(1R)-1,2-dimethylpropylamine; (2R)-3-methyl-2-butanamine -Drug Synthesis Database

【结构式】

【分子编号】38922

【品名】(1R)-1,2-dimethylpropylamine; (2R)-3-methyl-2-butanamine

【CA登记号】

【分子式】C₅H₁₃N

【分子量】87.16496

【元素组成】C 68.9% H 15.03% N 16.07%

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)(-)-(I)

The synthesis of the intermediates, the chiral amines (R)(-)-1,2-dimethylpropylamine (R)(-)-(I) and (S)(+)-1,2-dimethylpropylamine (S)(+)-(I) has been performed as follows: (R)(-)-1,2-Dimethylpropylamine (R)(-)-(I): The reaction of racemic 1,2-dimethylpropylamine (rac)(I) with 2(S)-(6-methoxynaphthalen-2-yl)propionic acid (S)(+)-(II) (S-naproxen) in ethanol gives the ammonium salt (III) as a diastereomeric mixture from which the (R,S)-diastereomer is obtained by successive crystallizations. Finally, this diastereomer is treated with NaOH in water to obtain the target (R)(-)-amine (R)(-)-(I). (S)(+)-1,2-Dimethylpropylamine (S)(+)-(I): The reaction of racemic 1,2-dimethylpropylamine (rac)-(I) with 2(S)-hydroxy-2-phenylacetic acid (S)(+)-(IV) (S-mandelic acid) in ethanol gives the ammonium salt (V) as a diastereomeric mixture from which the (S,S)-diastereomer is obtained by successive crystallizations. Finally, this diastereomer is treated with NaOH in water to obtain the target (S)(+)-amine (S)(+)-(I).

参考文献中间体

合成目标

【1】 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
(S)(+)-(IV)	12563	(2S)-2-Hydroxy-2-phenylethanoic acid; S-(+)-Mandelic acid	17199-29-0	C₈H₈O₃	详情	详情
(S)(+)-(II)	30839	(2S)-2-(6-methoxy-2-naphthyl)propionic acid;(S)-naproxen;(S)-6-Methoxy-alpha-methyl-2-naphthaleneacetic acid	22204-53-1	C₁₄H₁₄O₃	详情	详情
rac-(I)	38919	1,2-dimethylpropylamine; 3-methyl-2-butanamine		C₅H₁₃N	详情	详情
(R)(-)-(I)	38922	(1R)-1,2-dimethylpropylamine; (2R)-3-methyl-2-butanamine		C₅H₁₃N	详情	详情
(S)(+)-(I)	38923	(1S)-1,2-dimethylpropylamine; (2S)-3-methyl-2-butanamine		C₅H₁₃N	详情	详情
(III)	38920	3-methyl-2-butanaminium (2S)-2-(6-methoxy-2-naphthyl)propanoate		C₁₉H₂₇NO₃	详情	详情
(V)	38921	3-methyl-2-butanaminium (2S)-2-hydroxy-2-phenylethanoate		C₁₃H₂₁NO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(R)(-)-(I)

The reaction of 4-hydroxypyridine-3-sulfonic acid (VI) with POCl3 and PCl5 gives 4-chloropyridine-3-sulfonyl chloride (VII), which is treated with ammonia at room temperature yielding the sulfonamide (VIII). The resulting sulfonamide (VIII) was heated with ammonia to afford 4-aminopyridine-3-sulfonamide (IX), which is cyclized with urea (X) to provide the pyridothiadiazinone (XI). The reaction of (XI) with P2S5 in pyridine gives the corresponding thione (XII), which is methylated with methyl iodide to furnish the methylsulfanyl compound (XIII). Finally, this compound (XIII) is condensed with the chiral intermediate (R)(-)-1,2-dimethylpropylamine (R)(-)-(I) to afford the chiral (R)(-)-target compound. The condensation of the intermediate methylsulfanyl compound (XIII) with the chiral intermediate (S)(+)-1,2-dimethylpropylamine (S)(+)-(I) 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)(-)-(I)	38922	(1R)-1,2-dimethylpropylamine; (2R)-3-methyl-2-butanamine		C₅H₁₃N	详情	详情
(S)(+)-(I)	38923	(1S)-1,2-dimethylpropylamine; (2S)-3-methyl-2-butanamine		C₅H₁₃N	详情	详情
(VI)	28520	4-hydroxy-3-pyridinesulfonic acid		C₅H₅NO₄S	详情	详情
(VII)	28521	4-chloro-3-pyridinesulfonyl chloride		C₅H₃Cl₂NO₂S	详情	详情
(VIII)	22151	4-chloro-3-pyridinesulfonamide		C₅H₅ClN₂O₂S	详情	详情
(IX)	38924	4-amino-3-pyridinesulfonamide		C₅H₇N₃O₂S	详情	详情
(X)	19310	urea	57-13-6	CH₄N₂O	详情	详情
(XI)	38925	1lambda(6)-pyrido[4,3-e][1,2,4]thiadiazine-1,1,3(2H,4H)-trione		C₆H₅N₃O₃S	详情	详情
(XII)	38926	3-thioxo-3,4-dihydro-2H-pyrido[4,3-e][1,2,4]thiadiazine-1,1(2H)-dione		C₆H₅N₃O₂S₂	详情	详情
(XIII)	38927	3-(methylsulfanyl)-2H-pyrido[4,3-e][1,2,4]thiadiazine-1,1(4H)-dione		C₇H₇N₃O₂S₂	详情	详情

Extended Information