Trifluoroacetic acid → HCID 67347553, compound

HRID 246477Notes

Reaction equation

HRID 246477 reaction equation
[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14](N3C4C(=CC(OC(F)F)=CC=4)C=N3)[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]=[CH:14][N:15]=2)[NH:10][CH:9]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71280330HCID 71280330, compound

Product 1

HCID 67347553HCID 67347553, compoundYield 103.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of N-tert-butyl-2-(5-(difluoromethoxy)-1H-indazol-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (130 mg, 245 μmol) in dichloromethane (1 mL) was added trifluoroacetic acid (1 mL). After 15 h, then mixture was concentrated in vacuo and 25 mL of a Jan. 10, 1960 mixture of ammonium hydroxide/methanol/dichloromethane was added. After 1 h the mixture was concentrated in vacuo. Purification by chromatography (silica, 24 g Analogix column, 0-5% of a solution of methanol containing 10% ammonium hydroxide in dichloromethane) gave 245-difluoromethoxy-indazol-1-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (55.3 mg, 56%). MS: (M+H)+=401; 1H NMR (DMSO-d6) δ: 9.09 (s, 1H), 8.57 (s, 1H), 8.51 (s, 1H), 7.78 (d, J=2.3 Hz, 2H), 7.43 (dd, J=9.0, 2.5 Hz, 2H), 7.31 (s, 1H), 1.51 (s, 9H).

Workup

  1. concentrationmixture was concentrated in vacuo and 25 mL of a Jan
  2. addition10, 1960 mixture of ammonium hydroxide/methanol/dichloromethane
  3. additionwas added
  4. concentrationAfter 1 h the mixture was concentrated in vacuo
  5. customPurification by chromatography (silica, 24 g Analogix column, 0-5% of a solution of methanol containing 10% ammonium hydroxide in dichloromethane)

Sources & evidence

ORD record
ord-54c267e918394aeca265c75594436fb9
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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