1,8-Diazabicyclo(5.4.0)undec-7-ene → (4-Chloro-phenyl)-{4-[(3S,4S)-4-hydroxy-1-(6-methoxy-quinazolin-4-yl)-pyrrolidin-3-yl]-piperazin-1-yl}-methanone

Participants

Reaction Steps

To 0.326 mmoles of (4-Chloro-phenyl)-[4-(4-hydroxy-pyrrolidin-3-yl)-piperazin-1-yl]-methanone (synthesis described above in Example 5), add 1.6 mL acetonitrile and 1.6 mmoles of DBU. The stirred solution was cooled in ice and then 0.358 mmoles of 4-chloro-6-methoxy-quinazoline was added and the reaction mixture was allowed to stir for a period of 2.5 hours. To 0.326 mmoles of (4-Chloro-phenyl)-[4-(4-hydroxy-pyrrolidin-3-yl)-piperazin-1-yl]-methanone, add 1.6 mL acetonitrile and 1.63 mmoles of DBU. The stirred solution was cooled in ice and then 0.358 mmoles of 4-chloro-6-methoxy-2-methyl-quinazoline (from Step 2 above) was added and the reaction mixture was allowed to stir for a period of 2.5 hours. For the reaction workup, the reaction mixture was diluted with methanol and concentrated on the rotavap. To the concentrate about 30 mL of water was added and was extracted with 40 mL EtOAc. The organic layer was separated and washed with 30 mL of 1M aq K2CO3 solution, and brine, dried over MgSO4 and excess solvent was removed on rotavap to yield a crude oil. This was diluted with about 2 mL EtOAc and about 8 mL ether was added and the white solid obtained was filtered off and vacuum dried to give the title compound in 50% yield. LC-MS: m/z=468 (M++1).

Provenance & Evidence