BAY-474 synthesis

Yield:1033767-86-0 57.6%

Reaction Conditions:

with acetic acid at 20;Heating / reflux;

Steps:

14

SYNTHETIC EXAMPLE 14A mixture of 17.0 g (106.13 mmol) 3-methyl-1 H-indazole-5-carbaldehyde, from Synthetic Preparation 10, and 17.86 g (217.57 mmol) 3-aminocrotononitrile were dissolved in 340 mL acetic acid and refluxed for 3 hours. After stirring overnight at room temperature the mixture was cooled with an ice bath, filtered and washed with a small amount of acetic acid. The product was dried under vacuum at 60⁰C to afford 1 ,4-dihydro-2,6-dimethyl-4-(3- methyl-1H-indazol-5-yl)-3,5-pyridinedicarbonitrile (17.7 g, 57.6 %) (Cpd. No. 81, Table 2). 1 H-NMR (DMSO-D6): δ = 12.68 (s, 1 H), 9.51 (s, 1 H)₁ 7.53 (s, 1H)₁ 7.49 (d, 1 H), 7.27 (d, 1 H)₁ 4.50 (s, 1 H), 2.49 (s, 3H), 2.05 (s, 6H) ppm. MS (ES+): 290.42 (M⁺+1 , 100 %).

References:

WO2008/71451,2008,A1 Location in patent:Page/Page column 64-65