7-[[Amino(imino)methyl]amino]heptanamide -Drug Synthesis Database

【结构式】

【分子编号】10270

【品名】7-[[Amino(imino)methyl]amino]heptanamide

【CA登记号】

【分子式】C₈H₁₈N₄O

【分子量】186.25728

【元素组成】C 51.59% H 9.74% N 30.08% O 8.59%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(XI)

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：(V)

The synthesis of [14C]-labeled 15-deoxyspergualin trihydrochloride has been reported: The condensation of [14C]-labeled S-methylisothiourea (I) with 7-aminoheptanoic acid (II) by means of NaOH in water gives 7-guanidinoheptanoic acid (III), which is treated with Dowex 50W resin (H+ form) in refluxing methanol yielding the corresponding methyl ester (IV). The reaction of (IV) with concentrated NH4OH affords the amide (V), which is finally condensed with glyoxyloxyspermidine (VI) by means of glutaric acid in hot water (60 C), and purified by chromatography over Sephadex CM-25 (Na+ form).

参考文献中间体

合成目标

【1】 Dischino, D.D.; Synthesis of carbon-14 labeled (±) 15-deoxyspergualin trihydrochloride. J Label Compd Radiopharm 1995, 36, 11, 1097.

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)	10272	[[Amino(imino)methyl]sulfanyl]methane	2986-19-8	C₂H₆N₂S	详情	详情
(I)	44636	[[amino(imino)methyl]sulfanyl]methane		C₂H₆N₂S	详情	详情
(II)	10273	7-Aminoheptanoic acid	929-17-9	C₇H₁₅NO₂	详情	详情
(III)	10274	7-[[Amino(imino)methyl]amino]heptanoic acid		C₈H₁₇N₃O₂	详情	详情
(III)	44637	7-[[amino(imino)methyl]amino]heptanoic acid		C₈H₁₇N₃O₂	详情	详情
(IV)	10275	methyl 7-[[amino(imino)methyl]amino]heptanoate		C₉H₁₉N₃O₂	详情	详情
(IV)	44638	methyl 7-[[amino(imino)methyl]amino]heptanoate		C₉H₁₉N₃O₂	详情	详情
(V)	10270	7-[[Amino(imino)methyl]amino]heptanamide		C₈H₁₈N₄O	详情	详情
(V)	44639	7-[[amino(imino)methyl]amino]heptanamide		C₈H₁₈N₄O	详情	详情
(VI)	10271	N-[4-[(3-Aminopropyl)amino]butyl]-2,2-dihydroxyacetamide		C₉H₂₁N₃O₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(IX)

2) By an acid catalyzed condensation of 7-guanidinoheptanamide (IX) with an equivalent amount of glyoxylspermidine (X) in the presence of glutaric acid at 60 C for 8 h. Purification of the reaction mixture gives DSG in 39% yield.

参考文献中间体

合成目标

【1】 Umezawa, H.; Kuroda, H.; Nakamura, T.; Umeda, Y.; Iinuma, H.; Moriguchi, M.; Takeuchi, T.; Synthesis and antitumor activity of spergualin analogues. I. Chemical modification of 7-guanidino-3-hydroxyacyl moiety. J Antibiot 1985, 38, 7, 886-898.
【2】 Kondo, S.; Ikeda, Y.; Ikeda, D.; Iwasawa, H.; Umezawa, H.; Iinuma, H.; Umeda, Y.; The total synthesis of spergualin, an antitumor antibiotic. J Antibiot 1981, 34, 12, 1625-1627.
【3】 Umezawa, H.; Takeuchi, T.; Kondo, S. (Microbial Chemistry Research Foundation); (-)-15-Deoxyspergualin, process for the preparation thereof, and intermediate of the same. US 4525299 .
【4】 Fujii, A.; Iinuma, H.; Ikeda, D.; Kondo, S.; Nakamura, T.; Takeuchi, T.; Umezawa, H. (Microbial Chemistry Research Foundation); N-[4-(3-Aminopropyl)-aminobutyl]-2-(omega-guanidino-fatty-acid-amido)-2-substd.-ethanamide and salt thereof. BE 0894651; US 4518532; US 4658058 .
【5】 Inokai, K.; Fujii, A.; Takeuchi, T.; Umeda, Y.; Moriguchi, M.; Nakamura, T.; Umezawa, H. (Nippon Kayaku Co., Ltd.; Takara Shuzo Co., Ltd.); Spegualin-related nitrile cpds. and their preparation method. JP 1985178853 .
【6】 Suzuki, M.; Nishizawa, R.; Takei, M.; Yoshida, M. (Nippon Kayaku Co., Ltd.); Purification method of spergualin or its derivs.. JP 1984029652 .
【7】 Nakamura, T.; Moriguchi, M.; Inokai, K.; Umeda, Y.; Umezawa, H.; Takeuchi, T.; Fujii, A. (Nippon Kayaku Co., Ltd.; Takara Shuzo Co., Ltd.); Adduct of omega-guanidino fatty acid amide and glyoxylic acid, and its preparation method. JP 1985178852 .
【8】 Takeuchi, T.; Umezawa, H.; Kondo, S.; Nakamura, T.; Iinuma, H.; Ikeda, T.; Fujii, A. (Microbial Chemistry Research Foundation); (S)-7-Guanidino-3-hydroxyheptanamide and its synthesis method. JP 1982188562 .
【9】 Ikeda, D.; Nakamura, T.; Fujii, A.; Umezawa, H.; Kondo, S.; Iinuma, H.; Takeuchi, T. (Microbial Chemistry Research Foundation); N-[4-(3-Aminopropyl)aminobutyl]-2,2-dihydroxyethanamide and process for its synthesis. DE 3217693; GB 2100253 .
【10】 Takeuchi, T.; Fujii, A.; Nakamura, T.; Umeda, Y.; Moriguchi, M.; Umezawa, H. (Nippon Kayaku Co., Ltd.; Takara Shuzo Co., Ltd.); Method for producing glyoxylspermidine and the use thereof for the production of 15-deoxy spergualin-related cpds.. DE 3506330; US 4603015 .
【11】 Cheng, C.C.; Zee-Cheng, R.K.-Y.; Deoxyspergualin. Drugs Fut 1987, 12, 2, 113.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(V)	10274	7-[[Amino(imino)methyl]amino]heptanoic acid		C₈H₁₇N₃O₂	详情	详情
(VI)	10273	7-Aminoheptanoic acid	929-17-9	C₇H₁₅NO₂	详情	详情
(VII)	22892	N-(4-aminobutyl)-N-(3-aminopropyl)amine; N(1)-(3-aminopropyl)-1,4-butanediamine	124-20-9	C₇H₁₉N₃	详情	详情
(VIII)	22893	2,2-diethoxyacetic acid		C₆H₁₂O₄	详情	详情
(IX)	10270	7-[[Amino(imino)methyl]amino]heptanamide		C₈H₁₈N₄O	详情	详情
(X)	10271	N-[4-[(3-Aminopropyl)amino]butyl]-2,2-dihydroxyacetamide		C₉H₂₁N₃O₃	详情	详情

Extended Information