Trifluoroacetic acid → HCID 71279812, compound

HRID 246489Notes

Reaction equation

HRID 246489 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]([CH3:26])[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]([CH3:26])[CH:24]=4)[CH:19]=[N:18]3)[N:15]=2)[NH:10][CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71279530HCID 71279530, compound

Product 1

HCID 71279812HCID 71279812, compoundYield 48.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of N-tert-butyl-2-(6-methyl-1H-indazol-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (100 mg, 209 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, 0-4% methanol containing 10% ammonium hydroxide in dichloromethane, 15 min gradient) gave 2-(6-methyl-indazol-1-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (35 mg, 48%). MS (M+H)+=349; 1H NMR (DMSO-d6) δ: 8.95 (s, 1H), 8.45 (d, J=0.8 Hz, 1H), 8.41 (s, 1H), 8.29 (s, 1H), 7.84 (d, J=8.3 Hz, 1H), 7.71 (s, 1H), 7.21 (dd, J=8.3, 0.8 Hz, 1H), 2.53 (s, 3H), 1.49 (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, 0-4% methanol containing 10% ammonium hydroxide in dichloromethane, 15 min gradient)

Sources & evidence

ORD record
ord-045ee8eddb7d493bb8651f0c8e6717d4
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

Loading…