2,2-dimethyl-N-[6-methyl-4-oxo-5-[(4-pyridinylsulfanyl)methyl]-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-2-yl]propanamide -Drug Synthesis Database

【结构式】

【分子编号】27937

【品名】2,2-dimethyl-N-[6-methyl-4-oxo-5-[(4-pyridinylsulfanyl)methyl]-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-2-yl]propanamide

【CA登记号】

【分子式】C₁₈H₂₁N₅O₂S

【分子量】371.46324

【元素组成】C 58.2% H 5.7% N 18.85% O 8.61% S 8.63%

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：(VIII)

Condensation of 2,6-diamino-4-hydroxypyrimidine (I) with chloroacetone (II) produced a mixture of pyrrolopyrimidine (III) and furopyrimidine (IV). After treatment of this mixture with pivalic anhydride, the insoluble pivaloyl amide of pyrrolopyrimidine (V) was separated from the soluble dipivaloyl furopyrimidine with boiling EtOAc. Subsequent Mannich reaction of (V) with dimethylamine and formaldehyde afforded the (dimethylamino)methyl derivative (VI). The dimethylamino group of (VI) was then displaced with 4-mercaptopyridine (VII) to give thioether (VIII). Finally, the pivaloyl amide group of (VIII) was hydrolyzed with NaOH to yield the target compound.

参考文献中间体

合成目标

【1】 Gangjee, A.; et al.; 2-Amino-4-oxo-5-substituted-pyrrolo[2,3-d.]pyrimidines as nonclassical antifolate inhibitors of thymidylate synthase. J Med Chem 1996, 39, 23, 4563-4568.
【2】 Gangjee, A.; et al.; Synthesis of classical and a nonclassical 2-amino-4-oxo-6-methyl-5-substituted Pyrrolo[2,3-d]pyrimidine antifolate inhibitors of thymidylate synthase1. J Med Chem 1999, 42, 12, 2272.

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)	14227	N-Hydroxy-2-phenyl-4,5-dihydro-1,3-oxazole-4-carboxamide		C₁₀H₁₀N₂O₃	详情	详情
(II)	15288	1-Chloroacetone; Chloroacetone	78-95-5	C₃H₅ClO	详情	详情
(III)	27932	2-amino-6-methyl-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one		C₇H₈N₄O	详情	详情
(IV)	27933	5-methylfuro[2,3-d]pyrimidine-2,4-diamine		C₇H₈N₄O	详情	详情
(V)	27934	2,2-dimethyl-N-(6-methyl-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-2-yl)propanamide		C₁₂H₁₆N₄O₂	详情	详情
(VI)	27935	N-[5-[(dimethylamino)methyl]-6-methyl-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-2-yl]-2,2-dimethylpropanamide		C₁₅H₂₃N₅O₂	详情	详情
(VII)	27936	4-Mercaptopyridine; 4-pyridinethiol	4556-23-4	C₅H₅NS	详情	详情
(VIII)	27937	2,2-dimethyl-N-[6-methyl-4-oxo-5-[(4-pyridinylsulfanyl)methyl]-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-2-yl]propanamide		C₁₈H₂₁N₅O₂S	详情	详情

Extended Information