反应详情

(Steps 1-v & 1-yl) tert-Butyl (R)-1-(6-(3-chlorophenylamino)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethylcarbamate (110 mg, 0.28 mmol) was dissolved in 5 mL TFA/CH2Cl2 (1:1) and left standing for 20 min. The solvent was removed under reduced pressure and CH2Cl2 was added and removed 4 times to remove residual TFA. The resulting amine was dissolved in DMF and 3-aminopyrazine-2-carboxylic acid (200 mg, 1.4 mmol), HBTU (0.50 g, 1.3 mmol) and DIEA (1 mL, 5.7 mmol) were added. The reaction mixture was stirred at room temperature for 2 hours, then poured into ethyl acetate/0.1 M NaOH. The organic layer was dried over sodium sulfate and concentrated to yield an oil. This oil was purified by reversed-phase HPLC. Fractions containing pure product were concentrated to give N—((R)-1-(6-(3-chlorophenylamino)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethyl)-3-aminopyrazine-2-carboxamide as a yellow solid (60 mg, 0.13 mmol, 48% yield): 1H NMR (500 MHz, DMSO-d6) 10.43 (s, 1H), 9.19 (d, J=8.1 Hz, 1H), 8.22-8.20 (m, 2H), 7.89 (t, J=2.0 Hz, 1H), 7.75-7.73 (m, 2H), 7.33 (m, 2H), 7.07 (dd, J=1.3, 7.9 Hz, 1H), 5.76-5.71 (m, 1H), 1.75 (d, J=6.9 Hz, 3H); MH+410.2.

1. waitleft
2. customThe solvent was removed under reduced pressure and CH2Cl2
3. additionwas added
4. customremoved 4 times
5. customto remove residual TFA
6. dissolutionThe resulting amine was dissolved in DMF
7. dry with materialThe organic layer was dried over sodium sulfate
8. concentrationconcentrated
9. customto yield an oil
10. customThis oil was purified by reversed-phase HPLC
11. additionFractions containing pure product
12. concentrationwere concentrated