Sodium Carbonate → HCID 118436056, compound

Participants

Reaction Conditions

Reaction Steps

Two separate reaction vessels containing a yellow mixture of (3S)-3-[4-chloro-2-(morpholin-4-yl)-5,6-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-3-methylpyrrolidine-1-carboxylate (prepared from 2-[4,6-dichloro-2-(morpholin-4-yl)pyrimidin-5-yl]ethanol (Preparation 1) and tert-butyl(3S)-3-amino-3-methylpyrrolidine-1-carboxylate (Preparation 4)) (3500 mg, 8.256 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine (2.37 g, 10.7 mmol) and Na2CO3 (2630 mg, 24.8 mmol) in 1,4-dioxane (90 mL) and water (30 mL), were prepared. To each reaction mixture was added Pd(dppf)Cl2-DCM (362 mg, 0.495 mmol) in one portion at 15° C. under nitrogen atmosphere, and the reaction mixtures were heated at 120° C. for 16 h. The reaction mixtures were combined and concentrated to give 16 g of a black gum. The material was purified by silica gel column chromatography eluting with a gradient of 30-75% EtOAc in petroleum ether, followed by a gradient of 0-1% MeOH in EtOAc to give the title compound (7.0 g, 87%) as a yellow solid. 1H NMR (400 MHz, 80° C., DMSO-d6) δ 8.73 (s, 2 H), 6.61 (br s, 2 H), 3.80-3.63 (m, 11 H), 3.54 (q, J=8.7 Hz, 1 H), 3.42-3.35 (m, 1 H), 3.33-3.25 (m, 1 H), 3.09 (t, J=8.2 Hz, 2 H), 2.44-2.35 (m, 1 H), 2.07-2.00 (m, 1 H), 1.42 (s, 9 H), 1.32 (s, 3 H). m/z (APCI+) for C24H34N8O3 483.2 [M+H]+.

Provenance & Evidence