2,3-dichloropyrazine -Drug Synthesis Database

【结构式】

【分子编号】32326

【品名】2,3-dichloropyrazine

【CA登记号】4858-85-9

【分子式】C₄H₂Cl₂N₂

【分子量】148.97876

【元素组成】C 32.25% H 1.35% Cl 47.59% N 18.8%

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：(I)

The reaction of 2,3-dichloropyrazine (I) with hexanethiol (II) by means of NaH in DMF/THF gives 2-chloro-3-(hexylsulfanyl)pyrazine (III), which is condensed with rac-exo-1-azabicyclo[2.2.1]heptan-3-ol (IV) by means of NaH in THF afforing the target compound as a racemic mixture that is submitted to optical resolution with tartaric acid. The intermediate -exo-1-azabicyclo[2.2.1]heptan-3-ol (IV) has been obtained as follows: The reduction of 1-azabicyclo[2.2.1]heptan-3-one (V) with H2 over PtO2in ethanol gives the corresponding endo-alcohol (VI), which is esterified under Mitsunobu conditions (PPh3, diisopropyl azodicarboxylate (DIAD) and benzoyl chloride) yielding the exo-benzoate (VII). The hydrolysis of (VII) with sodium methoxide in methanol affords the target exo-alcohol (IV).

参考文献中间体

合成目标

【1】 Abou-Gharbia, M.; Tokolics, J.; Stein, P.; Moyer, J.A.; Husbands, G.M.; Tasse, R.P.; Sabb, A.L.; Boast, C.A.; Discovery of a highly potent, functionally-selective muscarinic M1 agonist, WAY-132983 using rational drug design and receptor modelling. Bioorg Med Chem Lett 1999, 9, 14, 1895.

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)	32326	2,3-dichloropyrazine	4858-85-9	C₄H₂Cl₂N₂	详情	详情
(II)	32327	hexylhydrosulfide; 1-hexanethiol	111-31-9	C₆H₁₄S	详情	详情
(III)	32328	2-chloro-3-(hexylsulfanyl)pyrazine; 3-chloro-2-pyrazinyl hexyl sulfide		C₁₀H₁₅ClN₂S	详情	详情
(IV)	32329	(3S,4R)-1-azabicyclo[2.2.1]heptan-3-ol		C₆H₁₁NO	详情	详情
(V)	32330	(4R)-1-azabicyclo[2.2.1]heptan-3-one		C₆H₉NO	详情	详情
(VI)	32331	(3R,4R)-1-azabicyclo[2.2.1]heptan-3-ol		C₆H₁₁NO	详情	详情
(VII)	32332	(3S,4R)-1-azabicyclo[2.2.1]hept-3-yl benzoate		C₁₃H₁₅NO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

Displacement of the chloride group of 4-chloro-3-nitrobenzoic acid (I) with sodium disulfide, followed by reduction of the disulfide and nitro groups with Sn/HCl yields 3-amino-4-mercaptobenzoic acid (II), which is further esterified to (III) with methanolic HCl. Condensation of (III) with 2,3-dichloropyrazine (IV) produces the pyrazinobenzothiazine compound (V). The ester group of (V) is then reduced to alcohol (VI) employing LiAlH4. Subsequent treatment of alcohol (VI) with methanesulfonyl chloride and pyridine leads to the benzyl chloride (VII).

参考文献中间体

合成目标

【1】 Kaneko, T.; et al.; Inhibitors of adhesion molecules expression: The synthesis and pharmacological properties of 10H-pyrazino[2,3-b][1,4]benzothiazine derivatives. Chem Pharm Bull 2002, 50, 7, 922.
【2】 Kaneko, T.; Clark, R.; Ohi, N.; Ozaki, F.; Kawahara, T.; Kamada, A.; Okano, K.; Yokohama, H.; Muramoto, K.; Arai, T.; Ohkuro, M.; Takenaka, O.; Sonoda, J. (Eisai Co., Ltd.); Benzopiperidine derivs.. EP 0934941; WO 9806720 .

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)	14485	3-nitro-4-chlorobenzoic acid; 4-chloro-3-nitrobenzoic acid	96-99-1	C₇H₄ClNO₄	详情	详情
(II)	58451	3-amino-4-sulfanylbenzoic acid		C₇H₇NO₂S	详情	详情
(III)	58452	methyl 3-amino-4-sulfanylbenzoate		C₈H₉NO₂S	详情	详情
(IV)	32326	2,3-dichloropyrazine	4858-85-9	C₄H₂Cl₂N₂	详情	详情
(V)	58453	methyl 10H-pyrazino[2,3-b][1,4]benzothiazine-8-carboxylate		C₁₂H₉N₃O₂S	详情	详情
(VI)	58454	10H-pyrazino[2,3-b][1,4]benzothiazin-8-ylmethanol		C₁₁H₉N₃OS	详情	详情
(VII)	58455	8-(chloromethyl)-10H-pyrazino[2,3-b][1,4]benzothiazine		C₁₁H₈ClN₃S	详情	详情

Extended Information