amino(imino)methanesulfonic acid -Drug Synthesis Database

【结构式】

【分子编号】15984

【品名】amino(imino)methanesulfonic acid

【CA登记号】

【分子式】CH₄N₂O₃S

【分子量】124.12044

【元素组成】C 9.68% H 3.25% N 22.57% O 38.67% S 25.83%

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：(X)

1) The esterification of N-acetylneuraminic acid (I) with methanol/HCl gives the corresponding methyl ester (II), which is acetylated with acetic anhydride, pyridine and dimethylaminopyridine (DMAP) yielding the pentaacetate (III). The reaction of (III) with trimethylsilyl trifluoromethanesulfonate in ethyl acetate affords the 2,3-didehydro derivative (IV), which is treated with trimethylsilyl azide in butanol to give the 4-azido derivative (V). The selective deacetylation of (V) with sodium methoxide in methanol yields N-acetyl-4-azido-2,4-dideoxy-2,3-didehydroneuraminic acid methyl ester (VI), which is reduced with H2 over Lindlar catalyst (Pd-Pb) in water and treated with Dowex 8x2 resin to afford the N-acetyl-4-amino-2,4-dideoxy-2,3-didehydroneuraminic acid (VII). The reaction of (VII) with BrCN and sodium acetate in methanol gives the corresponding 4-cyanoamino derivative (VIII), which is converted into the final product by reaction with ammonium formate in aqueous NH4OH. 2) The amino derivative (VII) can be converted directly into the final product by reaction with amidinosulfonic acid (X), NaOH and K2CO3 in water. 3) The amino derivative (VII) can also be converted directly into the final product by reaction with pyrazole-1-carboxamidine (XI) and triethylamine in water.

参考文献中间体

合成目标

【1】 Chandler, M.; Bamford, M.J.; Conroy, R.; et al.; Synthesis of the potent influenza neuraminidase inhibitor 4-guanidino Neu5Ac2en. X-Ray molecular structure of 5-acetamido-4-amino-2,6-anhydro-3,4,5-trideoxy-D-erythro-L-gluco-nononic acid. J Chem Soc - Perkins Trans I 1995, 9, 7, 1173-80.
【2】 von Itzstein, M.; Wu, W.-Y.; Jin, B.; The synthesis of 2,3-didehydro-2,4-dideoxy-4-guanidinyl-N-acetylneuraminic acid: A potent influenza virus sialidase inhibitor. Carbohydr Res 1994, 259, 2, 301-5.
【3】 Fromtling, R.; Castaner, J.; Zanamivir. Drugs Fut 1996, 21, 4, 375.
【4】 Weir, N.G.; Chandler, M.; Bamford, M.J. (Glaxo Wellcome plc); Synthesis of N-acetyl neuraminic acid derivs. WO 9407885 .
【5】 Patel, V. (Glaxo Wellcome plc); Synthesis of N-acetyl neuraminic acid derivs. WO 9407886 .
【6】 Chandler, M.; Weir, N. (Glaxo Wellcome plc); Preparation of N-acetyl neuraminic derivs. WO 9312105 .

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)	15975	(2S,4S,5R,6R)-5-(acetamido)-2,4-dihydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]tetrahydro-2H-pyran-2-carboxylic acid	131-48-6	C₁₁H₁₉NO₉	详情	详情
(II)	15976	methyl (2S,4S,5R,6R)-5-(acetamido)-2,4-dihydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]tetrahydro-2H-pyran-2-carboxylate	50998-13-5	C₁₂H₂₁NO₉	详情	详情
(III)	15977	methyl (2R,4S,5S,6R)-5-(acetamido)-2,4-bis(acetoxy)-6-[(1S,2R)-1,2,3-tris(acetoxy)propyl]tetrahydro-2H-pyran-2-carboxylate		C₂₂H₃₁NO₁₄	详情	详情
(IV)	15978	methyl (3aS,4R,7aR)-2-methyl-4-[(1S,2R)-1,2,3-tris(acetoxy)propyl]-3a,7a-dihydro-4H-pyrano[3,4-d][1,3]oxazole-6-carboxylate		C₁₈H₂₃NO₁₀	详情	详情
(V)	15979	methyl (2R,3R,4S)-3-(acetamido)-4-azido-2-[(1S,2R)-1,2,3-tris(acetoxy)propyl]-3,4-dihydro-2H-pyran-6-carboxylate		C₁₈H₂₄N₄O₁₀	详情	详情
(VI)	15980	methyl (2R,3R,4S)-3-(acetamido)-4-azido-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylate		C₁₂H₁₈N₄O₇	详情	详情
(VII)	15981	(2R,3R,4S)-3-(acetamido)-4-amino-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid		C₁₁H₁₈N₂O₇	详情	详情
(VIII)	15982	(2R,3R,4S)-3-(acetamido)-4-(cyanoamino)-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid		C₁₂H₁₇N₃O₇	详情	详情
(IX)	15983	1H-pyrazole-1-carboximidamide	4023-00-1	C₄H₆N₄	详情	详情
(X)	15984	amino(imino)methanesulfonic acid		CH₄N₂O₃S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

