Pyridine → N-Isoxazol-3-yl-4-methyl-3-[7-(2-morpholin-4-ylethoxy)-1-oxoisoquinolin-2(1H)-yl]benzamide

4-Methyl-3-[7-(2-morpholin-4-ylethoxy)-1-oxoisoquinolin-2(1H)-yl]benzoic acid (708 mg) was dissolved in methylene chloride (5 ml) and DMF (3 drops) and cooled to 0° C. under an argon atmosphere. Oxalyl chloride (0.33 ml) was added and the reaction mixture stirred at room temperature for 2 hours. Pyridine (1.45 ml) and 3-aminoisoxazole (0.64 ml) were added and the reaction mixture stirred at room temperature for 2 hours. The reaction mixture was diluted with ethyl acetate, washed with 1N NaOH, dried (magnesium sulfate) and concentrated. Purification by column chromatography on an ion exchange column (isolute SCX column from International Sorbent Technology Limited, Henoed, Mid-Glamorgan, UK) using initially methanol and then a 99:1 mixture of methanol and aqueous ammonia solution to give an oily solid. The solid was triturated with ethyl acetate to give N-Isoxazol-3-yl-4-methyl-3-[7-(2-morpholin-4-ylethoxy)-1-oxoisoquinolin-2(1H)-yl]benzamide as a white solid (70 mg); NMR Spectrum: (DMSOd6) 2.15 (s, 3H), 2.50 (m, 4H), 2.75 (m, 2H), 3.55 (m, 4H), 4.20 (m, 2H), 6.75 (m, 1H), 7.05 (m, 1H), 7.25 (m, 1H), 7.45 (m, 1H), 7.60 (m, 1H), 7.70 (m, 2H), 8.00 (m, 2H), 8.85 (s, 1H), 11.45 (s, 1H); Mass Spectrum: M+H+ 475.

1. stirringthe reaction mixture stirred at room temperature for 2 hours
2. washwashed with 1N NaOH
3. dry with materialdried (magnesium sulfate)
4. concentrationconcentrated
5. customPurification by column chromatography on an ion exchange column (isolute SCX column from International Sorbent Technology Limited, Henoed, Mid-Glamorgan, UK)
6. additiona 99:1 mixture of methanol and aqueous ammonia solution
7. customto give an oily solid
8. customThe solid was triturated with ethyl acetate

ORD record

ord-7480050905bb427e9ee8a1a9ff748635

Source dataset

uspto-grants-2010_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07786115B2