Trifluoroacetic acid → 3-(7-(tert-butylcarbamoyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)-1-methyl-4,5,6,7-tetrahydro-1H-indazole 2-oxide

HRID 246412Notes

Reaction equation

HRID 246412 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[CH2:24][CH2:23][CH2:22][CH2:21][C:20]=4[N:19]([CH3:26])[N+:18]=3[O-:27])[N:15]=2)[N:10](COCC[Si](C)(C)C)[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(O)(C(F)(F)F)=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[CH2:24][CH2:23][CH2:22][CH2:21][C:20]=4[N:19]([CH3:26])[N+:18]=3[O-:27])[N:15]=2)[NH:10][CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 712800513-(7-(tert-butylcarbamoyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)-1-methyl-4,5,6,7-tetrahydro-1H-indazole 2-oxide

Product 1

HCID 1363594913-(7-(tert-butylcarbamoyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)-1-methyl-4,5,6,7-tetrahydro-1H-indazole 2-oxideYield 88,167.102%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

To a pale yellow solution of 3-(7-(tert-butylcarbamoyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)-1-methyl-4,5,6,7-tetrahydro-1H-indazole 2-oxide (43 mg, 86.2 μmol) in dichloromethane (2.00 mL) was added TFA (1.48 g, 1.00 mL, 13.0 mmol51), the reaction mixture turned dark red and was stirred at 25° C. overnight then concentrated. The residue was re-dissolved in 5 mL of a solution of (dichloromethane/MeOH/ammonium hydroxide; 60:10:1) and stirred at 25° C. for 3 h, then evaporated to a light yellow solid, dissolved in dichloromethane (added few drops MeOH and heating) and purified by chromatography (spherical silica 20-45 μm, 23 g, Versaflash Supelco) eluting with 0 to 10% over 15 min (MeOH containing 10% ammonium hydroxide)/dichloromethane. Pure white solid product was sonicated with hexanes. The solid was separated by decantation and dried under high vacuum to give 3-(7-(tert-butylcarbamoyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)-1-methyl-4,5,6,7-tetrahydro-1H-indazole 2-oxide (28 mg, 76.0 mmol, 88.1%) as a white solid. MS (M+H)+=369.1 (100% purity); 1H NMR (DMSO-d6) δ: 12.88 (br. s., 1H), 8.87 (s, 1H), 8.40 (s, 1H), 7.32 (s, 1H), 3.35 (s, 3H), 2.36-2.46 (m, 2H), 2.03 (br. s., 2H), 1.86-1.96 (m, 4H), 1.44 (s, 9H).

Workup

  1. concentrationthen concentrated
  2. dissolutionThe residue was re-dissolved in 5 mL of a solution of (dichloromethane/MeOH/ammonium hydroxide; 60:10:1)
  3. stirringstirred at 25° C. for 3 h
  4. customevaporated to a light yellow solid
  5. dissolutiondissolved in dichloromethane (added few drops MeOH and heating)
  6. custompurified by chromatography (spherical silica 20-45 μm, 23 g, Versaflash Supelco)
  7. washeluting with 0 to 10% over 15 min (MeOH containing 10% ammonium hydroxide)/dichloromethane
  8. customwas sonicated with hexanes
  9. customThe solid was separated by decantation
  10. customdried under high vacuum

Sources & evidence

ORD record
ord-37792258060b43638442d1be017351cf
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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