3,5-Dimethyl-1H-pyrazole-1-carboximidamide -Drug Synthesis Database

【结构式】

【分子编号】10268

【品名】3,5-Dimethyl-1H-pyrazole-1-carboximidamide

【CA登记号】

【分子式】C₆H₁₀N₄

【分子量】138.17236

【元素组成】C 52.16% H 7.29% N 40.55%

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：(IX)

The synthesis of racemic 15-deoxyspergualin and tritium-labeled compound has been described: The oxidation of N-(3-hydroxypropyl)carbamic acid tert-butyl ester (I) with pyridinium chlorochromate in dichloromethane gives N-(3-oxopropyl)carbamic acid tert-butyl ester (II), which is condensed with 4-(triphenylphosphonium)butyrate (III) by means of lithium bis(trimethylsilyl)amide in THF yielding 7-(tert-butoxycarbonylamino)-4-heptenoic acid (IV). The esterification of (IV) with N-hydroxysuccinimide (V) by means of dicyclohexylcarbodiimide and 1-hydroxybenzotriazole affords the corresponding ester (VI), which is treated with ammonia in methanol giving the corresponding amide (VII). The hydrolysis of (VII) with HCl in ethyl acetate yields 7-amino-4-heptenamide (VIII), which is treated with 3,5-dimethylpyrazole-1-carboxamidine (IX) and K2CO3 in methanol affording 7-guanidino-4-heptenamide (X). The reduction of (X) gives 7-guanidinoheptanamide (XI), which is finally condensed with glyoxylspermidine (XII) by means of glutaric acid in hot water. The tritium-labeled compound can also be obtained in the same way by performing the reduction of heptenamide (X) with tritium gas.

参考文献中间体

合成目标

【1】 Cook, D.J.; Tepper, M.A.; Saulnier, M.G.; Dischino, D.D.; Synthesis of tritium labeled (±) 15-deoxyspergualin trihydrochloride. J Label Compd Radiopharm 1993, 33, 2, 137.

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)	10260	tert-butyl N-(3-hydroxypropyl)carbamate	58885-58-8	C₈H₁₇NO₃	详情	详情
(II)	10261	tert-butyl N-(3-oxopropyl)carbamate		C₈H₁₅NO₃	详情	详情
(III)	10262	4-(triphenylphosphonio)butanoate		C₂₂H₂₂O₂P	详情	详情
(IV)	10263	(E)-7-[(tert-Butoxycarbonyl)amino]-4-heptenoic acid		C₁₂H₂₁NO₄	详情	详情
(V)	10264	1-Hydroxydihydro-1H-pyrrole-2,5-dione; N-Hydroxysuccinimide; 1-Hydroxy-2,5-pyrrolidinedione	6066-82-6	C₄H₅NO₃	详情	详情
(VI)	10265	tert-butyl N-[(E)-7-[(2,5-dioxo-1-pyrrolidinyl)oxy]-7-oxo-3-heptenyl]carbamate		C₁₆H₂₄N₂O₆	详情	详情
(VII)	10266	tert-butyl N-[(E)-7-amino-7-oxo-3-heptenyl]carbamate		C₁₂H₂₂N₂O₃	详情	详情
(VIII)	10267	(E)-7-Amino-4-heptenamide		C₇H₁₄N₂O	详情	详情
(IX)	10268	3,5-Dimethyl-1H-pyrazole-1-carboximidamide		C₆H₁₀N₄	详情	详情
(X)	10269	(E)-7-[[Amino(imino)methyl]amino]-4-heptenamide		C₈H₁₆N₄O	详情	详情
(XI)	10270	7-[[Amino(imino)methyl]amino]heptanamide		C₈H₁₈N₄O	详情	详情
(XI)	44635	7-[[amino(imino)methyl]amino]heptanamide		C₈H₁₈N₄O	详情	详情
(XII)	10271	N-[4-[(3-Aminopropyl)amino]butyl]-2,2-dihydroxyacetamide		C₉H₂₁N₃O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IX)

Reaction of furylandrostanediol (I) (J Chem Soc (C) 1966, 377) with bromoacetaldehyde diethylacetal (II) in the presence of NaH in refluxing tetahydrofuran provided ether (III). Subsequent acid hydrolysis of ethyl acetal of (III) gave aldehyde (IV), which was reduced to alcohol (V) with NaBH4. Coupling of (V) with phthalimide (VI) under Mitsunobu conditions produced the N-alkylated phthalimide (VII), and further hydrazinolysis yielded primary amine (VIII). The required guanidine function was finally introduced by treatment of (VIII) with 3,5-dimethyl-1-pyrazolylformamidinium nitrate (IX) in boiling EtOH.

参考文献中间体

合成目标

【1】 Quadri, L.; Bernardi, L.; Ferrari, P.; Gobbini, M.; Melloni, P.; Valentino, L. (Sigma-Tau Industrie Farmaceutiche Riunite SpA); Cyclopentanperhydrophenanthren-17beta-(3-furyl)-3-derivs. and pharmaceutical compsns. comprising same for the treatment of cardiovascular disorders. EP 0576915; JP 1994065284; US 5432169 .

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)	27462	(3S,5R,8R,9S,10S,13R,17R)-17-(3-furyl)-10,13-dimethylhexadecahydro-14H-cyclopenta[a]phenanthrene-3,14-diol		C₂₃H₃₄O₃	详情	详情
(II)	12113	2-Bromo-1-ethoxyethyl ethyl ether; 2-Bromo-1,1-diethoxyethane; Bromoacetaldehyde diethylacetal	2032-35-1	C₆H₁₃BrO₂	详情	详情
(III)	27463	(3S,5R,8R,9S,10S,13R,17R)-3-(2,2-diethoxyethoxy)-17-(3-furyl)-10,13-dimethylhexadecahydro-14H-cyclopenta[a]phenanthren-14-ol		C₂₉H₄₆O₅	详情	详情
(IV)	27464	2-[[(3S,5R,8R,9S,10S,13R,14S,17R)-17-(3-furyl)-14-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]acetaldehyde		C₂₅H₃₆O₄	详情	详情
(V)	27465	(3S,5R,8R,9S,10S,13R,17R)-17-(3-furyl)-3-(2-hydroxyethoxy)-10,13-dimethylhexadecahydro-14H-cyclopenta[a]phenanthren-14-ol		C₂₅H₃₈O₄	详情	详情
(VI)	12376	Phthalimide; 1H-Isoindole-1,3(2H)-dione; Isoindole-1,3-dione;Phthalic dicarboximide;Phenylimide;Isoindole-1,3-dione	85-41-6	C₈H₅NO₂	详情	详情
(VII)	27466	2-(2-[[(3S,5R,8R,9S,10S,13R,14S,17R)-17-(3-furyl)-14-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]ethyl)-1H-isoindole-1,3(2H)-dione		C₃₃H₄₁NO₅	详情	详情
(VIII)	27467	(3S,5R,8R,9S,10S,13R,17R)-3-(2-aminoethoxy)-17-(3-furyl)-10,13-dimethylhexadecahydro-14H-cyclopenta[a]phenanthren-14-ol		C₂₅H₃₉NO₃	详情	详情
(IX)	10268	3,5-Dimethyl-1H-pyrazole-1-carboximidamide		C₆H₁₀N₄	详情	详情

Extended Information