The monosulfonation of orcinol (I) with 2-chlorobenzenesulfonyl chloride (II) in ethyl ether/aqueous NaHCO3 gives the monosulfonate (III), which is condensed with 4-(methanesulfonyloxymethyl)piperidine-1-carboxylic acid tert-butyl ester (IV) by means of NaH in DMF to yield the aryl ether (V). The deprotection of (V) with 4N HCl in dioxane affords the piperidine (VI), which is finally treated with amidinosulfonic acid (VII) and TEA in DMF. The 4-(methanesulfonyloxymethyl)piperidine-1-carboxylic acid tert-butyl ester (IV) has been obtained as follows: The reaction of piperidine-4-carboxylic acid (VIII) with Boc2O and NaHCO3 in dioxane/water gives the protected piperidine (IX), which is reduced at the carboxyl group by means of BH3/THF yielding the carbinol (X). Finally, this compound is mesylated with MsCl and TEA in dichloromethane to afford the target intermediate.

参考文献中间体

合成目标

【1】 Soll, R.M.; Spurlino, J.; Murphy, L.; Lu, T.; Salemme, F.R.; Bone, R.; Illig, C.R.; Tomczuk, B.E.; Structure-activity and crystallographic analysis of a new class of non-amide-based thrombin inhibitor. Bioorg Med Chem Lett 2000, 10, 1, 79.
【2】 Zetter, B.R.; Smith, R. (Children's Medical Center Corp.); Treatment of human prostate cancer with spermine. WO 9711691 .

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)	27257	5-Methyl-1,3-benzenediol; Orcinol	505-15-4	C₇H₈O₂	详情	详情
(II)	30817	2-chlorobenzenesulfonyl chloride	2905-23-9	C₆H₄Cl₂O₂S	详情	详情
(III)	30818	3-hydroxy-5-methylphenyl 2-chlorobenzenesulfonate		C₁₃H₁₁ClO₄S	详情	详情
(IV)	40396	tert-butyl 4-([[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]methyl)-1-piperidinecarboxylate		C₁₄H₂₇NO₃S	详情	详情
(V)	40397	tert-butyl 4-[(3-[[(2-chlorophenyl)sulfonyl]oxy]-5-methylphenoxy)methyl]-1-piperidinecarboxylate		C₂₄H₃₀ClNO₆S	详情	详情
(VI)	40398	3-methyl-5-(4-piperidinylmethoxy)phenyl 2-chlorobenzenesulfonate		C₁₉H₂₂ClNO₄S	详情	详情
(VII)	15984	amino(imino)methanesulfonic acid		CH₄N₂O₃S	详情	详情
(VIII)	17402	4-nipecotic acid;piperidine-4-carboxylic acid;p-nipecotic acid; Isonipecotic acid; Hexahydroisonicotinic acid; 4-Piperidinecarboxylic acid	498-94-2	C₆H₁₁NO₂	详情	详情
(IX)	17404	1-(tert-butoxycarbonyl)-4-piperidinecarboxylic acid; 1-BOC-piperidine-4-carboxylic acid; N-Boc-isonipecotic acid	84358-13-4	C₁₁H₁₉NO₄	详情	详情
(X)	40399	tert-butyl 4-(hydroxymethyl)-1-piperidinecarboxylate		C₁₁H₂₁NO₃	详情	详情

Extended Information