Phosphorus oxychloride → 1-(3-Benzyloxyphenyl)-3-tert-butylimidazo[1,5-a]pyrazin-8-ylamine
Reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:15]2[N:16]=[C:17]([C:25]([CH3:28])([CH3:27])[CH3:26])[N:18]3[CH:23]=[CH:22][N:21]=[C:20](Cl)[C:19]=23)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O=P(Cl)(Cl)Cl.C(OC1C=C(C(C2C(Cl)=NC=CN=2)[NH:49]C(=O)C(C)(C)C)C=CC=1)C1C=CC=CC=1>>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:15]2[N:16]=[C:17]([C:25]([CH3:28])([CH3:27])[CH3:26])[N:18]3[CH:23]=[CH:22][N:21]=[C:20]([NH2:49])[C:19]=23)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1Participants
Conditions
- Temperature
- 55 °C
Procedure
1-(3-Benzyloxyphenyl)-3-tert-butyl-8-chloroimidazo[1,5-a]pyrazine: A mixture of POCl3 (3 mL, 5 g, 33 mmol) and N-[(3-benzyloxyphenyl)-(3-chloropyrazin-2-yl)-methyl]-2,2-dimethylpropionamide (109 mg, 0.266 mmol) is heated to 55° C. for 6 d. POCl3 is evaporated, a cold solution of NH3 in iPrOH (2 M, 5 mL) is added, the suspension is filtered, and the solid is washed with iPrOH. The crude material contained in the combined filtrate and washings is adsorbed onto Hydromatrix and chromatographed on silica gel [Jones Flashmaster, 10 g/70 mL cartridge, eluting with hexanes:EtOAc 10:1 (1-22)→5:1 (23-40)], yielding the title compound as yellow oil that slowly solidifies; 1H NMR (CDCl3, 400 MHz) δ 1.59 (s, 9H), 5.13 (s, 2H), 7.03 (d, J=8.0 Hz, 1H), 7.27-7.42 (m, 7H), 7.46 (d, J=7.2 Hz, 2H), 7.87 (d, J=4.8 Hz, 1H). MS (ES+): m/z 392.1/394.0 (12/4) [MH+].
Workup
- customPOCl3 is evaporated
- additiona cold solution of NH3 in iPrOH (2 M, 5 mL) is added
- filtrationthe suspension is filtered
- washthe solid is washed with iPrOH
- customchromatographed on silica gel [Jones Flashmaster, 10 g/70 mL cartridge, eluting with hexanes:EtOAc 10:1 (1-22)→5:1 (23-40)]
Sources & evidence
- ORD record
- ord-88521a9fc5c64d85aa69930f9f158043
- Source dataset
- uspto-grants-2008_12
- Patent number
- US07459554B2
Reaction notes
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