4-Amino-6-chloropyrimidine → 1-(6-Aminopyrimidin-4-yl)azetidin-3-ol

Participants

Reaction Steps

A solution of 3-azetidinol hydrochloride (454 mg, 4.1 mmol) in MeOH and water was loaded onto an Isolute® SCX-2 cartridge that was washed with MeOH and the product eluted with 2M ammonia in MeOH. The relevant fractions were concentrated to dryness under reduced pressure. The resultant residue was then added to a solution of 6-chloro-pyrimidin-4-ylamine (151 mg, 1.16 mmol) in IMS (10 mL) under argon and heated under reflux for 18 hours. The reaction mixture was cooled and then loaded onto an Isolute® SCX-2 column. The column was then washed with MeOH and eluted with 2 M ammonia in MeOH. The relevant fractions were concentrated to dryness under reduced pressure and the resulting residue was purified by flash chromatography (NH2 cartridge, 0-5% MeOH in DCM) to give the desired compound as a white solid (163 mg, 85% yield). 1H NMR (400 MHz, DMSO-d6): δ 7.90 (d, J=1.0 Hz, 1H), 6.18 (s, 2H), 5.65 (d, J=6.5 Hz, 1H), 5.21 (d, J=1.1 Hz, 1H), 4.54-4.53 (m, 1H), 4.07 (dd, J=8.7, 6.7 Hz, 2H), 3.59 (dd, J=8.8, 4.6 Hz, 2H).

Provenance & Evidence