2-isothiocyanatopropane -Drug Synthesis Database

【结构式】

【分子编号】28919

【品名】2-isothiocyanatopropane

【CA登记号】2253-73-8

【分子式】C₄H₇NS

【分子量】101.17232

【元素组成】C 47.49% H 6.97% N 13.84% S 31.69%

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：(VI)

The tetahydroimidazopyridine (I) is prepared by condensation of histamine with propionaldehyde in the presence of NaOH. The alkylation in position 1 or 3 is performed with ethyl bromide in a catalytic two-phase system, after protection of the amine group in position 5 as benzyloxycarbonyl derivative, and followed by removal of the protecting group by catalytic hydrogenation. The resulting amines (IVa-b) are then made to react with isopropyl isothiocyanate and the two regioisomers obtained are separated by crystallization.

参考文献中间体

合成目标

【1】 Acari, G.; Bernardi, L.; Falconi, G.; Scarponi, U. (Pharmacia Corp.); 4,5,6,7-Tetrahydroimidazo[4,5-c]pyridine derivatives. BE 0871985; DE 2849572; FR 2433022; GB 2028798; JP 55024158; US 4223146 .
【2】 Riva, F.; 386/1634. Drugs Fut 1985, 10, 2, 101.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IVa)	28915	benzyl 1,4-diethyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridine-5-carboxylate		C₁₈H₂₃N₃O₂	详情	详情
(IVb)	28916	benzyl 3,4-diethyl-3,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridine-5-carboxylate		C₁₈H₂₃N₃O₂	详情	详情
(Va)	28917	1,4-diethyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine		C₁₀H₁₇N₃	详情	详情
(Vb)	28918	3,4-diethyl-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine		C₁₀H₁₇N₃	详情	详情
(VIIa)	28920	1,4-diethyl-N-isopropyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridine-5-carbothioamide		C₁₄H₂₄N₄S	详情	详情
(VIIb)	28921	3,4-diethyl-N-isopropyl-3,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridine-5-carbothioamide		C₁₄H₂₄N₄S	详情	详情
(I)	28913	4-ethyl-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine		C₈H₁₃N₃	详情	详情
(II)	10101	Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene	501-53-1	C₈H₇ClO₂	详情	详情
(III)	28914	benzyl 4-ethyl-3,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridine-5-carboxylate		C₁₆H₁₉N₃O₂	详情	详情
(VI)	28919	2-isothiocyanatopropane	2253-73-8	C₄H₇NS	详情	详情

合成路线2

该中间体在本合成路线中的序号：

Fluorination of 4,5-dichloro-2-nitroaniline (I) with 1-fluoro-4-hydroxy-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoborate) (II) gave fluoroaniline (III). The nitro group of (III) was then reduced by hydrogenation over Raney-Ni to afford phenylenediamine (IV). This was cyclized with isopropyl isothiocyanate in the presence of 1-cyclohexyl-3-(2-morpholinoethyl)carbodiimide metho-p-toluenesulfonate as the desulfurizing agent to yield benzimidazole (V). Coupling with 1,2,3-tri-O-acetyl-5-deoxy-D-ribofuranose (VI) using trimethylsilyl triflate and N,O-bis(trimethylsilyl)acetamide produced a mixture of regioisomeric ribofuranosyl benzimidazoles (VII) and (VIII), which were separated by column chromatography. Finally, deprotection of the acetate esters from the major isomer (VII) with Na2CO3 provided the title compound.

参考文献中间体

合成目标

【1】 Chamberlain, S.D.; Koszalka, G.W.; Chan, J.H.; Townsend, L.B.; Tidwell, J.H.; Drach, J.C.; Freeman, G.A. (Glaxo Wellcome plc; University of Michigan); Benzimidazole derivs.. EP 0970100; WO 9835977 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	28919	2-isothiocyanatopropane	2253-73-8	C₄H₇NS	详情	详情
(I)	25175	4,5-dichloro-2-nitroaniline	6641-64-1	C₆H₄Cl₂N₂O₂	详情	详情
(II)	25176	1-fluoro-4-hydroxy-1,4-diazoniabicyclo[2.2.2]octane		C₆H₁₃FN₂O	详情	详情
(III)	25177	3,4-dichloro-2-fluoro-6-nitroaniline		C₆H₃Cl₂FN₂O₂	详情	详情
(IV)	25177	3,4-dichloro-2-fluoro-6-nitroaniline		C₆H₃Cl₂FN₂O₂	详情	详情
(IV)	25178	2-amino-4,5-dichloro-3-fluorophenylamine		C₆H₅Cl₂FN₂	详情	详情
(V)	25178	2-amino-4,5-dichloro-3-fluorophenylamine		C₆H₅Cl₂FN₂	详情	详情
(VI)	25179	5,6-dichloro-4-fluoro-N-isopropyl-1H-benzimidazol-2-amine		C₁₀H₁₀Cl₂FN₃	详情	详情
(VII)	25180	(2R,3R,4R,5R)-4-(acetoxy)-2-[5,6-dichloro-4-fluoro-2-(isopropylamino)-1H-benzimidazol-1-yl]-5-methyltetrahydro-3-furanyl acetate		C₁₉H₂₂Cl₂FN₃O₅	详情	详情
(VIII)	25181	(2R,3R,4R,5R)-4-(acetoxy)-2-[5,6-dichloro-7-fluoro-2-(isopropylamino)-1H-benzimidazol-1-yl]-5-methyltetrahydro-3-furanyl acetate		C₁₉H₂₂Cl₂FN₃O₅	详情	详情

Extended Information