Hydrochloric Acid → 5-(4-Bromo-2-fluorophenylamino)-N-(2-hydroxy-ethoxy)-imidazo[1,5-a]pyrazine-6-carboxamide
Reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:14]3[CH:15]=[N:16][CH:17]=[C:13]3[CH:12]=[N:11][C:10]=2[C:18]([NH:20][O:21][CH2:22][CH2:23][O:24]C=C)=[O:19])=[C:4]([F:27])[CH:3]=1.Cl.O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+]>CO.ClCCl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:14]3[CH:15]=[N:16][CH:17]=[C:13]3[CH:12]=[N:11][C:10]=2[C:18]([NH:20][O:21][CH2:22][CH2:23][OH:24])=[O:19])=[C:4]([F:27])[CH:3]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
A solution of 5-(4-bromo-2-fluorophenylamino)-N-(2-(vinyloxy)ethoxy)-imidazo[1,5-a]pyrazine-6-carboxamide (150 mg, 0.34 mmol) in methanol (4.5 mL) and dichloromethane (8.9 mL) was added 4M HCl in 1,4-dioxane (0.13 mL, 0.5 mmol, 1.5 eq.), and the reaction mixture was stirred at ambient temperature under N2 for 1 h. Solid sodium carbonate (50 mg) was added to the reaction mixture. The reaction mixture was absorbed onto silica and then subjected to flash chromatography (Si-PPC, gradient 0% to 15%, methanol in dichloromethane) to afford the title compound as a white solid. (112.1 mg, 79.5%). 1H NMR (DMSO-d6, 400 MHz) δ ppm 11.85 (broad s, 1H), 10.32 (broad s, 1H), 8.83 (s, 1H), 7.97 (s, 1H), 7.92 (s, 1H), 7.64 (dd, J=10.4 Hz, 2.6 Hz, 1H), 7.30 (d, J=8.8 Hz, 1H), 6.77 (t, J=8.8 Hz, 1H), 4.68 (t, J=5.6 Hz, 1H), 3.89 (t, 4.8 Hz, 2H), 3.59 (q, J=5.4 Hz, 2H); LCMS (method D1): RT=0.786 min, [M+H]+=410/412.
Workup
- customThe reaction mixture was absorbed onto silica
Sources & evidence
- ORD record
- ord-35b4ce8456584471a02f65d7e67afe35
- Source dataset
- uspto-grants-2012_10
- Patent number
- US08288408B2
Reaction notes
Loading…