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【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

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).

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.

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