sodium 2-(methylamino)-1-ethanesulfonate -Drug Synthesis Database

【结构式】

【分子编号】11821

【品名】sodium 2-(methylamino)-1-ethanesulfonate

【CA登记号】4316-74-9

【分子式】C₃H₈NNaO₃S

【分子量】161.157228

【元素组成】C 22.36% H 5% N 8.69% Na 14.27% O 29.78% S 19.9%

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：(II)

Methylprednisolone suleptanate with and without radiolabeling can be prepared by two different ways: 1) The reaction of suberic acid (I) with pivaloyl chloride and triethylamine followed by condensation with N-methyltaurine sodium salt (II) gives 8-oxo-8-[N-(2-sulfoethyl)-N-methylamino]octanoic acid (III), which is treated with triethylamine and HCl, affording the corresponding triethylammonium salt (IV). The condensation of (IV) with methylprednisolone (V) by means of pivaloyl chloride and dimethylaminopyridine (DMAP) in dichloromethane yields the intermediate triethylammonium salt (VI), which is finally treated with sodium hydrogen sulfate in water. 2) The reaction of 21-deoxy-21-iodomethylprednisolone (VII) with suberic acid (I) by means of diisopropylethylamine (DEA) in DMF yields the corresponding 21-hemisuberate (VIII), which is then condensed with N-methyltaurine sodium salt (II) by means of isobutyl chloroformate and triethylamine in THF.

参考文献中间体

合成目标

【1】 Anderson, B.D.; Conradi, R.A.; Knuth, K.E.; Strategies in the design of solution-stable, water-soluble prodrugs I: A physical-organic approach to pro-moiety selection for 21-esters of corticosteroids. J Pharm Sci 1985, 74, 365-74.
【2】 Graul, A.; Leeson, J.; Castaner, J.; Methylprednisolone Suleptanate. Drugs Fut 1997, 22, 8, 833.
【3】 Anderson, B.D.; Conradi, R.A. (Pharmacia Corp.); Sulfonate containing ester prodrugs of corticosteroids. JP 1984137500; US 4472392 .
【4】 Pearlman, B.A. (Pharmacia Corp.); Amine salts of alkane-1,n-dicarboxylic acid mono-(2-sulfato-ethyl)amides. WO 8900558 .

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)	11820	Suberic acid; Cork acid; Octanedioic acid	505-48-6	C₈H₁₄O₄	详情	详情
(II)	11821	sodium 2-(methylamino)-1-ethanesulfonate	4316-74-9	C₃H₈NNaO₃S	详情	详情
(III)	11822	7-[N-Methyl-N-(2-sulfoethyl)carbamoyl]heptanoic acid disodium salt		C₁₁H₁₉NNaO₆S	详情	详情
(IV)	11823	N,N-diethyl-1-ethanaminium 2-[(7-carboxyheptanoyl)(methyl)amino]-1-ethanesulfonate		C₁₇H₃₆N₂O₆S	详情	详情
(V)	10394	Methylprednisolone	83-43-2	C₂₂H₃₀O₅	详情	详情
(VI)	11825	N,N-diethyl-1-ethanaminium 3-[(8-[2-[(6S,8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-6,10,13-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl]-2-oxoethoxy]-8-oxooctanoyl)(methyl)amino]-1-propanesulfonate		C₄₀H₆₆N₂O₁₀S	详情	详情
(VII)	11826	(6S,8S,9S,10R,11S,13S,14S,17R)-11,17-Dihydroxy-17-(2-iodoacetyl)-6,10,13-trimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one		C₂₂H₂₉IO₄	详情	详情
(VIII)	11827	sodium 8-[2-[(6S,8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-6,10,13-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl]-2-oxoethoxy]-8-oxooctanoate		C₃₀H₄₁NaO₈	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

3) The title product labeled at 1, 2 and 4 positions is synthesized starting from [1,2,4-3H]-methylprednisolone and using the method described in the preceding paragraph to finally yield [1,2,4-3H]-methylprednisolone suleptanate. 4) The title product [14C]-labeled at the CO groups of the suberic acid is synthesized starting from methylprednisolone 21-O-mesylate (IX), which is condensed with [1,8-14C]-suberic acid (X) by means of diisopropyl ethylamine in DMF to yield the corresponding hemisuberate (XI). Finally, this compound is condensed with N-methyltaurine sodium salt (II) by means of isobutyl chloroformate as before.

参考文献中间体

合成目标

【1】 Stolle, W.T.; Runge, T.A.; Hsi, R.S.P.; Synthesis of carbon-14 and tritium labeled methylprednisolone suleptanate. J Label Compd Radiopharm 1990, 28, 255-80.
【2】 Graul, A.; Leeson, J.; Castaner, J.; Methylprednisolone Suleptanate. Drugs Fut 1997, 22, 8, 833.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(II)	11821	sodium 2-(methylamino)-1-ethanesulfonate	4316-74-9	C₃H₈NNaO₃S	详情	详情
(IX)	11828	2-[(6S,8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-6,10,13-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl methanesulfonate		C₂₃H₃₂O₇S	详情	详情
(X)	11820	Suberic acid; Cork acid; Octanedioic acid	505-48-6	C₈H₁₄O₄	详情	详情
(X)	45087	suberic acid		C₈H₁₄O₄	详情	详情
(XI)	11830	8-[2-[(6S,8S,9S,10R,11S,13S,14S,17R)-11,17-Dihydroxy-6,10,13-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl]-2-oxoethoxy]-8-oxooctanoic acid		C₃₀H₄₂O₈	详情	详情
(XI)	45088	8-[2-[(6S,8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-6,10,13-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl]-2-oxoethoxy]-8-oxooctanoic acid		C₃₀H₄₂O₈	详情	详情

Extended Information