2,4,6,8-tetrachloropyrimido[5,4-d]pyrimidine -Drug Synthesis Database

【结构式】

【分子编号】36173

【品名】2,4,6,8-tetrachloropyrimido[5,4-d]pyrimidine

【CA登记号】

【分子式】C₆Cl₄N₄

【分子量】269.90376

【元素组成】C 26.7% Cl 52.54% N 20.76%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(I)

Reaction of 2,4,6,8-tetrachloropyrimido[5,4-d]pyrimidine (I) with diethylamine (II) yields (III), which is converted into RA-642 by heating with 2'-hydroxyethyl-2'-methoxyethylamine (IV).

参考文献中间体

合成目标

【1】 Roch, R.; Kadatz, R.; Ihrig, H.; DE 2300661 .
【2】 Pichler, L.; Heckel, A.; RA-642. Drugs Fut 1983, 8, 12, 1023.

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)	36173	2,4,6,8-tetrachloropyrimido[5,4-d]pyrimidine		C₆Cl₄N₄	详情	详情
(II)	24486	Diethylamine; N,N-Diethylamine	109-89-7	C₄H₁₁N	详情	详情
(III)	36174	2,6-dichloro-N(4),N(4),N(8),N(8)-tetraethylpyrimido[5,4-d]pyrimidine-4,8-diamine; N-[2,6-dichloro-8-(diethylamino)pyrimido[5,4-d]pyrimidin-4-yl]-N,N-diethylamine		C₁₄H₂₀Cl₂N₆	详情	详情
(IV)	36175	2-[(2-methoxyethyl)amino]-1-ethanol		C₅H₁₃NO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The reaction of 2,4,6,8-tetrachloropyrimido[5,4-d]pyrimidine (I) with piperidine (A) at room temperature gives 2,6-dichloro-4,8-di(N-piperidino)pyrimido[5,4-d]pyrimidine (II), which is treated with diethanolamine (B) at 200 C to yield 2,6-bis(diethanolamino)-4,8-di(N-piperidino)pyrimido[5,4-d])pyrimidine (III) (1). The reduction of (III) with Zn in hot formic or acetic acid or in hot aqueous HCl gives 2,6-bis(diethanolamino)-8-(N-piperidino)-1,2,3,4-tetrahydropyrimido[5,4-d]pyrimidine (IV), which is then dehydrogenated with I2 - KI in water.

参考文献中间体

合成目标

【1】 Castañer, J.; Serradell, M.N.; Blancafort, P.; Owen, R.T.; Mopidamol. Drugs Fut 1980, 5, 11, 550.
【2】 US 3322755 .
【3】 Fischer, F.G.; et al.; US 3031450 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	10158	Piperidine	110-89-4	C₅H₁₁N	详情	详情
(B)	24273	2-[(2-hydroxyethyl)amino]-1-ethanol	111-42-2	C₄H₁₁NO₂	详情	详情
(I)	36173	2,4,6,8-tetrachloropyrimido[5,4-d]pyrimidine		C₆Cl₄N₄	详情	详情
(II)	39202	2,6-dichloro-4,8-di(1-piperidinyl)pyrimido[5,4-d]pyrimidine		C₁₆H₂₀Cl₂N₆	详情	详情
(III)	39203	2-[[6-[bis(2-hydroxyethyl)amino]-4,8-di(1-piperidinyl)pyrimido[5,4-d]pyrimidin-2-yl](2-hydroxyethyl)amino]-1-ethanol	58-32-2	C₂₄H₄₀N₈O₄	详情	详情
(IV)	39204	2-[[6-[bis(2-hydroxyethyl)amino]-4-(1-piperidinyl)-5,6,7,8-tetrahydropyrimido[5,4-d]pyrimidin-2-yl](2-hydroxyethyl)amino]-1-ethanol		C₁₉H₃₅N₇O₄	详情	详情

合成路线3

该中间体在本合成路线中的序号：(III)

Pyrimidopyrimidine tetraone (I) was converted to the disodium salt (II), which was then treated with PCl5 in refluxing POCl3 to provide the tetrachloro pyrimidopyrimidine (III). Displacement of the more reactive 4- and 8-chlorine atoms of (III) by 4-methoxybenzylamine (IV) in THF at room temperature gave the 4,8-di(4-methoxybenzylamino) derivative (V). Finally, the remainig chlorine atoms of (V) were displaced by diethanolamine (VI) at 110 C, yielding the title compound.

