p-Toluenesulfonic acid monohydrate → 3-methoxy-4-[[6-(1-methoxypropan-2-yl)-2-methyl-3-oxo-2,6,8,10-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-9-yl]amino]-N-(1-methyl-4-piperidyl)benzamide

Participants

Reaction Conditions

Reaction Steps

10-chloro-2-(1-methoxypropan-2-yl)-6-methyl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one (Intermediate 112 60 mg, 0.21 mmol), 4-amino-3-methoxy-N-(1-methyl-4-piperidyl)benzamide (WO06/018220; 56 mg, 0.21 mmol), and p-toluenesulphonic acid monohydrate (100 mg, 0.53 mmol) were combined in 4-Methyl-2-pentanol (2 mL) and heated at 100° C. for 16 hrs. The reaction mixture was cooled to room temperature and dissolved in Methanol. The resultant solution was added to a 5 g SCX-3 column pre wet with MeOH (2 column volumes). Flushed with MeOH (2 column volumes) and crude product eluted with 2M ammonia in MeOH and solvents evaporated. The resultant residue was dissolved in DCM and purified on silica eluting with a gradient of 5-15% MeOH/DCM. Product containing fractions were combined and evaporated to a yellow gum which was purified by base modified reverse phase HPLC to give the title compound as a beige solid. (35 mg, 32%)

Provenance & Evidence