2-amino-3,5-pyridinedicarbonitrile -Drug Synthesis Database

【结构式】

【分子编号】31544

【品名】2-amino-3,5-pyridinedicarbonitrile

【CA登记号】

【分子式】C₇H₄N₄

【分子量】144.13572

【元素组成】C 58.33% H 2.8% N 38.87%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(I)

The title compound has been prepared by two synthetic procedures. Condensation of 2-aminopyridine-3,5-dicarbonitrile (I) with guanidine (II) in refluxing EtOH produced the pyridopyrimidine (III). Subsequent reductive condensation of (III) with 3,4,5-trimethoxyaniline (IV) by hydrogenation over Raney Nickel provided the (arylamino)methyl derivative (V). Final reductive alkylation of (V) by means of formaldehyde and sodium cyanoborohydride then gave the target methylated amine.

参考文献中间体

合成目标

【1】 Gangjee, A. (Duquesne University); Derivs. of pyrido [2,3-d] and [3,2-d] pyrimidine and methods of using these derivs.. US 5508281 .

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)	31544	2-amino-3,5-pyridinedicarbonitrile		C₇H₄N₄	详情	详情
(II)	14790	Guanidine	113-00-8	CH₅N₃	详情	详情
(III)	14269	2,4-Diaminopyrido[2,3-d]pyrimidine-6-carbonitrile		C₈H₆N₆	详情	详情
(IV)	31545	3,4,5-trimethoxyaniline; 3,4,5-trimethoxyphenylamine；3,4,5-Trimethoxybenzenamine；[3,4,5-Tris(methyloxy)phenyl]amine	24313-88-0	C₉H₁₃NO₃	详情	详情
(V)	31546	2-amino-6-[(3,4,5-trimethoxyanilino)methyl]pyrido[2,3-d]pyrimidin-4-ylamine; 6-[(3,4,5-trimethoxyanilino)methyl]pyrido[2,3-d]pyrimidine-2,4-diamine		C₁₇H₂₀N₆O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

Pyridine (III) was prepared by condensation of malononitrile (I) with triethyl orthoformate (II) in refluxing pyridine, followed by treatment with concentrated HCl. Dechlorination of (III) was effected by hydrogenolysis in the presence of Pd on BaCO3. The dechlorinated pyridine dinitrile (IV) was cyclized with guanidine (V), yielding the pyridopyrimidine (VI). Reduction of the nitrile function of (VI) to aldehyde (VII) was carried out using formic acid and Raney-Ni. This was further reduced to alcohol (VIII) with NaBH4. Bromination of the alcohol (VIII) by means of HBr resulted in bromide (IX). Nucleophilic displacement of the bromide group of (IX) with the sodium salt of 1-naphthalenethiol (X) afforded the target sulfide.

参考文献中间体

合成目标

【1】 Gangjee, A.; et al.; Synthesis of 2,4-diamino-6-(thioarylmethyl)pyrido [2,3-d]pyrimidines as dihydrofolate reductase inhibitors. Bioorg Med Chem 2001, 9, 11, 2929.

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)	12061	Malononitrile	109-77-3	C₃H₂N₂	详情	详情
(II)	21304	Triethyl orthoformate; 1-(Diethoxymethoxy)ethane; Diethoxymethyl ethyl ether	122-51-0	C₇H₁₆O₃	详情	详情
(III)	50364	2-amino-6-chloro-3,5-pyridinedicarbonitrile		C₇H₃ClN₄	详情	详情
(IV)	31544	2-amino-3,5-pyridinedicarbonitrile		C₇H₄N₄	详情	详情
(V)	14790	Guanidine	113-00-8	CH₅N₃	详情	详情
(VI)	14269	2,4-Diaminopyrido[2,3-d]pyrimidine-6-carbonitrile		C₈H₆N₆	详情	详情
(VII)	14270	2,4-Diaminopyrido[2,3-d]pyrimidine-6-carbaldehyde		C₈H₇N₅O	详情	详情
(VIII)	50365	(2,4-diaminopyrido[2,3-d]pyrimidin-6-yl)methanol		C₈H₉N₅O	详情	详情
(IX)	50366	2-amino-6-(bromomethyl)pyrido[2,3-d]pyrimidin-4-ylamine; 6-(bromomethyl)pyrido[2,3-d]pyrimidine-2,4-diamine		C₈H₈BrN₅	详情	详情
(X)	50367	1-Naphthalenethiol	529-36-2	C₁₀H₈S	详情	详情

Extended Information