参考文献中间体

合成目标

【1】 Barlow, H.C.; et al.; Resistance-modifying agents. Part 7: 2,6-Disubstituted-4,8-dibenzylaminopyrimido[5,4-d]pyrimidines that inhibit nucleoside transport in the presence of alpha1-acid glycoprotein (AGP). Bioorg Med Chem Lett 2000, 10, 6, 585.
【2】 Calvert, A.H.; Griffin, R.J.; Curtin, N.J.; Golding, B.T.; Newell, D.R. (University of Newcastle upon Tyne); Pyrimidopyrimidine cpds.. WO 9843974 .

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)	41123	1,5-dihydropyrimido[5,4-d]pyrimidine-2,4,6,8(3H,7H)-tetrone	6713-54-8	C₆H₄N₄O₄	详情	详情
(II)	41124	disodium 2,6-dioxo-1,2,6,7-tetrahydropyrimido[5,4-d]pyrimidine-4,8-diolate		C₆H₂N₄Na₂O₄	详情	详情
(III)	36173	2,4,6,8-tetrachloropyrimido[5,4-d]pyrimidine		C₆Cl₄N₄	详情	详情
(IV)	15098	4-Methoxybenzylamine; (4-Methoxyphenyl)methanamine	2393-23-9	C₈H₁₁NO	详情	详情
(V)	41125	2,6-dichloro-N(4),N(8)-bis(4-methoxybenzyl)pyrimido[5,4-d]pyrimidine-4,8-diamine; N-[2,6-dichloro-8-[(4-methoxybenzyl)amino]pyrimido[5,4-d]pyrimidin-4-yl]-N-(4-methoxybenzyl)amine		C₂₂H₂₀Cl₂N₆O₂	详情	详情
(VI)	24273	2-[(2-hydroxyethyl)amino]-1-ethanol	111-42-2	C₄H₁₁NO₂	详情	详情

合成路线4

该中间体在本合成路线中的序号：(V)

Condensation of 3,4-dimethoxybenzylamine (I) with 3,4-dimethoxybenzaldehyde (II) afforded imine (III), that was subsequently reduced to amine (IV) by means of NaBH4. Reaction of (V) with 2,4,6,8-tetrachloropyridopyrimidine (V) in THF at room temperature produced the 4,8-diamino derivative (VI). The remaining 2- and 6-chloro groups of (VI) were then displaced by aminoalcohol (VII) in boiling THF to furnish adduct (VIII). Finally, selective cleavage of two dimethoxybenzyl groups using trifluoroacetic acid gave rise to the title compound.

参考文献中间体

合成目标

【1】 Barlow, H.C.; et al.; Resistance-modifying agents. Part 7: 2,6-Disubstituted-4,8-dibenzylaminopyrimido[5,4-d]pyrimidines that inhibit nucleoside transport in the presence of alpha1-acid glycoprotein (AGP). Bioorg Med Chem Lett 2000, 10, 6, 585.

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)	13920	(3,4-Dimethoxyphenyl)methanamine; 3,4-Dimethoxybenzylamine; Veratrylamine	5763-61-1	C₉H₁₃NO₂	详情	详情
(II)	18304	3,4-Dimethoxybenzaldehyde; Veratraldehyde	120-14-9	C₉H₁₀O₃	详情	详情
(III)	41393	(3,4-dimethoxyphenyl)-N-[(E)-(3,4-dimethoxyphenyl)methylidene]methanamine; N-(3,4-dimethoxybenzyl)-N-[(E)-(3,4-dimethoxyphenyl)methylidene]amine		C₁₈H₂₁NO₄	详情	详情
(IV)	41394	N-(3,4-dimethoxybenzyl)(3,4-dimethoxyphenyl)methanamine; N,N-bis(3,4-dimethoxybenzyl)amine		C₁₈H₂₃NO₄	详情	详情
(V)	36173	2,4,6,8-tetrachloropyrimido[5,4-d]pyrimidine		C₆Cl₄N₄	详情	详情
(VI)	41395	N-[8-[bis(3,4-dimethoxybenzyl)amino]-2,6-dichloropyrimido[5,4-d]pyrimidin-4-yl]-N,N-bis(3,4-dimethoxybenzyl)amine; 2,6-dichloro-N(4),N(4),N(8),N(8)-tetrakis(3,4-dimethoxybenzyl)pyrimido[5,4-d]pyrimidine-4,8-diamine		C₄₂H₄₄Cl₂N₆O₈	详情	详情
(VII)	41397	1-amino-2-propanol	78-96-6	C₃H₉NO	详情	详情
(VIII)	41396	1-([4,8-bis[bis(3,4-dimethoxybenzyl)amino]-6-[(2-hydroxypropyl)amino]pyrimido[5,4-d]pyrimidin-2-yl]amino)-2-propanol		C₄₈H₆₀N₈O₁₀	详情	详情

Extended Information