2-Methylpyrrolidine → 2-chloro-7-(4-fluorophenyl)-4-(2-methylpyrrolidin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine

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 2-Methylpyrrolidine (82 mL, 0.848 mmol). The resulting mixture was stirred at RT for 2 days. The reaction mixture was then concentrated in vacuo. The resulting oil was purified by flash chromatography (Silica, EtOAc/Hexanes) to give two racemic pairs of diasteriomers 2-chloro-7-(4-fluorophenyl)-4-(2-methylpyrrolidin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine. (Hc1, Diastereomer 1, racemic, first to elute) (79.5 mg, 0.240 mmol, 33.9% yield). LC-MS (M+H)+=332.1; 1H NMR (500 MHz, MeOD) δ ppm 7.16 (2 H, d, J=5.49 Hz), 7.04 (2 H, s), 4.42-4.54 (1 H, m), 4.09-4.22 (1 H, m), 3.86-4.00 (1 H, m), 3.71-3.82 (1 H, m), 3.24-3.31 (1 H, m), 3.10-3.22 (1 H, m), 2.54-2.65 (1 H, m), 2.05-2.16 (2 H, m), 1.94-2.05 (2 H, m), 1.69-1.80 (1 H, m), 1.27 (3 H, d, J=6.10 Hz). (Hc2, Diastereomer 2, racemic, second to elute) (89.5 mg, 0.270 mmol, 38% yield). LC-MS (M+H)+=332.1; 1H NMR (500 MHz, MeOD) δ ppm 7.14 (2 H, d, J=5.49 Hz), 6.99-7.08 (2 H, m), 4.42-4.54 (1 H, m), 4.13-4.22 (1 H, m), 3.86-4.00 (1 H, m), 3.71-3.83 (1 H, m), 3.25-3.32 (1 H, m), 3.14-3.25 (1 H, m), 2.52-2.67 (1 H, m), 2.05-2.19 (2 H, m), 1.94-2.05 (2 H, m), 1.68-1.78 (1 H, m), 1.19-1.32 (3 H, m). The relative stereochemistry for Hc1 and Hc2 was not determined

1. concentrationThe reaction mixture was then concentrated in vacuo
2. customThe resulting oil was purified by flash chromatography (Silica, EtOAc/Hexanes)

ORD record

ord-e182d8dcfebf4b888b9624c8373a7bab

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08710061B2