tert-Butyl methylcarbamate → tert-butyl N-methyl-N-[6-(2-morpholin-4-yl-4-oxopyrido[1,2-a]pyrimidin-9-yl)dibenzothiophen-2-yl]carbamate

Participants

Reaction Conditions

Reaction Steps

tert-butyl methylcarbamate (3.04 g, 23.15 mmol) dissolved in dioxane (5ml) was added in one portion to 6-(2-morpholino-4-oxo-4H-pyrido[1,2-a]pyrimidin-9-yl)dibenzo[b,d]thiophen-2-yl trifluoromethanesulfonate (6.50g, 11.58 mmol) , TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (0.265 g, 0.29 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.335 g, 0.58 mmol) and cesium carbonate (15.09 g, 46.30 mmol) in degassed dioxane (18 mL), under nitrogen. The reaction flask was evacuated and blanketed with nitrogen 4X. __The resulting suspension was stirred at 110 °C for 3 __ hours with complete reaction observed by LCMS. After cooling, the mixture was partitioned between EtOAc (500mL) and water (250ml). The organics were separated and dried (MgSO4) and evaporated to give the crude product which was combined with the crude product from EN02472-66. The crude product was purified by flash silica chromatography, elution gradient 0 to 5% MeOH in DCM. Pure fractions were evaporated to dryness to afford tert-butyl methyl(6-(2-morpholino-4-oxo-4H-pyrido[1,2-a]pyrimidin-9-yl)dibenzo[b,d]thiophen-2-yl)carbamate (5.61 g, 89 %) as a yellow solid. 1H NMR (400 MHz, CDCl3, 22°C) d 1.48 (9H, s), 3.34 - 3.39 (7H, m), 3.54 - 3.59 (4H, m), 5.63 (1H, s), 6.99 - 7.05 (1H, m), 7.34 (1H, dd), 7.56 (2H, m), 7.72 (1H, d), 7.86 (1H, dt), 8.04 (1H, s), 8.16 (1H, dt), 9.04 (1H, m). m/z (ES+) (M+H)+ = 543; HPLC tR= 2.89 min.

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