Yield:-

Reaction Conditions:

with hydrogenchloride in methanol;dichloromethane;

Steps:

2A

144 l-r2-(lH-Indazol-4-yl)-4-moφholin-4-yl-thienor3,2-d]pyrimidin-6-ylmethyl1- piperidine-3-carboxylic acid methylamide.Via l-(2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)- piperidine-3-carboxylic acid methylamide, prepared from piperidine-3-carboxylic acid methylamide. Amine preparation: To a solution of l-(tert-butoxycarbonyl)-3-piperidine- carboxylic acid (0.50g) in DMF (3mL) was added l,l'-carbonyldiimidazole (0.7Og).The reaction mixture was stirred for 4 h and then triethylamine (0.6OmL) followed by methylamine hydrochloride (0.29g) was added. After stirring for 24 h the reaction mixture was then diluted with ethyl acetate, washed with water, brine, dried (MgSO₄) and the solvent removed in vacuo. The residue was purified by flash chromatography EPO to yield 3-methylcarbamoyl-piperidine-l -carboxylic acid tert-butyl ester (0.4Ig). Treatment of this compound with HCl in DCM/MeOH yielded the desired amine, which was isolated as the hydrochloride salt.¹H NMR (400MHz, CDCl₃) 1.58-1.94 (4H, m), 2.50 (2H, m), 2.65 (2H, m), 2.84 (3H, d), 2.80 (IH, m), 3.85 (2H, m), 3.92 (4H, m), 4.10 (4H, m), 7.00 (IH, br s), 7.40 (IH, s), 7.50 (IH, t, J=UUz), 7.60 (IH, d, J=8.2Hz), 8.29 (IH, d, /=7. IHz), 9.03 (IH, s), 10.10 (IH, br s); MS (ESf) 492 (MH⁺).

References:

WO2006/46031,2006,A1 Location in patent:Page/Page column 73-74