5-Methoxy[1,3]thiazolo[5,4-b]pyridin-2-amine → (R)-3-cyclopentyl-N-(5-methoxy-thiazolo[5,4-b]pyridin-2-yl)-2-phenyl-propionamide

Participants

Reaction Conditions

Reaction Steps

The title D compound, (R)-3-cyclopentyl-2-phenyl-propionic acid (1.66 g, 7.605 mmol) is dissolved in thionyl chloride (15 mL) and heated at 50° C. for 1.5 h. The reaction is then cooled to RT and concentrated to afford a yellow oil. This is dissolved in anhydrous THF (10 mL) and added dropwise to a solution of the title E compound, 5-methoxy-thiazolo[5,4-b]pyridin-2-ylamine (1.38 g, 7.605 mmol) in anhydrous pyridine (10 mL) at 0° C. The reaction is allowed to stir and warm to RT. After 2 h, the reaction is concentrated to remove the THF and most of the pyridine. The resulting brown oil is dissolved in ethyl acetate (250 mL)/1 N HCl (250 mL) and extracted further with ethyl acetate. The combined organic layer is dried over anhydrous sodium sulfate, filtered, and concentrated to afford the crude product as a brown oil. This is chromatographed over silica eluting with 5→60% ethyl acetate in hexanes to afford (R)-3-cyclopentyl-N-(5-methoxy-thiazolo[5,4-b]pyridin-2-yl)-2-phenyl-propionamide as a yellow foam: 1H NMR (400 MHz, DMSO-D6) 1.1 (m, 2 H) 1.4 (dd, J=7.2, 4.7 Hz, 2 H) 1.6 (m, 3 H) 1.7 (m, 3 H) 2.1 (m, 1 H) 3.9 (m, 4 H) 6.9 (d, J=8.8 Hz, 1 H) 7.3 (m, 1 H) 7.4 (m, 4 H) 8.0 (d, J=8.6 Hz, 1 H) 12.5 (s, 1 H); LC/MS 382.1 (M+1), 380.2 (M−1).

Provenance & Evidence