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

HRID 246410Notes

Reaction equation

HRID 246410 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[CH2:23][CH2:22][CH2:21][CH2:20][C:19]=4[N:18]([CH3:25])[N+:17]=3[O-:26])[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>ClCCl>[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[CH2:23][CH2:22][CH2:21][CH2:20][C:19]=4[N:18]([CH3:25])[N+:17]=3[O-:26])[N:14]=2)[NH:9][CH:8]=1)=[O:6])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 712804953-(7-(isopropylcarbamoyl)-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 1363594903-(7-(isopropylcarbamoyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)-1-methyl-4,5,6,7-tetrahydro-1H-indazole 2-oxideYield 82,112.102%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

To a pale yellow solution of 3-(7-(isopropylcarbamoyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)-1-methyl-4,5,6,7-tetrahydro-1H-indazole 2-oxide (45 mg, 92.8 μmol) in dichloromethane (2.00 mL) was added TFA (1.48 g, 1.00 mL, 13.0 mmo140), 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-(isopropylcarbamoyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)-1-methyl-4,5,6,7-tetrahydro-1H-indazole 2-oxide (27 mg, 76.2 mmol, 82.1%) as a white solid. MS (M+H)+=377 (100% purity); 1H NMR (DMSO-d6) δ: 12.93 (br. s., 1H), 8.93 (s, 1H), 8.45 (s, 1H), 7.45 (d, J=8.1 Hz, 1H), 4.13-4.33 (m, 1H), 3.35 (s, 3H), 2.37-2.46 (m, 2H), 1.83-2.18 (m, 6H), 1.22 (d, J=6.6 Hz, 6H).

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-7cb23ee01aa54e9d93416c9f89301222
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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