Trifluoroacetic acid → HCID 71288635, compound

HRID 246022Notes

Reaction equation

HRID 246022 reaction equation
[C:1]([C:3]([CH3:38])([CH3:37])[C@@H:4]([NH:6][C:7]([C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:18]3[C:26]4[C:21](=[CH:22][C:23]([Cl:27])=[CH:24][CH:25]=4)[N:20]([CH3:28])[N:19]=3)[N:16]=2)[N:11](COCC[Si](C)(C)C)[CH:10]=1)=[O:8])[CH3:5])#[N:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[C:1]([C:3]([CH3:37])([CH3:38])[C@@H:4]([NH:6][C:7]([C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:18]3[C:26]4[C:21](=[CH:22][C:23]([Cl:27])=[CH:24][CH:25]=4)[N:20]([CH3:28])[N:19]=3)[N:16]=2)[NH:11][CH:10]=1)=[O:8])[CH3:5])#[N:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71286175HCID 71286175, compound

Product 1

HCID 71288635HCID 71288635, compoundYield 84%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-cyano-1,2,2-trimethyl-ethyl)-amide (120 mg, 0.22 mmol) in CH2Cl2 (2 mL) was added TFA (0.75 mL). The reaction mixture was stirred at room temperature for 2 h then concentrated. The residue was redissolved in 10:90:0.5 MeOH/CH2Cl2/NH4OH (3 mL) and stirred at room temperature for 3 h then concentrated. The residue was taken up in 10% MeOH/CH2Cl2 and water was added. The resultant precipitate was collected via filtration then triturated with EtOAc to afford 77 mg (84%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-cyano-1,2,2-trimethyl-ethyl)-amide as a light yellow powder. MS: (M+H)+=422; mp=322-328° C.; 1H NMR (DMSO-d6, 400 MHz): δ (ppm) 12.78 (s, 1H), 8.99 (s, 1H), 8.38 (s, 1H), 8.34 (d, J=9.1 Hz, 1H), 8.01 (d, J=9.6 Hz, 1H), 7.86 (d, J=1.5 Hz, 1H), 7.19 (dd, J=8.6, 1.5 Hz, 1H), 4.20-4.34 (m, 1H), 4.04 (s, 3H), 1.31 (d, J=6.6 Hz, 3H), 1.28 (s, 3H), 1.25 (s, 3H).

Workup

  1. concentrationthen concentrated
  2. dissolutionThe residue was redissolved in 10:90:0.5 MeOH/CH2Cl2/NH4OH (3 mL)
  3. stirringstirred at room temperature for 3 h
  4. concentrationthen concentrated
  5. additionwater was added
  6. filtrationThe resultant precipitate was collected via filtration
  7. customthen triturated with EtOAc

Sources & evidence

ORD record
ord-4e5ae8358f174261b5c1c2f345b116eb
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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