Reaction #44175

Reaction equation

1,1-dimethylethyl 2-{[(3-{2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}phenyl)amino]methyl}-1-pyrrolidinecarboxylate

hydrogen chloride

triphosgene

diisopropylamine

→

title compound

(R)-2-(3-{2-[4-(2-Methyl-5-quinolinyl)-1-piperazinyl]ethyl}phenyl)hexahydro-3H-pyrrolo[1,2-c]imidazol-3-one

Solvents

methanol

ether

Conditions

Workup

1. 1
   Concentrationthen concentrated under vacuum
2. 2
   Washeluted with methanol
3. 3
   ConcentrationThe combined basic fractions were concentrated under vacuum
4. 4
   workup.DISSOLUTIONThe residue, (10 mg) was then dissolved in DCM (1 mL)
5. 5
   workup.STIRRINGThe mixture was stirred for 1 h
6. 6
   Concentrationthen concentrated under vacuum
7. 7
   Otherpurified by preparative mass-directed hplc

Procedure

A solution of (R)-(1,1-dimethylethyl 2-{[(3-{2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}phenyl)amino]methyl}-1-pyrrolidinecarboxylate in methanol was treated with a solution of hydrogen chloride in ether (1M). The resulting mixture was stirred 30 minutes then concentrated under vacuum and then loaded onto an ion-exchange cartridge (SCX-2) and eluted with methanol followed by ammonia in methanol (1 M). The combined basic fractions were concentrated under vacuum. The residue, (10 mg) was then dissolved in DCM (1 mL) and treated with triphosgene (23 mg, 0.3 eq.), diisopropylamine (4 uL, 3 eq.). The mixture was stirred for 1 h then concentrated under vacuum and purified by preparative mass-directed hplc to afford the title compound (3.1 mg).

Source