反应详情

温度

50 °C

A solution of methyl 3-(chloromethyl)-1-(4-fluorobenzyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxylate (24 mL, 2.0M in CH2Cl2, 48.3 mmol) [prepared as described in step 2 of example 40] was evaporated in vacuo to a residue. To this residue, anhydrous DMF (150 mL) and piperazin-2-one (386.4 mmol, 38.689, 8.0 eq.) were added followed by i-Pr2NEt (18.77 g, 145.2 mmol, 25.29 mL, 3 eq.). The mixture, under nitrogen, was placed in an oil bath and the bath was warmed to 50° C. After stirring for 4 hours (50° C.) the reaction was judged to be complete by HPLC-MS analysis. The volatiles were removed in vacuo (ca. 2 torr, at 60° C.) to give a yellow residue. Saturated aqueous sodium bicarbonate (300 mL) was added. White solid precipitated out, and the mixture was sonicated for 30 min and cooled to 10° C. The solid was filtered, washed with cold water (50 mL), and dried in vacuo to afford 18.2 g (95%) of methyl 1-(4-fluorobenzyl)-3-((3-oxopiperazin-1-yl)methyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxylate. LC-MS (Eclipse XDB-C8, 0.8 mL/min, gradient 80:20 to 5:95H2O (+0.1% HOAc):CH3CN—5 minutes, APCI, +mode): RT—1.41 min, m/e=397.20 (M+H+, base). 1H NMR (300 MHz, DMSO-D6) d ppm 2.55 (t, 2H) 2.92 (s, 2H) 3.11 (s, 2H) 3.74 (s, 2H) 3.84 (s, 3H) 5.56 (s, 2H) 7.16 (t, J=8.85 Hz, 2H) 7.34 (dd, J=8.19, 5.75 Hz, 2H) 7.71 (s, 1H) 7.81 (s, 1H) 8.41 (s, 1H) 8.93 (s, 1H).

1. customThe mixture, under nitrogen, was placed in an oil bath
2. customThe volatiles were removed in vacuo (ca. 2 torr, at 60° C.)
3. customto give a yellow residue
4. customWhite solid precipitated out
5. customthe mixture was sonicated for 30 min
6. temperaturecooled to 10° C
7. filtrationThe solid was filtered
8. washwashed with cold water (50 mL)
9. customdried in vacuo