h the mixture was concentrated in vacuo
  5. customPurification by chromatography (silica, 24 g Analogix column, 0 to 5% of a solution of methanol containing 10% ammonium hydroxide in dichloromethane)

Sources & evidence

ORD record
ord-888a02a0392d48cdbddbaaaa3eee094e
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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