LY 2157299 synthesis

Yield:700874-72-2 63.8%

Reaction Conditions:

with ammonia in methanol at 90; under 4137.29 Torr; for 66 h;

Steps:

2.G G. Preparation of 2- (6-METHYL-PYRIDIN-2-YL)-3- [6-AMIDO-QUINOLIN-4-YL)-5, 6- DIHYDRO-4H-PYRROLO [1, 2-B] PYRAZOLE
Warm a mixture OF 4- [2- (6-METHYL-PYRIDIN-2-YL)-5, 6-dihydro-4H-pyrrolo [1, 2- B] PYRAZOL-3-YL] -QUINOLINE-6-CARBOXYLIC ACID METHYL ESTER IN 60 ML 7 N AMMONIA IN methanol to 90 °C in a stainless steel pressure vessel for 66 hours. The pressure will rise to about 80 PSI. Maintain the pressure for the duration of the reaction. Cool the vessel and concentrate the brown mixture in vacuo. Purify the residual solid on two 12 g Redi- Pak cartridges coupled in series eluting with acetone. Combine appropriate fractions and concentrate in vacuo. Suspend the resulting nearly white solid in methylene chloride, dilute with hexane, and filter. The collected off-white solid yields 1.104 g (63.8%) of the desired title product. MS ES+ = 370 (M+1).

References:

ELI LILLY AND COMPANY WO2004/48382, 2004, A1 Location in patent:Page 10

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