Trifluoroacetic acid → HCID 71279740, compound

HRID 246519Notes

Reaction equation

HRID 246519 reaction equation
[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:17]3[C:25]4[C:20](=[CH:21][CH:22]=[C:23]([O:26][CH:27]([F:29])[F:28])[CH:24]=4)[N:19]([CH2:30][CH2:31][CH2:32][N:33]([CH3:37])[C:34](=[O:36])[CH3:35])[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]([C:17]3[C:25]4[C:20](=[CH:21][CH:22]=[C:23]([O:26][CH:27]([F:28])[F:29])[CH:24]=4)[N:19]([CH2:30][CH2:31][CH2:32][N:33]([C:34](=[O:36])[CH3:35])[CH3:37])[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 71280049HCID 71280049, compound

Product 1

HCID 71279740HCID 71279740, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of N-tert-butyl-2-(5-(difluoromethoxy)-1-(3-(N-methylacetamido)propyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (72 mg, 112 μmol) in dichloromethane (2 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 was added. After 1 h the mixture was concentrated in vacuo. Purification by chromatography (silica, 24 g Analogix column, 0 to 5% methanol containing 10% ammonium hydroxide in dichloromethane) gave 2-{1-[3-(acetyl-methyl-amino)-propyl]-5-difluoromethoxy-1H-indazol-3-yl}-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (32 mg, 56%). MS (M+H)+=514; 1H NMR (DMSO-d6) δ: 9.09 (s, 1H), 8.39 (s, 1H), 8.22 (br. s., 1H), 7.84-7.98 (m, 2H), 7.40 (d, J=9.8 Hz, 1H), 6.93-7.47 (m, 1H), 4.48-4.60 (m, 1H), 3.36-3.42 (m, 2H), 2.95 (s, 3H), 2.79 (s, 3H), 1.93 (d, J=7.5 Hz, 2H), 1.51 (s, 9H).

Workup

  1. concentrationAfter 15 h the mixture was concentrated in vacuo
  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 to 5% methanol containing 10% ammonium hydroxide in dichloromethane)

Sources & evidence

ORD record
ord-8968802bcc984ee3ad191d59f878e748
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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