反应详情

(R)-(Tetrahydrofuran-2-yl)methanol (22 mg, 0.214 mmol) was added to a solution of NaH (10 mg, 0.246 mmol) in dry DMF (1 mL) in a 2-necked flask under Nitrogen. Another portion of NaH (10 mg, 0.246 mmol) was added to a stirring solution of 1-((6-fluoropyridin-2-yl)methyl)-N-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine (Example 170) (50 mg, 0.154 mmol) in DMF (1 ml). This solution was added to the 2-necked flask and stirred for 16 h at rt. The reaction was quenched with NH4Cl (sat. solution, 1 mL) and diluted with Ethyl Acetate (20 mL). The organics were separated and washed with NaHCO3 (sat. solution, 20 mL). The aqueous phase was re-extracted with Ethyl Acetate (2×10 mL). The combined organics were dried over Na2SO4, filtered and the solvent evaporated to give a crude product that was purified by prep HPLC. (R)—N-(1-methyl-1H-pyrazol-4-yl)-1-((6-((tetrahydrofuran-2-yl)methoxy)pyridin-2-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine was obtained as a white solid (24 mg, 38% yield). 1H NMR (d6-Acetone) δ 8.87 (s, 1H), 8.04 (s, 1H), 7.99 (s, 1H), 7.61 (s and t, 2H), 6.70 (d, 1H), 6.64 (d, 1H), 5.54 (s, 2H), 4.07 (m, 3H), 3.82 (s, 3H), 3.75 (m, 1H), 3.61 (m, 1H), 1.84 (m, 3H), 1.54 (m, 1H); LC-MS method B, (ES+) 407.1, RT=7.65 min.

1. additionThis solution was added to the 2-necked flask
2. customThe reaction was quenched with NH4Cl (sat. solution, 1 mL)
3. additiondiluted with Ethyl Acetate (20 mL)
4. customThe organics were separated
5. washwashed with NaHCO3 (sat. solution, 20 mL)
6. extractionThe aqueous phase was re-extracted with Ethyl Acetate (2×10 mL)
7. dry with materialThe combined organics were dried over Na2SO4
8. filtrationfiltered
9. customthe solvent evaporated
10. customto give a crude product that
11. customwas purified by prep HPLC