N-(5-chloro-2-methoxyphenyl)-3,5-bis(trifluoromethyl)benzenecarbohydrazonamide -Drug Synthesis Database

【结构式】

【分子编号】58515

【品名】N-(5-chloro-2-methoxyphenyl)-3,5-bis(trifluoromethyl)benzenecarbohydrazonamide

【CA登记号】

【分子式】C₁₆H₁₂ClF₆N₃O

【分子量】411.7340192

【元素组成】C 46.67% H 2.94% Cl 8.61% F 27.69% N 10.21% O 3.89%

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：(V)

The epoxidation of the octadienamide intermediate (I) (scheme no. 26150102b, intermediate (XXIV)) by means of ketone (II), Oxone, Bu4N HSO4 and Na2-EDTA in acetonitrile/water gives the epoxide (III), which is condensed with the pentanoic acid (IV) by means of DCC and DMAP in dichloromethane to yield the ester (V). Finally, this compound is deprotected and submitted to macrocyclization by means of piperidine in DMF to afford the target Cryptophycin 52.

参考文献中间体

合成目标

【1】 Hoard, D.W.; et al.; Synthesis of cryptophycin 52 using the shi epoxidation. Org Lett 2002, 4, 10, 1813.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	18905	2,2,2-trichloroethyl (2R)-3-(3-chloro-4-methoxyphenyl)-2-[[(2E,5S,6R,7E)-5-hydroxy-6-methyl-8-phenyl-2,7-octadienoyl]amino]propanoate	C₂₇H₂₉Cl₄NO₅	详情	详情
(II)	58313		C₁₂H₁₈O₆	详情	详情
(III)	58514	N-(5-chloro-2-methoxyphenyl)-3,5-bis(trifluoromethyl)benzamide	C₁₆H₁₀ClF₆NO₂	详情	详情
(IV)	36504	N,N,N-tributyl-1-butanaminium (2R)-3-(3-chloro-4-methoxyphenyl)-2-([(E,5S,6S)-5-hydroxy-6-[(2R,3S)-3-phenyloxiranyl]-2-heptenoyl]amino)propanoate	C₄₁H₆₃ClN₂O₆	详情	详情
(V)	58515	N-(5-chloro-2-methoxyphenyl)-3,5-bis(trifluoromethyl)benzenecarbohydrazonamide	C₁₆H₁₂ClF₆N₃O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

Acylation of 5-chloroanisidine (I) with 3,5-bis(trifluoromethyl)benzoyl chloride (II) affords benzamide (III). Treatment of amide (III) with PCl5, followed by reaction of the intermediate iminoyl chloride with hydrazine in THF generates the amidrazone (IV). Cyclization of (IV) with carbonyl diimidazole leads to triazolone (V). Finally, methyl ether cleavage in (V) employing pyridine hydrochloride at 225 C provides the target phenol compound.

参考文献中间体

合成目标

【1】 Romine, J.L.; et al.; 4,5-Diphenyltriazol-3-ones: Openers of large-conductance Ca2+-activated potassium (maxi-K) channels. J Med Chem 2002, 45, 14, 2942.
【2】 Meanwell, N.A.; Starrett, J.E. Jr.; Hewawasam, P.; Romine, J.L.; Martin, S.W.; Gribkoff, V.K. (Bristol-Myers Squibb Co.); Diphenyl oxadiazolones as potassium channel modulators. JP 2000516925; US 5869509; WO 9804135 .

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)	37092	5-chloro-2-methoxyphenylamine; 5-chloro-2-methoxyaniline	95-03-4	C₇H₈ClNO	详情	详情
(II)	18290	3,5-Bis(trifluoromethyl)benzoyl chloride	785-56-8	C₉H₃ClF₆O	详情	详情
(III)	58514	N-(5-chloro-2-methoxyphenyl)-3,5-bis(trifluoromethyl)benzamide		C₁₆H₁₀ClF₆NO₂	详情	详情
(IV)	58515	N-(5-chloro-2-methoxyphenyl)-3,5-bis(trifluoromethyl)benzenecarbohydrazonamide		C₁₆H₁₂ClF₆N₃O	详情	详情
(V)	58516	5-[3,5-bis(trifluoromethyl)phenyl]-4-(5-chloro-2-methoxyphenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one		C₁₇H₁₀ClF₆N₃O₂	详情	详情

Extended Information