Yield:58364-91-3 68.8%

Reaction Conditions:

with potassium carbonate in N,N-dimethyl-formamide at 0 - 20;Inert atmosphere;

Steps:

134.134A

Example 134; (S, E)-Methyl 4-(6-(l-(3-(5-chloro-2-(1H-tetrazol-1-yl)phenyl)acrylamido)-2-(5- methoxy-1-methyl-1H-pyrazol-3-yl)ethyl)-3-oxo-2_>3-dihydropyridazin-4- yl)phenylcarbamate; 134 A. methyl 5 -methoxy-1 -methyl- 1H-pyrazole-3-carboxylate: To a cooled solution (0 °C) of methyl 5-hydroxy-1-methyl-1H-pyrazole-3-carboxylate (1.60 g, 10.25 mmol) and K₂CO₃ (2.124 g, 15.37 mmol) in DMF (10 mL) was added dropwise MeI (0.703 mL, 11.27 mmol). The reaction mixture was stirred under argon at rt for 5 days. The reaction mixture was diluted with EtOAc, washed with H₂O (1 x 15 mL), saturated NaHCO₃ (1 x 15 mL) and brine (1 x 15 mL). The organic phase was dried over MgSO^ filtered an Purification by normal phase chromatography gave 134A (1.20 g, 7.05 mmol, 68.8 % yield) as a white solid. LC- MS (ESI) m/z: 171.2(M+H)⁺.

References:

WO2009/114677,2009,A1 Location in patent:Page/Page column 209-210