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【结 构 式】

【药物名称】LY-193239

【化学名称】7(S)-[2-(2-Aminothiazol-4-yl)-2(Z)-(methoxyimino)acetamido]-3-(methylsulfonyl)-8-oxo-1,5-diazabicyclo[3.3.0]oct-2-ene-2-carboxylic acid

【CA登记号】122620-17-1

【 分 子 式 】C14H16N6O7S2

【 分 子 量 】444.44762

【开发单位】Lilly (Originator)

【药理作用】Pyrazolidinones

合成路线1

The reaction of N-(tert-butoxycarbonyl)-L-serine methyl ester (I) with hydrazine gives the corresponding hydrazide (II), which is acylated with trifluorothioacetic acid S-ethyl ester (III), yielding the diacylated hydrazine (IV). The cyclization of (IV) by means of DEAD and PPh3 affords the pyrazolidinone (V), which is deacylated with NaOH to furnish 4(S)-(tert-butoxycarbonyl)pyrazolidin-3-one (VI). The condensation of (VI) with vinylphosphonate (VII) gives the adduct (VIII), which is cyclized with the oxalyl monoester chloride (IX) by means of DIEA, yielding the pyrazolopyrazole (X). Finally, this compound is deprotected in acid medium and acylated with thiazole derivative (XI) by means of a Pd(0) catalyst to furnish the target compound.

1 Ternansky, R.J.; Draheim, S.E.; The synthesis of bicyclic pyrazolidinone antibacterial agents. 30th Nat Org Symp (Vancouver) 1987.
2 Jungheim, L.N.; Holmes, R.E. (Eli Lilly and Company); Substd. diazolidinones. US 4826993 .
3 Jungheim, L.N.; Ternansky, R.J.; Holmes, R.E.; BICYCLIC PYRAZOLIDINONE ANTIBACTERIAL AGENTS. Drugs Fut 1990, 15, 2, 149.
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) 43221 methyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-hydroxypropanoate 2766-43-0 C9H17NO5 详情 详情
(II) 43222 tert-butyl (1S)-2-hydrazino-1-(hydroxymethyl)-2-oxoethylcarbamate C8H17N3O4 详情 详情
(III) 43223 S-ethyl 2,2,2-trifluoroethanethioate 383-64-2 C4H5F3OS 详情 详情
(IV) 43224 tert-butyl (1S)-1-(hydroxymethyl)-2-oxo-2-[2-(2,2,2-trifluoroacetyl)hydrazino]ethylcarbamate C10H16F3N3O5 详情 详情
(V) 43225 tert-butyl (4S)-3-oxo-1-(2,2,2-trifluoroacetyl)pyrazolidinylcarbamate C10H14F3N3O4 详情 详情
(VI) 43226 tert-butyl (4S)-3-oxopyrazolidinylcarbamate C8H15N3O3 详情 详情
(VII) 43230 diethyl 1-(methylsulfonyl)vinylphosphonate C7H15O5PS 详情 详情
(VIII) 43231 diethyl 2-[(4S)-4-[(tert-butoxycarbonyl)amino]-3-oxopyrazolidinyl]-1-(methylsulfonyl)ethylphosphonate C15H30N3O8PS 详情 详情
(IX) 15585 allyl 2-chloro-2-oxoacetate C5H5ClO3 详情 详情
(X) 43232 allyl (6S)-6-[(tert-butoxycarbonyl)amino]-2-(methylsulfonyl)-5-oxo-6,7-dihydro-1H,5H-pyrazolo[1,2-a]pyrazole-3-carboxylate C16H23N3O7S 详情 详情
(XI) 24316 2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetyl chloride C6H6ClN3O2S 详情 详情
Extended Information