反应详情

In an alternate preparation of the above titled compound previously described in Examples 135 and 143, N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N′-[(6-fluoro-3′-formyl-3-biphenylyl)methyl]butanediamide (36.9 mg. 0.06 mmol) was diluted in DMSO (1.5 mL) and dispensed into a 1 dram vial containing 1,1-dimethylethyl (2S)-2-methyl-1-piperazinecarboxylate (0.18 mmol) and acetic acid (3.6 mg, 0.6 mmol) and fitted with a magnetic stir bar. The resulting solution was stirred at room temperature for 4 h. MP-B(OAc)3H (0.6 mmol, 140 mg) was added and the solution was stirred for another 12 h. The polymer reagent was filtered off and to the filtrate were added MeOH (2.0 mL) and 1 drop of concentrated HCl. This solution was heated at 60 C. ° for 12 h. Purification was completed via reverse phase HPLC using a Gilson (acidic conditions with 0.1% TFA in the solvents). The product after HPLC purification was dissolved in 3 mL of MeOH and passed through a 0.5 g amine column (washed with 8 mL of MeOH) to afford 16.3 mg of the title compound (38.9%). LC-MS m/z 700 (M+H)+, 0.66 min (ret time).

1. customfitted with a magnetic stir bar
2. stirringthe solution was stirred for another 12 h
3. filtrationThe polymer reagent was filtered off and to the filtrate
4. additionwere added MeOH (2.0 mL) and 1 drop of concentrated HCl
5. temperatureThis solution was heated at 60 C
6. wait° for 12 h
7. customPurification
8. customThe product after HPLC purification
9. dissolutionwas dissolved in 3 mL of MeOH
10. washpassed through a 0.5 g amine column (washed with 8 mL of MeOH)