Trifluoroacetic acid → HCID 71280356, compound

HRID 246512Notes

Reaction equation

HRID 246512 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][CH:31]4[O:36][CH2:35][CH2:34][N:33]([CH3:37])[CH2:32]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][CH:31]4[O:36][CH2:35][CH2:34][N:33]([CH3:37])[CH2:32]4)[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 71280516N-tert-butyl-2-(5-(difluoromethoxy)-1-((4-methylmorpholin-2-yl)methyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 71280356HCID 71280356, compoundYield 43.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of N-tert-butyl-2-(5-(difluoromethoxy)-1-((4-methylmorpholin-2-yl)methyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (63 mg, 97.9 μmol) in dichloromethane (2 mL) was added trifluoroacetic acid (1 mL). After stirring at room temperature for 15 h the mixture was concentrated in vacuo then 25 mL Jan. 10, 1960 mixture of ammonium hydroxide/methanol/dichloromethane was added. After 1 h the mixture was concentrated and purified by chromatography (silica, 24 g Analogix column, 0-4% methanol containing 10% ammonium hydroxide in dichloromethane) to give 2-[5-difluoromethoxy-1-(4-methyl-morpholin-2-ylmethyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (22 mg, 43%). MS (M+H)+=514; 1H NMR (DMSO-d6) δ: 9.07 (s, 1H), 8.39 (s, 1H), 8.19 (d, J=2.3 Hz, 1H), 7.89 (s, 1H), 7.86 (s, 1H), 7.39 (dd, J=9.0, 2.3 Hz, 1H), 7.20 (s, 1H), 4.58-4.68 (m, 2H), 3.74 (d, J=11.9 Hz, 1H), 3.37-3.48 (m, 1H), 2.79 (d, J=11.3 Hz, 1H), 2.57 (br. s., 3H), 2.18 (s, 3H), 1.84-2.01 (m, 1H), 1.51 (s, 9H).

Workup

  1. concentrationwas concentrated in vacuo
  2. addition10, 1960 mixture of ammonium hydroxide/methanol/dichloromethane
  3. additionwas added
  4. concentrationAfter 1 h the mixture was concentrated
  5. custompurified by chromatography (silica, 24 g Analogix column, 0-4% methanol containing 10% ammonium hydroxide in dichloromethane)

Sources & evidence

ORD record
ord-e3a2fa7ea83a4e9491d1eb48457f7d76
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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