4-morpholinylamine; 4-morpholinamine -Drug Synthesis Database

【结构式】

【分子编号】35977

【品名】4-morpholinylamine; 4-morpholinamine

【CA登记号】4319-49-7

【分子式】C₄H₁₀N₂O

【分子量】102.13628

【元素组成】C 47.04% H 9.87% N 27.43% O 15.66%

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：(I)

The reaction of N-aminomorpholine (I) with potassium cyanide and formaldehyde in water gives N-morpholino-2-aminoacetonitrile (II), which is nitrosated by reaction with NaNO2 - HCl in water yielding N-nitroso-N-morpholino-2-aminoacetonitrile (III). Finally, this compound is cyclized by treatment with HCl in methanol.

参考文献中间体

合成目标

【1】 Nakai, Y. Fujita, T.; Tanayama, S.; Suzuki, Z.; Biotransformation of molsidomine, a new antianginal agent, in rats. Xenobiotica 1974, 4, 175-191.
【2】 Imashiro, Y.; Kanebo, T.; Masuda, K.; Mesionic compounds. I. Synthesis of 3-dialkylaminosydnonimines. Chem Pharm Bull 1970, 18, 1, 128-132.
【3】 Masuda, K.; Imashiro, Y.; Sydnonimine derivatives. DE 1620501; FR 1496056; GB 1116692; US 3312690 .
【4】 Blancafort, P.; Serradell, M.N.; Castañer, J.; Grau, M.; SIN-1. Drugs Fut 1983, 8, 1, 43-44.
【5】 Bossuyt, L.; Czernielewski, J.; Bewley, A.P.; Henry, I.; Richert, B.; Al Abadie, M.; Drugs Today 1972, 8, 1, 15-18.

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)	35977	4-morpholinylamine; 4-morpholinamine	4319-49-7	C₄H₁₀N₂O	详情	详情
(II)	35978	2-(4-morpholinylamino)acetonitrile		C₆H₁₁N₃O	详情	详情
(III)	35979	(4-Morpholinylnitrosoamino)acetonitrile; Acetonitrile, (4-morpholinylnitrosoamino)-; N-Nitrosomorpholinoaminoacetonitrile	26687-79-6	C₆H₁₀N₄O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(X)

The reductocondensation of 3-bromo-4-fluorobenzaldehyde (I) with morpholine (II) by means of NaBH(OAc)3 in dichloroethane gives 4-(3-bromo-4-fluorobenzyl)morpholine (III), which is condensed with N-methoxy-N-methylacetamide (IV) by means of BuLi in THF to yield 1-[2-fluoro-5-(4-morpholinylmethyl)phenyl]ethanone (V). The reaction of (V) with an excess diethyl carbonate (VI) by means of NaH affords the 3-oxopropanoate derivative (VII), which is treated with triethyl orthoformate (VIII) and Ac2O at 150 C to provide the ethoxymethylene compound (IX). The reaction of (IX) with morpholine-4-amine (X) in ethanol gives the aminomethylene derivative (XI), which is cyclized by means of NaH in hot THF to yield the quinolone-3-carboxylate (XII). Finally, this compound is condensed with 4-chlorobenzylamine (XIII) by heating at 190 C to afford the target quinolone-3-carboxamide.

参考文献中间体

合成目标

【1】 Pargas, R.E.M.; Tucker, J.A.; Schnute, M.E.; et al.; 1-Amino-4-oxo-1,4-dihydroquinolines with broad-spectrum antiherpetic activity. 41st Intersci Conf Antimicrob Agents Chemother (Dec 16 2001, Chicago) 2001, Abst F-1669.
【2】 Thaisrivongs, S.; Strohbach, J.W.; Turner, S.R.; Vaillancourt, V.A.; Tucker, J.A.; Schnute, M.E. (Pharmacia Corp.); Quinolinecarboxamides as antiviral agents. EP 1140850; US 6248739; WO 0040561 .

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)	51550	3-Bromo-4-fluorobenzaldehyde	77771-02-9	C₇H₄BrFO	详情	详情
(II)	10388	Morpholine	110-91-8	C₄H₉NO	详情	详情
(III)	53185	4-(3-bromo-4-fluorobenzyl)morpholine	n/a	C₁₁H₁₃BrFNO	详情	详情
(IV)	17426	N-methoxy-N-methylacetamide	78191-00-1	C₄H₉NO₂	详情	详情
(V)	53186	1-[2-fluoro-5-(4-morpholinylmethyl)phenyl]-1-ethanone	n/a	C₁₃H₁₆FNO₂	详情	详情
(VI)	17470	diethyl carbonate; diethylcarbonate	105-58-8	C₅H₁₀O₃	详情	详情
(VII)	53187	ethyl 3-[2-fluoro-5-(4-morpholinylmethyl)phenyl]-3-oxopropanoate	n/a	C₁₆H₂₀FNO₄	详情	详情
(VIII)	21304	Triethyl orthoformate; 1-(Diethoxymethoxy)ethane; Diethoxymethyl ethyl ether	122-51-0	C₇H₁₆O₃	详情	详情
(IX)	53188	ethyl (Z)-3-ethoxy-2-[2-fluoro-5-(4-morpholinylmethyl)benzoyl]-2-propenoate	n/a	C₁₉H₂₄FNO₅	详情	详情
(X)	35977	4-morpholinylamine; 4-morpholinamine	4319-49-7	C₄H₁₀N₂O	详情	详情
(XI)	53191	ethyl (Z)-2-[2-fluoro-5-(4-morpholinylmethyl)benzoyl]-3-(4-morpholinylamino)-2-propenoate	n/a	C₂₁H₂₈FN₃O₅	详情	详情
(XII)	53192	ethyl 1-(4-morpholinyl)-6-(4-morpholinylmethyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylate	n/a	C₂₁H₂₇N₃O₅	详情	详情
(XIII)	23378	(4-chlorophenyl)methanamine; 4-chlorobenzylamine	104-86-9	C₇H₈ClN	详情	详情

Extended Information