Sodium Carbonate → HCID 58465932, compound

Participants

Reaction Conditions

Reaction Steps

A glass microwave reaction vessel was charged with 7-bromo-3-chloro-6′-cyclohexyl-2′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,3′-[1,4]oxazin]-5′-amine (0.075 g, 0.162 mmol), 2 M aqueous sodium carbonate (0.8 mL, 1.600 mmol), and dioxane (1.6 mL). The vessel was capped and the solution was degassed by bubbling nitrogen gas through the solution for 10 minutes. Next, Pd(PPh3)4 (7.49 mg, 6.48 μmol) and (2-fluoropyridin-3-yl)boronic acid (0.027 g, 0.194 mmol) were added and the vessel was sealed. The reaction mixture was stirred and heated in a Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 120° C. for 20 minutes. The reaction was poured into water and the mixture was extracted with EtOAc. The combined organic extracts were washed with water, saturated aqueous sodium chloride, and dried over sodium sulfate. The solution was filtered and concentrated in vacuo to give the crude material. The crude material was purified by silica gel chromatography by eluting with 1:20 MeOH in DCM, to provide the product as a racemic mixture of diastereomers. The diastereomers were seperated by reverse-phase preparative HPLC using a Phenomenex Gemini column, 10 micron, C18, 100 Å, 150×30 mm, 0.1% TFA in CH3CN/H2O, gradient 10% to 70% over 20 min to provide racemic (3′R, 6′S)-3-chloro-6′-cyclohexyl-7-(2-fluoropyridin-3-yl)-2′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,3′-[1,4]oxazin]-5′-amine and racemic (3′S, 6′S)-3-chloro-6′-cyclohexyl-7-(2-fluoropyridin-3-yl)-2′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,3′-[1,4]oxazin]-5′-amine each as a white solid after isolating the free base by partitoning between DCM and 1 N NaOH. [M+H]+=479.1 for each racemic diastereomer pair.

Provenance & Evidence