2,6-Dimethylmorpholine, cis- → (2S,6R)-4-(2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-2,6-dimethylmorpholine

To a solution of 2,4-dichloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine (Preparation H) (200 mg, 0.706 mmol) in MeOH (7064 mL) was added cis-2,6-Dimethylmorpholine (105 mL, 0.848 mmol). The resulting mixture was stirred at RT overnight. An additional 2 equ. of cis-2,6-Dimethylmorpholine was then added and the mixture was again stirred overnight at RT. The reaction mixture was then concentrated in vacuo. The resulting oil was purified by flash chromatography (Silica, EtOAc/Hexanes) to give (2S,6R)-4-(2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-2,6-dimethylmorpholine (223 mg, 0.616 mmol, 87% yield). LC-MS (M+H)+=332.1. 1H NMR (500 MHz, MeOD) δ ppm 7.11-7.24 (2 H, m), 6.99-7.09 (2 H, m), 4.39-4.51 (2 H, m), 4.20 (1 H, s), 3.70 (2 H, td, J=4.12, 2.44 Hz), 3.14-3.25 (1 H, m), 3.03-3.13 (1 H, m), 2.69-2.80 (2 H, m), 2.54-2.68 (1 H, m), 1.95-2.13 (1 H, m), 1.23 (6 H, d, J=6.10 Hz).

1. waitthe mixture was again stirred overnight at RT
2. concentrationThe reaction mixture was then concentrated in vacuo
3. customThe resulting oil was purified by flash chromatography (Silica, EtOAc/Hexanes)

ORD record

ord-03275b50950345e0950d3113aba2424b

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08710061B2