Methanesulfonic Acid → HCID 18932824, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 4-(6-chloro-2,3-dihydro-indol-1-yl)-6-methoxy-quinazolin-7-ol (200 mg, 0.610 mmol; from Example 70) and triphenylphosphine(160 mg, 0.610 mmol) in dry THF (3 mL) under N2(g) was added diethyl-azodicarboxylate (106 μL, 0.671 mmol) dropwise at 0° C. over 10 minutes followed by a solution of 4-(2-hydroxyethyl)-morpholine (81 μL, 0.671 mmol) in dry THF (0.8 mL). The mixture was allowed to warm to 20° C. and stirred 16 hours before quenching with H2O (20μL) and concentrating in vacuo. Flash chromatography of the residue on silica using first 45% acetone/CH2Cl2 followed by 10% MeOH/CH2Cl2 eluted the product as its free-base (180 mg), which was precipitated as its bis(methanesulfonate) salt by addition of 2.0 eq. of methanesulfonic acid to a solution in CH2Cl2. (M.P. 150°-158° C. (dec); LC-MS: 441 (MH+); anal. RP18-HPLC RT: 3.76 min.).

Provenance & Evidence