Trifluoroacetic acid → 3-Amino-4-chloro-5-(3-fluoro-3-azetidinyl)benzonitrile

Reaction equation

C(OC([N:8](CC1C=CC(OC)=CC=1)[C:9]1[C:10]([Cl:29])=[C:11]([C:17]2([F:28])[CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18]2)[CH:12]=[C:13]([C:15]#[N:16])[CH:14]=1)=O)(C)(C)C.C1(OC)C=CC=CC=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:8][C:9]1[CH:14]=[C:13]([CH:12]=[C:11]([C:17]2([F:28])[CH2:18][NH:19][CH2:20]2)[C:10]=1[Cl:29])[C:15]#[N:16]

Participants

Procedure

To a solution of tert-butyl 3-(3-((tert-butoxycarbonyl)(4-methoxybenzyl)amino)-2-chloro-5-cyanophenyl)-3-fluoroazetidine-1-carboxylate, (Example 658B) (321 mg) in DCM (15 ml) was added anisole (0.5 mL, 4.52 mmol), followed by TFA (7 ml). The resulting mixture was stirred at room temperature overnight. Solvent was removed. The residue was taken in MeOH and applied onto a cartridge of Phenomenex Strata-X-C 33 um cation mixed-mode polymer. This was washed with methanol and the product was eluted with 2 N solution of ammonia in methanol. Removal of the solvents left 3-amino-4-chloro-5-(3-fluoroazetidin-3-yl)benzonitrile (127 mg) as a solid.