2-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl → HCID 66670528, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of (R)-3-[6-(6-Chloro-pyrazolo[1,5-a]pyridin-3-yl)-pyrazin-2-ylamino]-piperidine-1-carboxylic acid tert-butyl ester (129 mg, 0.3 mmol), zinc cyanide (40 mg, 0.342 mmol), S-Phos (11.1 mg, 0.027 mmol) and Pd2(dba)3 (11 mg, 0.012 mmol) in DMF-water (1.36 ml, 99:1 DMF:water) was degassed for 5 min then back filled with nitrogen. The reaction mixture was then heated to 150° C. in a microwave reactor for 30 min. The crude reaction mixture was diluted with 2N NaOH (1 ml) and ethyl acetate (10 ml). The aqueous layer was back extracted with ethyl acetate (10 ml), then the pooled ethyl acetate phases were washed with brine and dried with sodium sulfate and concentrated in vacuo to an oil. The crude oil was purified by column chromatography (0-100% ethyl acetate in heptane) which gave (R)-3-[6-(6-cyano-pyrazolo[1,5-a]pyridin-3-yl)-pyrazin-2-ylamino]-piperidine-1-carboxylic acid tert-butyl ester as a greenish oil (70 mg). (R)-3-[6-(6-cyano-pyrazolo[1,5-a]pyridin-3-yl)-pyrazin-2-ylamino]-piperidine-1-carboxylic acid tert-butyl ester (70 mg, 0.167 mmol) was dissolved in anhydrous DCM (2 ml) then 4 N HCl in dioxane (0.417 mL, 10 eq.) was added. The resulting mixture was capped and stirred at 23° C. After 4 h the reaction mixture was concentrated which gave the title compound 21 as a light yellow solid (64 mg). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.54-1.68 (m, 1H) 1.79-2.01 (m, 2H) 2.01-2.16 (m, 1H) 2.78-3.05 (m, 2H) 3.19-3.30 (m, 1H) 3.44 (none, 1H) 4.27 (br. s., 1H) 7.68 (d, J=8.59 Hz, 1H) 7.84 (s, 1H) 8.38 (s, 1H) 8.54 (d, J=9.35 Hz, 1H) 8.98 (s, 1H) 9.67 (s, 1H); LCMS M+1 320.2.

Provenance & Evidence