2-((6-Chloro-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)methyl)benzonitrile -Drug Synthesis Database

【结构式】

【分子编号】65544

【品名】2-((6-Chloro-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)methyl)benzonitrile

【CA登记号】865758-95-8

【分子式】C₁₂H₈ClN₃O₂

【分子量】261.66724

【元素组成】C 55.08% H 3.08% Cl 13.55% N 16.06% O 12.23%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(III)

6-Chlorouracil (I) is alkylated with 2-(bromomethyl)benzonitrile (II) in the presence of NaH and LiBr in DMF/DMSO to produce the N-benzyluracil derivative (III), which is further alkylated with iodomethane and NaH in DMF/THF to yield the 1,3-disubstituted uracil (IV) (1-3). Intermediate (IV) is alternatively obtained by alkylation of 6-chloro-3-methyluracil (V) with 2-(bromomethyl)benzonitrile (II) by means of diisopropylethylamine in hot NMP (3). Subsequent displacement of chlorouracil (IV) with 3(R)-aminopiperidine dihydrochloride (VI) in the presence of either NaHCO3 in hot methanol or K2CO3 in aqueous isopropanol provides alogliptin (1-3), which is isolated as the corresponding benzoate salt by treatment with benzoic acid in ethanol (3). Scheme 1.

参考文献中间体

合成目标

【1】 Feng, J., Gwaltney, S.L., Stafford, J.A. et al. (Takeda San Diego, Inc.). Dipeptidyl peptidase inhibitors. EP 1586571, JP 2005263780, US2005261271, WO 2005095381.
【2】 Feng, J., Zhang, Z., Wallace, M.B. et al. Discovery of alogliptin: A potent, selective, bioavailable, and efficacious inhibitor of dipeptidyl peptidase IV. J Med Chem 2007, 50(10): 2297-300.
【3】 Feng, J., Gwaltney, S.L., Stafford, J.A. et al. (Takeda Pharmaceutical Co., Ltd.). WO 2007035629.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	65543	6-Chloro-2,4-Pyrimidinediol	107577-09-3	C₄H₃ClN₂O₂	详情	详情
(II)	33303	2-(bromomethyl)benzonitrile	22115-41-9	C₈H₆BrN	详情	详情
(III)	65544	2-((6-Chloro-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)methyl)benzonitrile	865758-95-8	C₁₂H₈ClN₃O₂	详情	详情
(IV)	65545	2-((6-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)methyl)benzonitrile		C₁₃H₁₀N₃O₂	详情	详情
(V)	65546	6-Chloro-3-methyluracil; 3-Methyl-6-chlorouracil	4318-56-3	C₅H₅ClN₂O₂	详情	详情
(VI)	65547	(R)-3-Aminopiperidine dihydrochloride		C₅H₁₂N₂.2HCl	详情	详情

Extended Information