反应详情

温度

45 °C

Pyridin-3-ylmethyl 3-ethynylazetidine-1-carboxylate (50 mg, 0.23 mmol), 3-iodo-4-methoxy-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine (40 mg, 0.11 mmol), allylpalladium chloride dimer (12 mg, 0.03 mmol), tri(2-furyl)phosphine (16 mg, 0.07 mmol) and copper (I) iodide (2.1 mg, 0.011 mmol) were combined into one vial fitted with a Teflon septum. The vial was flushed with nitrogen and acetonitrile (1.6 ml) and diisopropylamine (0.048 mL, 0.34 mmol) were added. After sparging with nitrogen for 5 minutes, the reaction was heated to 45° C. for two hours. The mixture was cooled to ambient temperature, diluted with ethyl acetate and washed with saturated aqueous sodium bicarbonate. The organic layer was separated and the aqueous layer was back extracted with ethyl acetate two times. The combined organic layers were dried over sodium sulfate, filtered and concentrated. The residue was purified by preparative HPLC reverse phase (C-18), eluting with acetonitrile/water+0.05% TFA. The fractions containing product were combined and diluted in ethyl acetate, then washed with aqueous sodium bicarbonate and dried over sodium sulfate. The solution was filtered and concentrated under reduced pressure to give pyridin-3-ylmethyl 3-{[4-methoxy-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridin-3-yl]ethynyl}azetidine-1-carboxylate. 1H NMR (500 MHz, DMSO-d6) δ 8.63 (s, 1H), 8.58 (s, 1H), 8.50-8.54 (m, 1H), 8.29 (s, 1H), 8.02 (s, 2H), 7.74-7.82 (m, 1H), 7.35-7.43 (m, 1H), 6.94 (s, 1H), 5.09 (s, 2H), 4.12-4.38 (br, 2H), 3.80-3.98 (m, 8H), 3.67-3.76 (m, 1H). LRMS (ESI) calculated for C24H23N6O3 [M+H]+, 443.2; found 443.2.

1. additionwere added
2. customAfter sparging with nitrogen for 5 minutes
3. temperatureThe mixture was cooled to ambient temperature
4. additiondiluted with ethyl acetate
5. washwashed with saturated aqueous sodium bicarbonate
6. customThe organic layer was separated
7. extractionthe aqueous layer was back extracted with ethyl acetate two times
8. dry with materialThe combined organic layers were dried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated
11. customThe residue was purified by preparative HPLC reverse phase (C-18)
12. washeluting with acetonitrile/water+0.05% TFA
13. additionThe fractions containing product
14. additiondiluted in ethyl acetate
15. washwashed with aqueous sodium bicarbonate
16. dry with materialdried over sodium sulfate
17. filtrationThe solution was filtered
18. concentrationconcentrated under reduced pressure