Trifluoroacetic acid → HCID 71280612, compound

HRID 246514Notes

Reaction equation

HRID 246514 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]4[CH2:37][CH2:36][C:35]([F:39])([F:38])[CH2:34]4)[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:29])[F:28])[CH:24]=4)[N:19]([CH2:30][CH2:31][CH2:32][N:33]4[CH2:37][CH2:36][C:35]([F:38])([F:39])[CH2:34]4)[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 71279783HCID 71279783, compound

Product 1

HCID 71280612HCID 71280612, compoundYield 43.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of N-tert-butyl-2-(5-(difluoromethoxy)-1-(3-(3,3-difluoropyrrolidin-1-yl)propyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (91.4 mg, 135 μmol) in dichloromethane (2 mL) was added trifluoroacetic acid (1 mL). After 15 h the mixture was concentrated in vacuo. 25 mL of a Jan. 10, 1960 mixture of ammonium hydroxide/methanol/dichloromethane was added, and the reaction mixture stirred for 1 h then concentrated in vacuo. Purification by chromatography (silica, 24 g Analogix column, 0-4% methanol containing 10% ammonium hydroxide in dichloromethane) gave 2-{5-Difluoromethoxy-1-[3-(3,3-difluoro-pyrrolidin-1-yl)-propyl]-1H-indazol-3-yl}-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (32 mg, 43%). MS (M+H)+=548; 1H NMR (DMSO-d6) δ: 9.09 (s, 1H), 8.38 (s, 1H), 8.21 (d, J=2.3 Hz, 2H), 7.88 (s, 2H), 7.86 (s, 1H), 7.36-7.43 (m, 1H), 6.92-7.49 (m, 1H), 4.59 (t, J=6.8 Hz, 2H), 2.84 (t, J=13.6 Hz, 2H), 2.64 (t, J=7.0 Hz, 2H), 2.43 (t, J=6.7 Hz, 1H), 2.15-2.29 (m, 2H), 2.08 (t, J=7.0 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. concentrationthen concentrated in vacuo
  5. customPurification by chromatography (silica, 24 g Analogix column, 0-4% methanol containing 10% ammonium hydroxide in dichloromethane)

Sources & evidence

ORD record
ord-45f6c5187cb242098dc9d881e0f6c41b
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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