Trifluoroacetic acid → 2-(6-fluoro-1-oxetan-3-yl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide

HRID 246077Notes

Reaction equation

HRID 246077 reaction equation
[CH:1]([NH:4][C:5]([C:7]1[C:15]2[C:10](=[N:11][CH:12]=[C:13]([C:16]3[C:24]4[C:19](=[CH:20][C:21]([F:25])=[CH:22][CH:23]=4)[N:18]([CH:26]4[CH2:29][O:28][CH2:27]4)[N:17]=3)[N:14]=2)[N:9](COCC[Si](C)(C)C)[CH:8]=1)=[O:6])([CH3:3])[CH3:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH:1]([NH:4][C:5]([C:7]1[C:15]2[C:10](=[N:11][CH:12]=[C:13]([C:16]3[C:24]4[C:19](=[CH:20][C:21]([F:25])=[CH:22][CH:23]=4)[N:18]([CH:26]4[CH2:27][O:28][CH2:29]4)[N:17]=3)[N:14]=2)[NH:9][CH:8]=1)=[O:6])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 712796982-(6-fluoro-1-oxetan-3-yl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide

Product 1

HCID 712797562-(6-fluoro-1-oxetan-3-yl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamideYield 42.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(6-fluoro-1-oxetan-3-yl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide (98 mg, 0.18 mmol) in CH2Cl2 (1.5 mL) was added TFA (0.5 mL). The reaction mixture was stirred at room temperature for 3 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 portioned between water and 10% MeOH/CH2Cl2. The aqueous layer was extracted with 10% MeOH/CH2Cl2 (3×). The combined organics were concentrated and the residue was purified by silica gel chromatography with 0% to 5% MeOH/CH2Cl2 (0.5% NH4OH) to afford 30 mg (41%) of 2-(6-fluoro-1-oxetan-3-yl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide as a white solid. MS (M+Na)+=417; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 12.87 (br. s., 1H), 9.20 (s, 1H), 8.45-8.51 (m, 1H), 8.44 (s, 1H), 8.04 (d, J=7.6 Hz, 1H), 7.73 (dd, J=9.8, 1.9 Hz, 1H), 7.22 (td, J=9.1, 1.9 Hz, 1H), 6.13 (quin, J=7.0 Hz, 1H), 5.11-5.20 (m, 2H), 4.99-5.10 (m, 2H), 4.21 (dq, J=13.5, 6.4 Hz, 1H), 1.30 (d, J=6.4 Hz, 6H).

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. extractionThe aqueous layer was extracted with 10% MeOH/CH2Cl2 (3×)
  6. concentrationThe combined organics were concentrated
  7. customthe residue was purified by silica gel chromatography with 0% to 5% MeOH/CH2Cl2 (0.5% NH4OH)

Sources & evidence

ORD record
ord-afac779293264f27a09317d376359c42
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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