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【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

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.

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.

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