Triethyl phosphite → HCID 86662603, compound

Participants

Reaction Steps

Added 5-(1-bromoethyl)-4-[(3-chloro-2-methylphenyl)methyl]-2-(4-morpholinyl)[1,3]thiazolo[4,5-d]pyrimidin-7(4H)-one (179 mg, 0.370 mmol) and triethyl phosphite (4 mL, 22.87 mmol) to a 20 mL screw capped vial and stirred overnight (14 hours) at room temperature. The next morning, starting material was still present, so the contents were transferred to a 25 mL round bottom flask and the contents were heated to 155° C. for 2 hours, whereupon LC/MS showed that the bromo starting material was consumed and a molecular ion corresponding to the desired product was present along with an impurity (believed to be the des-bromo compound by LC/MS). The yellow solution was distilled to remove the unreacted triethyl phosphite, then the residue was purified by column chromatography on silica gel eluted with 0-10% of a (2N solution of NH3 in methanol)/chloroform. The fractions containing product by TLC were combined, then concentrated to provide diethyl {1-[4-[(3-chloro-2-methylphenyl)methyl]-2-(4-morpholinyl)-7-oxo-4,7-dihydro[1,3]thiazolo[4,5-d]pyrimidin-5-yl]ethyl}phosphonate (51 mg, 0.094 mmol, 25.5% yield) as a light tan solid. LC/MS m/z MH+=541 (theoretical), found=541.1, 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.23-1.36 (m, 6H) 1.47 (dd, J=17.31, 6.95 Hz, 3H) 2.46 (s, 3H) 3.02-3.18 (m, 1H) 3.49-3.60 (m, 4H) 3.71-3.82 (m, 4H) 4.00-4.27 (m, 4H) 5.67 (d, J=−17.68 Hz, 1H) 5.90 (d, J=17.68 Hz, 1H) 6.41 (d, J=7.58 Hz, 1H) 7.05 (t, J=7.83 Hz, 1H) 7.32 (d, J=7.58 Hz, 1H)

Provenance & Evidence