2,4-diamino-5-pyrimidinecarbaldehyde -Drug Synthesis Database

【结构式】

【分子编号】26525

【品名】2,4-diamino-5-pyrimidinecarbaldehyde

【CA登记号】

【分子式】C₅H₆N₄O

【分子量】138.129

【元素组成】C 43.48% H 4.38% N 40.56% O 11.58%

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)

Condensation of pyrimidine carboxaldehyde (I) with 3,5-dimethoxy-phenylacetonitrile (II) using NaH in 2-ethoxyethanol provided the pyridopyrimidine (III). Then, regioselective condensation of (III) with tert-butyl isocyanate at the 7-amino group in the presence of NaH in DMF furnished the corresponding urea.

参考文献中间体

合成目标

【1】 Connolly, C.J.C.; Schroeder, M.C.; Hamby, J.M.; et al.; Structure-activity relationships for a novel series of pyrido[2,3-d]pyrimidine tyrosine kinase inhibitors. J Med Chem 1997, 40, 15, 2296.
【2】 Hamby, J.M.; Connolly, C.J.C.; Schroeder, M.C.; et al.; Discovery and structure-activity studies of a novel series of pyrido[2,3-d]pyrimidine tyrosine kinase inhibitors. Bioorg Med Chem Lett 1997, 7, 18, 2415.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	16976	tert-butylisocyanate; tert-butyl isocyanate; 2-isocyanato-2-methylpropane	1609-86-5	C₅H₉NO	详情	详情
(I)	26525	2,4-diamino-5-pyrimidinecarbaldehyde		C₅H₆N₄O	详情	详情
(II)	26526	2-(3,5-dimethoxyphenyl)acetonitrile	13388-75-5	C₁₀H₁₁NO₂	详情	详情
(III)	26527	2-amino-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-ylamine		C₁₅H₁₅N₅O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

Condensation of guanidine nitrate (I) with (ethoxymethylene)malononitrile (II) in the presence of NaOEt yields 2,4-diaminopyrimidine-5-carbonitrile (III). Reduction of nitrile (III) by means of Raney nickel in formic acid leads to aldehyde (IV), which is further reduced to alcohol (V) by means of NaBH4. Treatment of alcohol (V) with HBr in AcOH gives the bromide (VI), which is condensed with pyridine in DMF to form the crystalline pyridinium salt (VII). Finally, displacement of compound (VII) with the tetrahydroisoquinoline (VIII), followed by resolution by chiral HPLC, furnishes the title compound.

参考文献中间体

合成目标

【1】 Gerber, P.; Wyss, P.C.; Hartman, P.G.; Hubschwerlen, C.; Locher, H.; Marty, H.-P.; Stahl, M.; Novel dihydrofolate reductase inhibitors. Structure-based versus diversity-based library design and high-throughput synthesis and screening. J Med Chem 2003, 46, 12, 2304.

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)	14790	Guanidine	113-00-8	CH₅N₃	详情	详情
(II)	13017	Ethoxymethylenemalononitrile; 2-(Ethoxymethylene)malononitrile	123-06-8	C₆H₆N₂O	详情	详情
(III)	64871	2,4-diamino-5-pyrimidinecarbonitrile		C₅H₅N₅	详情	详情
(IV)	26525	2,4-diamino-5-pyrimidinecarbaldehyde		C₅H₆N₄O	详情	详情
(V)	64872	(2,4-diamino-5-pyrimidinyl)methanol		C₅H₈N₄O	详情	详情
(VI)	64873	5-(bromomethyl)-2,4-pyrimidinediamine		C₅H₇BrN₄	详情	详情
(VII)	64874	1-[(2,4-diamino-5-pyrimidinyl)methyl]pyridinium bromide		C₁₀H₁₂BrN₅	详情	详情
(VIII)	64875	methyl 9-methyl-6,7,8,9-tetrahydro[1,3]dioxolo[4,5-h]isoquinolin-4-yl ether; 9-methyl-4-(methyloxy)-6,7,8,9-tetrahydro[1,3]dioxolo[4,5-h]isoquinoline		C₁₂H₁₅NO₃	详情	详情

Extended Information