1,3-dimethoxy-2-propanamine -Drug Synthesis Database

【结构式】

【分子编号】23336

【品名】1,3-dimethoxy-2-propanamine

【CA登记号】

【分子式】C₅H₁₃NO₂

【分子量】119.16376

【元素组成】C 50.4% H 11% N 11.75% O 26.85%

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：(IV)

Serinol (I) was protected with triphenylmethyl chloride giving the N-trityl derivative (II), which was O-methylated using CH3I and NaH to afford the bis(methyl ether) (III). Subsequent acid deprotection of the trityl group of (III) provided 1,3-dimethoxy-2-aminopropane (IV). The hydroxypyridone (V) was converted to the salt with cyclohexylamine (VI), and then treated with phosphoryl chloride to produce the 4-chloropyridone (VII), which was condensed with amine (IV) to yield the aminopyridone (VIII). Further treatment of (VIII) with phosphoryl chloride gave 2-chloropyridine (IX). The nitro group of (IX) was then reduced with iron powder and AcOH, and the resulting diamino pyridine (X) was treated with NaNO2 and AcOH to produce the triazolopyridine (XI). Finally, coupling of (XI) with 2-chloro-4,6-dimethylaniline (XII) in the presence of p-TsOH provided the title compound, which was isolated as the mesylate salt.

参考文献中间体

合成目标

【1】 Bakthavatchalam, R.; Arvanitis, A.G.; Beck, J.P.; Cain, G.A.; Chorvat, R.J.; Gilligan, P.J.; Olson, R.E. (DuPont Pharmaceuticals Co.); Arylamino fused pyridines and pyrimidines. EP 0935601; WO 9735539 .

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)	23333	2-amino-1,3-propanediol; serinol	534-03-2	C₃H₉NO₂	详情	详情
(II)	23334	2-(tritylamino)-1,3-propanediol		C₂₂H₂₃NO₂	详情	详情
(III)	23335	1,3-dimethoxy-N-trityl-2-propanamine		C₂₄H₂₇NO₂	详情	详情
(IV)	23336	1,3-dimethoxy-2-propanamine		C₅H₁₃NO₂	详情	详情
(V)	23337	4-hydroxy-6-methyl-3-nitro-2(1H)-pyridinone	4966-90-9	C₆H₆N₂O₄	详情	详情
(VI)	12294	Aniline; Phenylamine	62-53-3	C₆H₇N	详情	详情
(VII)	23339	4-chloro-6-methyl-3-nitro-2(1H)-pyridinone		C₆H₅ClN₂O₃	详情	详情
(VIII)	23340	4-[[2-methoxy-1-(methoxymethyl)ethyl]amino]-6-methyl-3-nitro-2(1H)-pyridinone		C₁₁H₁₇N₃O₅	详情	详情
(IX)	23341	2-chloro-N-[2-methoxy-1-(methoxymethyl)ethyl]-6-methyl-3-nitro-4-pyridinamine		C₁₁H₁₆ClN₃O₄	详情	详情
(X)	23342	2-chloro-N(4)-[2-methoxy-1-(methoxymethyl)ethyl]-6-methyl-3,4-pyridinediamine		C₁₁H₁₈ClN₃O₂	详情	详情
(XI)	23343	2-(4-chloro-6-methyl-1H-[1,2,3]triazolo[4,5-c]pyridin-1-yl)-3-methoxypropyl methyl ether		C₁₁H₁₅ClN₄O₂	详情	详情
(XII)	23344	2-chloro-4,6-dimethylaniline		C₈H₁₀ClN	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VIII)

Claisen condensation of 2,4-dichlorophenylacetonitrile (I) with ethyl acetate using of Na metal gave ketonitrile (II), which was reacted with hydrazine hydrate in the presence of AcOH to afford aminopyrazole (III). Subsequent condensation of (III) with ethyl acetimidate (IV) produced amidine (V). This was cyclized with diethyl carbonate and NaOEt to furnish the pyrazolotriazinone (VI). Chlorination of (VI) using phosphoryl chloride in N,N-dimethylaniline provided chloride (VII), which was finally coupled with 1,3-dimethoxy-2-aminopropane (VIII) to yield the title compound.

参考文献中间体

合成目标

【1】 Gilligan, P.J.; He, L.; Zaczek, R.; et al.; 4-(1,3-Dimethoxyprop-2-ylamino)-2,7-dimethyl-8-(2,4-dichlorophenyl)pyrazolo[1,5-a]-1,3,5-triazine: A potent, orally bioavailable CRF1 receptor antagonist. J Med Chem 2000, 43, 3, 449.
【2】 Arvanitis, A.G.; Chorvat, R.J. (DuPont Pharmaceuticals Co.); Azolo triazines and pyrimidines. US 6124289; WO 9803510 .

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)	28484	2,4.Dichlorobenzyl cyanide; 2-(2,4-Dichlorophenyl)acetonitrile	6306-60-1	C₈H₅Cl₂N	详情	详情
(II)	28485	2-(2,4-dichlorophenyl)-3-oxobutanenitrile		C₁₀H₇Cl₂NO	详情	详情
(III)	27688	4-(2,4-dichlorophenyl)-3-methyl-1H-pyrazol-5-amine		C₁₀H₉Cl₂N₃	详情	详情
(IV)	12831	ethyl ethanimidoate	1000-84-6	C₄H₉NO	详情	详情
(V)	28486	N-[4-(2,4-dichlorophenyl)-3-methyl-1H-pyrazol-5-yl]ethanimidamide		C₁₂H₁₂Cl₂N₄	详情	详情
(VI)	28487	8-(2,4-dichlorophenyl)-2,7-dimethylpyrazolo[1,5-a][1,3,5]triazin-4(3H)-one		C₁₃H₁₀Cl₂N₄O	详情	详情
(VII)	28488	4-chloro-8-(2,4-dichlorophenyl)-2,7-dimethylpyrazolo[1,5-a][1,3,5]triazine		C₁₃H₉Cl₃N₄	详情	详情
(VIII)	23336	1,3-dimethoxy-2-propanamine		C₅H₁₃NO₂	详情	详情

Extended Information