Isolera snap 10 g

Example 62

[Figure (not displayed)]

5-Bromo-1-((6-methoxypyridin-3-yl)methyl)-N-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide (150 mg, 0.426 mmol), cobalt carbonyl (36.4 mg, 0.106 mmol), DMAP (104 mg, 0.852 mmol), palladium (II) acetate (4.78 mg, 0.021 mmol), cyclopropanamine (24.32 mg, 0.426 mmol) and xantphos (12.32 mg, 0.021 mmol) were added to a microwave vial. The vial was sealed, THF (3.3 mL) added and the reaction mixture was heated in a Biotage Initiator microwave at 80° C. for 30 min. The resulting mixture was diluted with water (20 mL) and extracted with ethyl acetate (20 mL). The organic layer was dried, concentrated under vacuum and purified by MDAP (High pH), the appropriate fractions were combined and concentrated under vacuum. The resulting product was loaded in DCM and purified by Biotage Isolera SNAP 10 g silica flash chromatography using a gradient of 0-60% cyclohexane/ethyl acetate. The product containing fractions were combined and concentrated under vacuum to give the product (64 mg) as a white solid.

LCMS (2 min Formic): Rt=0.72 min, [MH]⁺=357.1

Example 62

[Figure (not displayed)]

5-Bromo-1-((6-methoxypyridin-3-yl)methyl)-N-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide (150 mg, 0.426 mmol), cobalt carbonyl (36.4 mg, 0.106 mmol), DMAP (104 mg, 0.852 mmol), palladium (II) acetate (4.78 mg, 0.021 mmol), cyclopropanamine (24.32 mg, 0.426 mmol) and xantphos (12.32 mg, 0.021 mmol) were added to a microwave vial. The vial was sealed, THF (3.3 mL) added and the reaction mixture was heated in a Biotage Initiator microwave at 80° C. for 30 min. The resulting mixture was diluted with water (20 mL) and extracted with ethyl acetate (20 mL). The organic layer was dried, concentrated under vacuum and purified by MDAP (High pH), the appropriate fractions were combined and concentrated under vacuum. The resulting product was loaded in DCM and purified by Biotage Isolera SNAP 10 g silica flash chromatography using a gradient of 0-60% cyclohexane/ethyl acetate. The product containing fractions were combined and concentrated under vacuum to give the product (64 mg) as a white solid.

LCMS (2 min Formic): Rt=0.72 min, [MH]⁺=357.1

Example 55

[Figure (not displayed)]

5-Bromo-1-(2-fluoro-3-methylbenzyl)-N-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide (200 mg, 0.566 mmol), cobalt carbonyl (48.4 mg, 0.142 mmol), DMAP (138 mg, 1.133 mmol), palladium (II) acetate (6.36 mg, 0.028 mmol), cyclopropylamine (0.040 mL, 0.566 mmol) and xantphos (16.38 mg, 0.028 mmol) were added to a microwave vial. The vial was sealed and THF (3.3 mL) added and the reaction mixture was then heated in a Biotage Initiator microwave at 80° C. for 30 min. The resulting mixture was diluted with water (20 mL) and extracted with ethyl acetate (20 mL). The organic layer was dried, concentrated under vacuum and purified by MDAP (High pH), the appropriate fractions were combined and concentrated under vacuum. The resulting product was loaded in DCM and purified by purified by Biotage Isolera SNAP 10 g silica flash chromatography using a gradient of 0-60% cyclohexane/ethyl acetate. The product containing fractions were combined and concentrated under vacuum to give the desired product (50 mg) as a white solid.

LCMS (2 min Formic): Rt=0.91 min, [MH]⁺=358.1.