Trifluoroacetic acid → N-tert-butyl-2-(3-(methylsulfonyl)phenylamino)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 522971Notes

Reaction equation

HRID 522971 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:23]=[CH:22][CH:21]=[C:20]([S:24]([CH3:27])(=[O:26])=[O:25])[CH:19]=3)[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:23]=[CH:22][CH:21]=[C:20]([S:24]([CH3:27])(=[O:26])=[O:25])[CH:19]=3)[N:15]=2)[NH:10][CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 2

HCID 6422Trifluoroacetic acidHCID 131735556N-tert-butyl-2-(3-(methylsulfonyl)phenylamino)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 73295275N-tert-butyl-2-(3-(methylsulfonyl)phenylamino)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideYield 57%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×HCID 14923Ammonium HydroxideSolvent

Procedure

To a solution of N-tert-butyl-2-(3-(methylsulfonyl)phenylamino)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (61 mg, 118 mol) in dichloromethane (1.8 mL) was added trifluoroacetic acid (269 mg, 182 μL, 2.36 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 (1.8 mL), methanol (0.9 mL) and ammonium hydroxide (0.25 mL) and stirred at room temperature for 1 h. The mixture was concentrated and triturated with water. The solid was collected by filtration and washed with water and ether. Purification by chromatography (silica, GRADIENT UNKNOWN dichloromethane/methanol/0.5% ammonium hydroxide) gave N-tert-butyl-2-(3-(methylsulfonyl)phenylamino)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (26 mg, 67.1 mol, 57%) as a yellow solid. 1H NMR (400 MHz, DMSO-d) δ ppm: 12.42 (s, 1H), 9.87 (s, 1H), 8.33 (d, J=8.2, 1 H), 8.05 (d, J=3.4, 1 H), 8.03 (s, 1H), 7.79 (t, J=2.0, 1 H), 7.68 (s, 1H), 7.54 (t, J=8.0, 1 H), 7.47 (d, J=7.7, 1 H), 3.21 (s, 3H), 1.42 (s, 9H); MS (EI/CI) m/z: 388.2 [M+H].

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue obtained
  3. stirringstirred at room temperature for 1 h
  4. concentrationThe mixture was concentrated
  5. customtriturated with water
  6. filtrationThe solid was collected by filtration
  7. washwashed with water and ether
  8. customPurification by chromatography (silica, GRADIENT UNKNOWN dichloromethane/methanol/0.5% ammonium hydroxide)

Sources & evidence

ORD record
ord-689aa6b7278440bdb98555d9fc399094
Source dataset
uspto-grants-2016_05
Patent number
US09334278B2

Reaction notes

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