N-phenyl-1-hydrazinecarboxamide -Drug Synthesis Database

【结构式】

【分子编号】43730

【品名】N-phenyl-1-hydrazinecarboxamide

【CA登记号】537-47-3

【分子式】C₇H₉N₃O

【分子量】151.16808

【元素组成】C 55.62% H 6% N 27.8% O 10.58%

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：(XIII)

The Diels-Alder condensation of maleic anhydride (I) with furan (II) gives the epoxytetrahydrophthalic anhydride (III), which is reduced with H2 over Pd/C, yielding the epoxyperhydrophthalic anhydride (IV). Further reduction of (IV) with NaBH4 affords the epoxyperhydrophthalide (V), which is submitted to a third reduction with DIBAL-H to provide the lactol (VI) as a racemic mixture that is resolved with menthol. The appropriate isomer (VIIa) is treated with triphenylphosphonium bromide (VIII) and potassium tert-amyloxide to give the 5,8-epoxyperhydro-2-benzopyran-3-ol (IX), which is condensed with 4-carboxybutyltriphenylphosphonium bromide (X) by means of potassium tert-amyloxide and esterified with Amberlist-15/MeOH, yielding the cis-5-heptenoic acid methyl ester (XI). The oxidation of the primary alcohol group of (XI) with pyridinium chlorochromate (PCC) in dichloromethane affords the aldehyde (XII), which is finally reductocondensed with 4-phenylsemicarbazide (XIII) by means of NaBH3CN and hydrolyzed with LiOH to furnish the target semicarbazide.

参考文献中间体

合成目标

【1】 Haslanger, M.F.; Han, W.-C.; Ogletree, M.L.; Hall, S.E.; Harris, D.N.; 9,11-Epoxy-9-homo-14-oxaprosta-5-enoic acid derivatives. Novel inhibitors of fatty acid cyclooxygenase. J Med Chem 1986, 29, 2335-2347.
【2】 Gougoutas, J.Z.; Sprague, P.W.; Harris, D.N.; Malley, M.F.; Heikes, J.E.; Greenberg, R.; Synthesis and in vitro pharmacology of 7-oxabicyclo[2.2.1]heptane analogues of thromboxane A2/PGH2. J Med Chem 1985, 28, 1580-1590.
【3】 Hedberg, A.; Hall, S.E.; Harris, D.N.; Ogletree, M.L.; 7-Oxabicycloheptane analogs: modulators of the arachidonate cascade. Drugs Fut 1988, 13, 2, 153.
【4】 Haslanger, M.F.; Greenberg, M.J.; Ogletree, M.L.; Nakane, M.; Garber, D.P.; Harris, D.N.; Reid, J.C.; Aza-substituted omega side chain modification of 7-oxabicyclo[2.2.1]heptane TxA2 receptor antagonists: Structure-activity relationships. Advances in Prostaglandin, Thromboxane and Leukotriene Research, vol. 15; O. Hayaishi and S. Yamamoto (Eds.). Raven Press: New York 1985, 291-293.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VIa)	43719	(1R,3S,6R,7S)-4,10-dioxatricyclo[5.2.1.0(2,6)]decan-3-ol		C₈H₁₂O₃	详情	详情
(VIb)	43720	(1R,3R,6R,7S)-4,10-dioxatricyclo[5.2.1.0(2,6)]decan-3-ol		C₈H₁₂O₃	详情	详情
(VIIa)	43721	(1R,2R,3S,6R,7S)-4,10-dioxatricyclo[5.2.1.0(2,6)]decan-3-ol		C₈H₁₂O₃	详情	详情
(VIIb)	43728	(1S,2S,3R,6S,7R)-4,10-dioxatricyclo[5.2.1.0(2,6)]decan-3-ol		C₈H₁₂O₃	详情	详情
(I)	11182	2,5-Furandione; Maleic anhydride	108-31-6	C₄H₂O₃	详情	详情
(II)	22372	Furan	110-00-9	C₄H₄O	详情	详情
(III)	43717	(1R,2R,6S,7S)-4,10-dioxatricyclo[5.2.1.0(2,6)]dec-8-ene-3,5-dione		C₈H₆O₄	详情	详情
(IV)	36472	(1R,2R,6S,7S)-4,10-dioxatricyclo[5.2.1.0(2,6)]decane-3,5-dione		C₈H₈O₄	详情	详情
(V)	43718	(1R,2R,6R,7S)-4,10-dioxatricyclo[5.2.1.0(2,6)]decan-3-one		C₈H₁₀O₃	详情	详情
(VIII)	25649	(methoxymethyl)(triphenyl)phosphonium bromide		C₂₀H₂₀BrOP	详情	详情
(IX)	43722	(1S,2R,5R,7R,8R)-4,11-dioxatricyclo[6.2.1.0(2,7)]undecan-5-ol		C₉H₁₄O₃	详情	详情
(X)	13616	(4-Carboxybutyl)triphenylphosphonium bromide	17814-85-6	C₂₃H₂₄BrO₂P	详情	详情
(XI)	43723	methyl (Z)-7-[(1R,2R,3R,4S)-3-(hydroxymethyl)-7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoate		C₁₅H₂₄O₄	详情	详情
(XII)	43729	methyl (Z)-7-[(1R,2R,3S,4S)-3-formyl-7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoate		C₁₅H₂₂O₄	详情	详情
(XIII)	43730	N-phenyl-1-hydrazinecarboxamide	537-47-3	C₇H₉N₃O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Reaction of the 3-(methylsulfanyl)benzodithiazine (I) with 4-phenylsemicarbazide (II) in boiling MeOH affords adduct (III). Subsequent cyclization of (III) with concomitant amide dehydration in boiling POCl3 furnishes the title tricyclic compound.

参考文献中间体

合成目标

【1】 Pomarnacka, E.; Gdaniec, M.; Synthesis and anticancer activity of 2-amino-8-chloro-5,5-dioxo[1,2,4]triazolo[2,3-b][1,4,2]benzodithiazine derivatives. Bioorg Med Chem 2003, 11, 7, 1259.

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)	65028	6-chloro-3-(methylsulfanyl)-1,1-dioxo-1H-1lambda~6~,4,2-benzodithiazine-7-carboxamide		C₉H₇ClN₂O₃S₃	详情	详情
(II)	43730	N-phenyl-1-hydrazinecarboxamide	537-47-3	C₇H₉N₃O	详情	详情
(III)	65029	3-(2-benzoylhydrazino)-6-chloro-1,1-dioxo-1H-1lambda~6~,4,2-benzodithiazine-7-carboxamide		C₁₅H₁₁ClN₄O₄S₂	详情	详情

Extended Information