2-amino-4-pyrimidinecarbaldehyde -Drug Synthesis Database

【结构式】

【分子编号】25436

【品名】2-amino-4-pyrimidinecarbaldehyde

【CA登记号】

【分子式】C₅H₅N₃O

【分子量】123.11432

【元素组成】C 48.78% H 4.09% N 34.13% O 13%

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：(X)

In the original procedure, pyruvic aldehyde dimethyl acetal (VI) was condensed with N,N-dimethylformamide dimethyl acetal to give enaminoketone (VII). Subsequent reaction of (VII) with guanidine (VIII) provided 2-aminopyrimidine-4-carboxaldehyde dimethyl acetal (IX), which was hydrolyzed to the corresponding aldehyde (X) with 3 N HCl at 48 C. This was condensed with 4-amino-2,2,6,6-tetramethylpiperidine (XI) to produce imine (XII). Finally, reaction between imine (XII) and tosyl isonitrile (V) in the presence of K2CO3 generated the target imidazole.

参考文献中间体

合成目标

【1】 Adams, J.L.; Gallagher, T.F.; Garigipati, R.S.; Boehm, J.C.; Sisko, J.; Peng, Z.-Q.; Lee, J.C.-L. (SmithKline Beecham plc); Certain 1,4,5-tri-substd. imidazole cpds. useful as cytokine. EP 0809499; JP 1998512555; US 5593992; WO 9621452 .
【2】 Adams, J.L.; Boehm, J.C.; Imidazole cpds., use and process of making. US 5593991 .
【3】 Garigipati, R.S.; Adams, J.L.; Boehm, J.C. (SmithKline Beecham Corp.); Pyridyl imidazole cpds. and compsns.. US 5670527 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(V)	25595	4-Fluoro-alpha-(4-methylphenylsulfonyl)benzyl isocyanide		C₁₅H₁₂FNO₂S	详情	详情
(VI)	25433	1,1-dimethoxyacetone	6342-56-9	C₅H₁₀O₃	详情	详情
(VII)	25434	(E)-4-(dimethylamino)-1,1-dimethoxy-3-buten-2-one		C₈H₁₅NO₃	详情	详情
(VIII)	14790	Guanidine	113-00-8	CH₅N₃	详情	详情
(IX)	25435	4-(dimethoxymethyl)-2-pyrimidinylamine		C₇H₁₁N₃O₂	详情	详情
(X)	25436	2-amino-4-pyrimidinecarbaldehyde		C₅H₅N₃O	详情	详情
(XI)	25596	2,2,6,6-tetramethyl-4-piperidinamine	36768-62-4	C₉H₂₀N₂	详情	详情
(XII)	25597	4-[[(2,2,6,6-tetramethyl-4-piperidinyl)imino]methyl]-2-pyrimidinamine		C₁₄H₂₃N₅	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 pyruvic aldehyde dimethyl acetal (I) with dimethylformamide dimehylacetal provided ketoenamine (II). This was cyclized with guanidine to afford aminopyrimidine (III). Then, hydrolysis of the dimethyl acetal of (III) with 3 M HCl yielded aldehyde (IV). 4-Fluorobenzaldehyde (V) was condensed with thiocresol (VI) and formamide in refluxing toluene to give 4-fluorophenyl-tolylthiomethyl formamide (VII), which was dehydrated to isocyanide (VIII) with POCl3 and Et3N at -30 C. Finally, imine (X), (obtained from pyrimidine aldehyde (IV) and 4-(3-aminopropyl)morpholine (IX)), was condensed with isocyanide (VIII) in the presence of 1,5,7-triazabicyclo[4.4.0]dec-5-ene to furnish the title imidazole.

参考文献中间体

合成目标

【1】 Adams, J.L.; Boehm, J.C.; Kassis, S.; Gorycki, P.D.; Webb, E.F.; Hall, R.; Sorenson, M.; Lee, J.C.; Ayrton, A.; Griswold, D.E.; Gallagher, T.F.; Pyrimidinylimidazole inhibitors of CSBP/p38 kinase demonstrating decreased inhibition of hepatic cytochrome P450 enzymes. Bioorg Med Chem Lett 1998, 8, 22, 3111.
【2】 Adams, J.L.; Sheldrake, P.W.; Gallagher, T.F.; Garigipati, R.S.; Bender, P.E.; Boehm, J.C. (SmithKline Beecham plc); Tri-substd. imidazoles having multiple therapeutic properties. EP 0708768; WO 9502591 .
【3】 Garigipati, R.S.; Adams, J.L.; Boehm, J.C. (SmithKline Beecham Corp.); Pyridyl imidazole cpds. and compsns.. US 5670527 .
【4】 Adams, J.L.; Boehm, J.C.; Imidazole cpds., use and process of making. US 5593991 .

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)	25433	1,1-dimethoxyacetone	6342-56-9	C₅H₁₀O₃	详情	详情
(II)	25434	(E)-4-(dimethylamino)-1,1-dimethoxy-3-buten-2-one		C₈H₁₅NO₃	详情	详情
(III)	25435	4-(dimethoxymethyl)-2-pyrimidinylamine		C₇H₁₁N₃O₂	详情	详情
(IV)	25436	2-amino-4-pyrimidinecarbaldehyde		C₅H₅N₃O	详情	详情
(V)	12337	4-fluorobenzaldehyde	459-57-4	C₇H₅FO	详情	详情
(VI)	25437	4-methylphenylhydrosulfide	106-45-6	C₇H₈S	详情	详情
(VII)	25438	(4-fluorophenyl)[(4-methylphenyl)sulfanyl]methylformamide		C₁₅H₁₄FNOS	详情	详情
(VIII)	25439	4-Fluoro-alpha-(4-methylphenylsulfanyl)benzyl isocyanide		C₁₅H₁₂FNS	详情	详情
(IX)	25440	3-(4-morpholinyl)-1-propanamine	123-00-2	C₇H₁₆N₂O	详情	详情
(X)	25441	4-([[3-(4-morpholinyl)propyl]imino]methyl)-2-pyrimidinamine		C₁₂H₁₉N₅O	详情	详情

Extended Information