Water → (R)-tert-butyl 4-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-5,6-dihydropyridine-1(2H)-carboxylate

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Reaction Conditions

Reaction Steps

A solution of Na2CO3 (0.36 mL, 2M) was added to a solution of (R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine (101 mg, 0.60 mmol), 3,6-dihydro-2H-pyridine-1-tert-butoxycarbonyl-4-boronic acid, pinacol ester (204 mg, 0.66 mmol) in 1,4-dioxane (1.8 mL). The mixture was sparged with N2 for 2 minutes. The catalyst Pd(PPh3)2Cl2 (21 mg, 0.03 mmol) was added in one portion. The mixture was heated at 110° C. under N2 for 8 hours. Water (20 mL) was added to the mixture and extracted with DCM (3×15 mL). The combined organics were dried (Na2SO4), filtered and concentrated. The crude product was purified by flash chromatography (first with 0-50% EtOAc/hexane, then with 0-4% MeOH/DCM gradient elution) to give (R)-tert-butyl 4-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-5,6-dihydropyridine-1(2H)-carboxylate as an oil (127 mg, 67%). 1H NMR (CDCl3, 500 MHz) δ 8.91 (s, 1H), 6.31 (s, 1H), 3.64-3.55 (m, 1H), 3.10-3.03 (m, 2H), 2.98-2.90 (m, 2H), 2.83-2.78 (m, 1H), 2.42-2.34 (m, 2H), 1.77-1.69 (m, 2H). 1.49 (s, 9H), 1.19 (d, J=7.0 Hz, 3H).

Provenance & Evidence