Sodium Hydroxide → 4-[4-[5-Amino-6-[3-[4-(methylaminomethyl)phenyl]isoxazol-5-yl]pyrazin-2-yl]-2-pyridyl]tetrahydropyran-4-carboxamide

Participants

Reaction Conditions

Reaction Steps

4-[4-[5-amino-6-[3-[4-(methylaminomethyl)phenyl]isoxazol-5-yl]pyrazin-2-yl]-2-pyridyl]tetrahydropyran-4-carbonitrile (Trifluoroacetic Acid (1)) (18 mg, 0.03002 mmol) was dissolved in methanol (1 mL) and then 1 M sodium hydroxide solution (300.2 μL of 1 M, 0.3002 mmol) was added. The reaction mixture was heated in the microwave to 100° C. for 45 minutes. The reaction mixture was diluted with water and extracted with ethyl acetate. The extracted organic layer was dried over MgSO4, filtered and concentrated in vacuo to a solid. Compound was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 mM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% trifluoroacetic acid in water; solvent B: acetonitrile) over 16 minutes at 25 mL/minutes], combined fractions were then freeze-dried to give 4-[4-[5-amino-6-[3-[4-(methylaminomethyl)phenyl]isoxazol-5-yl]pyrazin-2-yl]-2-pyridyl]tetrahydropyran-4-carboxamide Compound I-13 as a yellow solid (6 mg, 31.37%). 1H NMR (400.0 MHz, DMSO-d6) δ 2.2-2.25 (m, 2H), 2.45-2.5 (m, 2H), 2.65-2.7 (m, 3H), 3.6-3.75 (m, 4H), 4.28-4.33 (m, 2H), 7.18-7.2 (m, 1H), 7.27-7.3 (m, 1H), 7.35-7.39 (m, 1H), 7.7 (d, 2H), 7.85 (s, 1H), 8.05 (d, 1H), 8.1 (s, 1H), 8.18 (d, 2H), 8.7 (d, 1H), 8.88 (br s, 2H), 9.05 (s, 1H); LC/MS m/z 486.2 [M+H]+.

Provenance & Evidence