Trifluoroacetic acid → HCID 73295443, compound

HRID 522969Notes

Reaction equation

HRID 522969 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][C:21]([CH3:24])=[CH:20][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][C:21]([CH3:24])=[CH:20][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 131735555HCID 131735555, compound

Product 1

HCID 73295443HCID 73295443, compoundYield 30%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×HCID 14923Ammonium HydroxideSolvent

Procedure

To a solution of N-tert-butyl-2-(p-tolylamino)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (80 mg, 176 μmol) in dichloromethane (3 mL) was added trifluoroacetic acid (402 mg, 272 μL, 3.53 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 (3 mL), methanol (1.5 mL) and ammonium hydroxide (0.4 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, 20-40% of a 10:89.5:0.5 methanol:dichloromethane:ammonium hydroxide solution in dichloromethane) gave N-tert-butyl-2-(p-tolylamino)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (17 mg, 52.6 μmol, 30%) as a light yellow solid. 1H NMR (400 MHz, DMSO-d) δ ppm: 12.26 (s, 1H), 9.34 (s, 1H), 7.97 (s, 1H), 7.96 (d, J=3.3, 1 H), 7.76 (s, 1H), 7.57 (t, J=8.5, 2 H), 7.09 (d, J=8.1, 2 H), 2.26 (s, 3H), 1.44 (s, 9H); MS (EI/CI) m/z: 324.1 [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, 20-40% of a 10:89.5:0.5 methanol:dichloromethane:ammonium hydroxide solution in dichloromethane)

Sources & evidence

ORD record
ord-96012682f6984f1090e1b3636a82048a
Source dataset
uspto-grants-2016_05
Patent number
US09334278B2

Reaction notes

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