Trifluoroacetic acid → N-tert-butyl-2-(1,5-dimethyl-1H-pyrazol-4-ylamino)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 522977Notes

Reaction equation

HRID 522977 reaction equation
[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([NH:17][C:18]3[CH:19]=[N:20][N:21]([CH3:24])[C:22]=3[CH3:23])[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.CO.[OH-].[NH4+]>[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([NH:17][C:18]3[CH:19]=[N:20][N:21]([CH3:24])[C:22]=3[CH3:23])[N:15]=2)[NH:10][CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 2

HCID 6422Trifluoroacetic acidHCID 90040996N-tert-butyl-2-(1,5-dimethyl-1H-pyrazol-4-ylamino)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 73295612N-tert-butyl-2-(1,5-dimethyl-1H-pyrazol-4-ylamino)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideYield 56%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×HCID 14923Ammonium HydroxideSolvent

Procedure

To a solution of N-tert-butyl-2-(1,5-dimethyl-1H-pyrazol-4-ylamino)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (45 mg, 98.3 μmol) in dichloromethane (1.5 mL) was added trifluoroacetic acid (224 mg, 152 μL, 1.97 mmol) and the mixture stirred at room temperature for 16 h. The reaction mixture was concentrated in vacuo and the residue obtained diluted with dichloromethane (1.5 mL), methanol (0.75 mL) and ammonium hydroxide (0.2 mL) and stirred at room temperature for 2 h. The reaction mixture was concentrated then purified by chromatography (silica, 10-45% of a 1:4 methanol:dichloromethane solution in dichloromethane) to give N-tert-butyl-2-(1,5-dimethyl-1H-pyrazol-4-ylamino)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (18 mg, 55.0 μmol, 56%) as a yellow solid. 1H NMR (400 MHz, DMSO-d) δ ppm: 12.10 (s, 1H), 8.39 (s, 1H), 7.87 (s, 1H), 7.86 (s, 1H), 7.85 (d, J=3.3, 1 H), 3.71 (s, 3H), 2.16 (s, 3H), 1.30 (s, 9H); MS (EI/CI) m/z: 328.2 [M+H].

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue obtained
  3. stirringstirred at room temperature for 2 h
  4. concentrationThe reaction mixture was concentrated
  5. customthen purified by chromatography (silica, 10-45% of a 1:4 methanol:dichloromethane solution in dichloromethane)

Sources & evidence

ORD record
ord-01d22eee68064624a1bb4fba234ec9f9
Source dataset
uspto-grants-2016_05
Patent number
US09334278B2

Reaction notes

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