反应详情

温度

40 °C

[4-{4-[7-((1R,2R,3S,4S)-3-Carbamoyl-bicyclo[2.2.1]hept-5-en-2-ylamino)-6-chloro-3H-imidazo[4,5-b]pyridin-2-yl]-benzyl}-piperazine-1-carboxylic acid tert-butyl ester (159.0 mg, 0.2750 mmol) was taken up into Methylene chloride (8.4 mL, 130 mmol) and treated with Trifluoroacetic Acid (3 mL, 40 mmol) and stirred @ 40° C., O/N. The solution was then concentrated. The residue was taken up into methanol and treated with 900 mg mp carbonate for ½ hour. The resin was removed by filtration and filtrate concentrated. The residue was taken up into DCM/THF (˜30 mL) and Acetic anhydride (0.56 mL, 5.9 mmol) was added followed by triethylamine Triethylamine (0.56 mL, 4.0 mmol). Solution was stirred at RT for 1 hr and then concentrated. The residue was purified via reverse phase chromotography using a gradient of MeCN with 0.1% TFA in Water with 0.1% TFA on a Phenomenex Gemini-NX C18 AXIA column. Fractions containing desired product were poured into sat'd sodium bicarbonate and extracted with 3 portions of methylene chloride. The combined organic was dried over magnesium sulfate, filtered and evaporated to yield a yellow solid, 15.00 mg, 10% yield. (300 MHz, DMSO-d6) 13.26 (s, 1H), 8.10 (d, J=8 Hz, 2H), 7.95 (s, 1H), 7.78 (m, 1H), 7.48 (d, J=8 Hz, 2H), 7.22 (m, 2H), 6.44-6.33 (m, 2H), 5.17 (t, J=17 Hz, 9 Hz, 1H), 3.56 (s, 2H), 3.43 (m, 4H), 2.89 (s, 1H), 2.80 (s, 1H), 2.62 (d, J=9 Hz, 1H), 2.40 (m, 2H), 2.33 (m, 2H), 2.25 (d, J=8 Hz, 1H), 1.98 (s, 3H), 1.38 (d, J=8 Hz, 1H). MS=521 (M+H), HPLC: 1.47 min. (G Method)

1. concentrationThe solution was then concentrated
2. additiontreated with 900 mg mp carbonate for ½ hour
3. customThe resin was removed by filtration and filtrate
4. concentrationconcentrated
5. additionwas added
6. stirringSolution was stirred at RT for 1 hr
7. concentrationconcentrated
8. customThe residue was purified via reverse phase chromotography
9. additionFractions containing desired product
10. additionwere poured into sat'd sodium bicarbonate
11. extractionextracted with 3 portions of methylene chloride
12. dry with materialThe combined organic was dried over magnesium sulfate
13. filtrationfiltered
14. customevaporated
15. customto yield a yellow solid, 15.00 mg, 10% yield
16. custom1.47 min. (G Method)