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0 °C

Aqueous formaldehyde (37.4% or 13.5 M, 0.134 mL, 1.80 mmol) is added to a stirred solution of 2-[5-chloro-2-(2-piperidin-4-ylethylamino)-pyrimidin-4-yl]-benzo[b]thiophene-4-carboxylic acid amide (150 mg, 0.361 mmol) in CH3OH (15 mL) and dichloromethane (15 mL) at room temperature to form a light suspension. The mixture is allowed to stir for 90 minutes. The mixture is cooled to 0° C. before it is treated with powdered sodium borohydride (68.1 mg, 1.80 mmol). The mixture is stirred at 0° C. for 1 hour, then allowed to slowly warm up to room temperature to form a clear solution. After concentration, the crude product is subject to chromatographic purification on silica gel, eluting with 2 M NH3/CH3OH in dichloromethane 4-12%, to give the desired methylated product as a yellowish solid. The free base is dissolved in CH3OH (20 mL) and dichloromethane (20 mL) then treated with 12 N HCl (0.30 mL) to form a yellow solution. After concentration and vacuum drying at 60° C., the title compound is obtained as a yellow solid (174 mg, 95% yield). ES+(m/z) 430 (35Cl) and 432 (37Cl) [M(free base)+H].

1. customto form a light suspension
2. stirringThe mixture is stirred at 0° C. for 1 hour
3. temperatureto slowly warm up to room temperature
4. customto form a clear solution
5. concentrationAfter concentration
6. customthe crude product is subject to chromatographic purification on silica gel
7. washeluting with 2 M NH3/CH3OH in dichloromethane 4-12%
8. customto give the
9. customto form a yellow solution
10. concentrationAfter concentration and vacuum
11. customdrying at 60° C.