Ethyl 2-(4-(hydroxymethyl)piperidin-1-yl)pyrimidine-5-carboxylate

Off-white solid

Stage 1 - Coupling; Piperidin-4yl-methanol (2.48g, 21.55mmol) was stirred in 1 :1 DMF/MeCN (2OmL) with KA solution of 2-(methylsulfonyl)- 5-pyrimidinecarboxylic acid, ethyl ester (0.094 mol)in acetonitrile (40ml) was added at 10°C to a suspension of 4-piperidinemethanol(0.086 mol) and potassium carbonate (0.172 mol) in acetonitrile (200ml) under N2flow. The mixture was brought to room temperature, then stirred for 4 hours, pouredout into water and extracted with EtOAc. The organic layer was separated, dried(MgSO4), filtered, and the solvent was evaporated. The residue (23 g) was crystallizedfrom acetonitrile/diethyl ether. The precipitate was filtered off and dried, yielding 7.8g(34percent) of intermediate 8. The mother layer was evaporated. The residue (17g) waspurified by column chromatography over silica gel (20-45um) (eluent:DCM/MeOH/NHa) Preparation of intermediate 3 A solution of 2-(methylsulfonyl)-5-pyrimidinecarboxylic acid ethyl ester (0.094 mol) in acetonitrile (40ml) was added at 1Oa) Preparation of intermediate 7 A solution of 2-(methylsulfonyl)-5-pyrimidinecarboxylic acid, ethyl ester (0.094 mol) in acetonitrile (40ml) was added at 10Step 18a: Ethyl 2-(4-hydroxypiperidin-l-yl)pyrimidine-5-carboxylate (Compound 0701)A mixture of compound 0605 (900 mg, 4.84 mmol), piperidin-4-ylmethanol (0.56 g, 4.86 mmol) and potassium carbonate (330 mg, 2.39 mmol) in DMF (2 mL) was stirred at ambient temperature for 2.5 h. The DMF was removed under reduced pressure and the residue was poured into brine, filtered to obtain the product 0701 (1.20 g, 95 percent) as a yellow solid: LCMS: 266 [M+ 1]

Molecular Weight:265.31
XLogP3:0.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:5
Exact Mass:265.14264148
Monoisotopic Mass:265.14264148
Topological Polar Surface Area:75.6
Heavy Atom Count:19
Complexity:285
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes