(1R)-1-methylpropylamine; (2R)-2-butanamine -Drug Synthesis Database

【结构式】

【分子编号】38928

【品名】(1R)-1-methylpropylamine; (2R)-2-butanamine

【CA登记号】

【分子式】C₄H₁₁N

【分子量】73.13808

【元素组成】C 65.69% H 15.16% N 19.15%

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：(R)(-)-(IX)

The reaction of 4-hydroxypyridine-3-sulfonic acid (I) with POCl3 and PCl5 gives 4-chloropyridine-3-sulfonyl chloride (II), which is treated with ammonia at room temperature yielding the sulfonamide (III). The resulting sulfonamide (VIII) was heated with ammonia to afford 4-aminopyridine-3-sulfonamide (IV), which is cyclized with urea (V) to provide the pyridothiadiazinone (VI). The reaction of (XI) with P2S5 in pyridine gives the corresponding thione (VII), which is methylated with methyl iodide to furnish the methylsulfanyl compound (VII) (2). Finally, this compound (VIII) is condensed with the chiral intermediate (R)(-)-1-methylpropylamine (R)(-)-(IX) to afford the chiral (R)(-)-target compound. The condensation of the intermediate methylsulfanyl compound (VIII) with the chiral intermediate (S)(+)-1-methylpropylamine (S)(+)-(IX) to afford the chiral (S)(+)-target compound.

参考文献中间体

合成目标

【1】 Pirotte, B.; et al.; 3-(Alkylamino)-4H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxides as powerful inhibitors of insulin release from rat oancreatic B-cells: a new class of potassium channel openers?. J Med Chem 1993, 36, 21, 3211-13.
【2】 de Tullio, P.; Khelili, S.; Lebrun, P.; et al.; Preparation and pharmacological evaluation of the R- and S-enantiomers of 3-(2'-butylamino)-4H- and 3-(3'-methyl-2'-butylamino)-4H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxide, two tissue selective ATP-sensitive potassium channel openers. Bioorg Med Chem 1999, 7, 8, 1513.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(R)(-)-(IX)	38928	(1R)-1-methylpropylamine; (2R)-2-butanamine		C₄H₁₁N	详情	详情
(S)(+)-(IX)	38929	(1S)-1-methylpropylamine; (2S)-2-butanamine		C₄H₁₁N	详情	详情
(I)	28520	4-hydroxy-3-pyridinesulfonic acid		C₅H₅NO₄S	详情	详情
(II)	28521	4-chloro-3-pyridinesulfonyl chloride		C₅H₃Cl₂NO₂S	详情	详情
(III)	22151	4-chloro-3-pyridinesulfonamide		C₅H₅ClN₂O₂S	详情	详情
(IV)	38924	4-amino-3-pyridinesulfonamide		C₅H₇N₃O₂S	详情	详情
(V)	19310	urea	57-13-6	CH₄N₂O	详情	详情
(VI)	38925	1lambda(6)-pyrido[4,3-e][1,2,4]thiadiazine-1,1,3(2H,4H)-trione		C₆H₅N₃O₃S	详情	详情
(VII)	38926	3-thioxo-3,4-dihydro-2H-pyrido[4,3-e][1,2,4]thiadiazine-1,1(2H)-dione		C₆H₅N₃O₂S₂	详情	详情
(VIII)	38927	3-(methylsulfanyl)-2H-pyrido[4,3-e][1,2,4]thiadiazine-1,1(4H)-dione		C₇H₇N₃O₂S₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IX)

The condensation of 2,4-dimethoxy-6-methylphenylacetonitrile (I) with ethyl acetate in the presence of Na metal produced keto nitrile (II). This was cyclized to the amino pyrazole (III) upon treatment with hydrazine and HOAc in refluxing toluene. Subsequent condensation of amino pyrazole (III) with ethyl acetimidate (IV) gave amidine (V), which was converted to the required pyrazolo triazinone (VI) by reaction with diethyl carbonate and NaOEt. Chlorination of (VI) with POCl3 in the presence of N,N-dimethylaniline produced the chloro derivative (VII). This was finally condensed with amine (VIII) to furnish the title compound.

参考文献中间体

合成目标

【1】 He, L.; Arvanitis, A.G.; Chorvat, R.; Gilligan, P. (DuPont Pharmaceuticals Co.); Azolo triazines and pyrimidines. EP 1049699; WO 9938868 .

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)	43369	2-(2,4-dimethoxy-6-methylphenyl)acetonitrile		C₁₁H₁₃NO₂	详情	详情
(II)	43370	2-(2,4-dimethoxy-6-methylphenyl)-3-oxobutanenitrile		C₁₃H₁₅NO₃	详情	详情
(III)	43371	4-(2,4-dimethoxy-6-methylphenyl)-3-methyl-1H-pyrazol-5-ylamine; 4-(2,4-dimethoxy-6-methylphenyl)-3-methyl-1H-pyrazol-5-amine		C₁₃H₁₇N₃O₂	详情	详情
(IV)	43372	N-[4-(2,4-dimethoxy-6-methylphenyl)-3-methyl-1H-pyrazol-5-yl]ethanimidamide		C₁₅H₂₀N₄O₂	详情	详情
(V)	12831	ethyl ethanimidoate	1000-84-6	C₄H₉NO	详情	详情
(VI)	43372	N-[4-(2,4-dimethoxy-6-methylphenyl)-3-methyl-1H-pyrazol-5-yl]ethanimidamide		C₁₅H₂₀N₄O₂	详情	详情
(VII)	43373	8-(2,4-dimethoxy-6-methylphenyl)-2,7-dimethylpyrazolo[1,5-a][1,3,5]triazin-4(3H)-one		C₁₆H₁₈N₄O₃	详情	详情
(VIII)	43374	4-chloro-8-(2,4-dimethoxy-6-methylphenyl)-2,7-dimethylpyrazolo[1,5-a][1,3,5]triazine; 2-(4-chloro-2,7-dimethylpyrazolo[1,5-a][1,3,5]triazin-8-yl)-5-methoxy-3-methylphenyl methyl ether		C₁₆H₁₇ClN₄O₂	详情	详情
(IX)	38928	(1R)-1-methylpropylamine; (2R)-2-butanamine		C₄H₁₁N	详情	详情

Extended Information