1-(bromomethyl)-4-[(2-methylpropan-2-yl)oxy]benzene

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3-(8-Amino-3-cyclobutyl-imidazo[1,5-a]pyrazin-1-yl)-phenol (200 mg, 0.71 mmol) in DMF (3.5 mL) was charged with Cs2CO3 (348 mg, 1.07 mmol) and stirred at rt for 30 min. A solution of 1-bromomethyl-4-tert-butoxy-benzene (162 mg, 0.71 mmole) in 0.5 mL of DMF, was added to the reaction mixture. After 15 h, the reaction was complete by LC/MS analysis. The product was an orange/brown solid. The crude product was chromatographed on silica gel [Jones Flashmaster, 5 g cartridge, eluting with 10% ethyl acetate]. The product was then recrystalized with ethyl acetate and hexanes yielding the title compound as a white solid; 1H NMR (CDCl3, 400 MHz) δ 1.36 (s, 9H), 2.11-2.23 (m, 2H), 2.45-2.52 (m, 2H), 2.59-2.69 (m, 2H), 3.77-3.85 (m, 1H), 5.08 (s, 2H), 5.49 (brs, 2H), 7.01-7.04 (m, 3H), 7.05 (dd, J=4.00 Hz, 1H), 7.10 (d, J=5.02 Hz, 1H), 7.23-7.25 (m, 1H), 7.29 (q, J=40 Hz, 1H), 7.34-7.36 (m, 2H), 7.41 (t, J=16 Hz, 1H); MS (ES+): m/z 443.04 (100) [MH+]. After 15 h The crude product was chromatographed on silica gel [Jones Flashmaster, 5 g cartridge, eluting with 10% ethyl acetate] The product was then recrystalized with ethyl acetate and hexanes yielding the title compound as a white solid

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3-(8-Amino-3-cyclobutyl-imidazo[1,5-a]pyrazin-1-yl)-phenol (200 mg, 0.71 mmol) in DMF (3.5 mL) was charged with Cs2CO3 (348 mg, 1.07 mmol) and stirred at rt for 30 min. A solution of 1-bromomethyl-4-tert-butoxy-benzene (162 mg, 0.71 mmole) in 0.5 mL of DMF, was added to the reaction mixture. After 15 h, the reaction was complete by LC/MS analysis. The product was an orange/brown solid. The crude product was chromatographed on silica gel [Jones Flashmaster, 5 g cartridge, eluting with 10% ethyl acetate]. The product was then recrystalized with ethyl acetate and hexanes yielding the title compound as a white solid; 1H NMR (CDCl3, 400 MHz) δ 1.36 (s, 9H), 2.11-2.23 (m, 2H), 2.45-2.52 (m, 2H), 2.59-2.69 (m, 2H), 3.77-3.85 (m, 1H), 5.08 (s, 2H), 5.49 (brs, 2H), 7.01-7.04 (m, 3H), 7.05 (dd, J=4.00 Hz, 1H), 7.10 (d, J=5.02 Hz, 1H), 7.23-7.25 (m, 1H), 7.29 (q, J=40 Hz, 1H), 7.34-7.36 (m, 2H), 7.41 (t, J=16 Hz, 1H); MS (ES+): m/z 443.04 (100) [MH+]. After 15 h The crude product was chromatographed on silica gel [Jones Flashmaster, 5 g cartridge, eluting with 10% ethyl acetate] The product was then recrystalized with ethyl acetate and hexanes yielding the title compound as a white solid

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3-(8-Amino-3-cyclobutyl-imidazo[1,5-a]pyrazin-1-yl)-phenol (200 mg, 0.71 mmol) in DMF (3.5 mL) was charged with Cs2CO3 (348 mg, 1.07 mmol) and stirred at rt for 30 min. A solution of 1-bromomethyl-4-tert-butoxy-benzene (162 mg, 0.71 mmole) in 0.5 mL of DMF, was added to the reaction mixture. After 15 h, the reaction was complete by LC/MS analysis. The product was an orange/brown solid. The crude product was chromatographed on silica gel [Jones Flashmaster, 5 g cartridge, eluting with 10% ethyl acetate]. The product was then recrystalized with ethyl acetate and hexanes yielding the title compound as a white solid; 1H NMR (CDCl3, 400 MHz) δ 1.36 (s, 9H), 2.11-2.23 (m, 2H), 2.45-2.52 (m, 2H), 2.59-2.69 (m, 2H), 3.77-3.85 (m, 1H), 5.08 (s, 2H), 5.49 (brs, 2H), 7.01-7.04 (m, 3H), 7.05 (dd, J=4.00 Hz, 1H), 7.10 (d, J=5.02 Hz, 1H), 7.23-7.25 (m, 1H), 7.29 (q, J=40 Hz, 1H), 7.34-7.36 (m, 2H), 7.41 (t, J=16 Hz, 1H); MS (ES+): m/z 443.04 (100) [MH+]. After 15 h The crude product was chromatographed on silica gel [Jones Flashmaster, 5 g cartridge, eluting with 10% ethyl acetate] The product was then recrystalized with ethyl acetate and hexanes yielding the title compound as a white solid