ethyl 2-cyanoacetylcarbamate -Drug Synthesis Database

【结构式】

【分子编号】48249

【品名】ethyl 2-cyanoacetylcarbamate

【CA登记号】

【分子式】C₆H₈N₂O₃

【分子量】156.1412

【元素组成】C 46.15% H 5.16% N 17.94% O 30.74%

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)

Condensation of 3,4,5-trichloro nitrobenzene (I) with 4-chlorobenzeneacetonitrile (II) by means of NaOH and N,N,N-triethylbenzylammonium chloride in THF yields substituted nitrobenzeneacetonitrile (III), which is subjected to hydrogenation over Pt/C in MeOH in the presence of thiophene to provide aniline (IV). Treatment of (IV) with HCl, HOAc and NaNO2, followed by reaction with ethyl N-(2-cyanoacetyl) carbamate (V) in AcOEt, furnishes ethyl carbamate derivative (VI), which is then subjected to cyclization by means of KOAc in refluxing HOAc to yield perhydro-3,5-dioxo-1,2,4-triazine derivative (VII). Hydrolysis of the nitrile moiety of (VII) by treatment with HCl in refluxing HOAc gives carboxylic acid (VIII), which is finally decarboxylated by heating in 2-mercaptoacetic acid to provide the desired product.

参考文献中间体

合成目标

【1】 Boeckx, G.M.; Sipido, V.; Raeymaekers, A.H.M. (Janssen Pharmaceutica NV); alpha-Aryl-4-(4,5-dihydro-3,5-dioxo-1,2,4-triazin-2(3H)-yl)benzeneacetonitriles. AU 8545664; EP 0170316; ES 8609284; ES 8705403; JP 1986043176; JP 1993017454; US 4631278 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(B)	13297	Thiophene	110-02-1	C₄H₄S	详情	详情
(A)	48246	N-benzyl-N,N-dipropyl-1-propanaminium chloride		C₁₆H₂₈ClN	详情	详情
(I)	48245	1,2,3-trichloro-5-nitrobenzene	20098-48-0	C₆H₂Cl₃NO₂	详情	详情
(II)	22871	2-(4-chlorophenyl)acetonitrile	140-53-4	C₈H₆ClN	详情	详情
(III)	48247	2-(4-chlorophenyl)-2-(2,6-dichloro-4-nitrophenyl)acetonitrile		C₁₄H₇Cl₃N₂O₂	详情	详情
(IV)	48248	2-(4-amino-2,6-dichlorophenyl)-2-(4-chlorophenyl)acetonitrile		C₁₄H₉Cl₃N₂	详情	详情
(V)	48249	ethyl 2-cyanoacetylcarbamate		C₆H₈N₂O₃	详情	详情
(VI)	48250	ethyl 2-cyano-2-((Z)-2-[3,5-dichloro-4-[(4-chlorophenyl)(cyano)methyl]phenyl]hydrazono)acetylcarbamate		C₂₀H₁₄Cl₃N₅O₃	详情	详情
(VII)	48251	2-[3,5-dichloro-4-[(4-chlorophenyl)(cyano)methyl]phenyl]-3,5-dioxo-1,2,4-triazinane-6-carbonitrile		C₁₈H₁₀Cl₃N₅O₂	详情	详情
(VIII)	48252	2-[3,5-dichloro-4-[(4-chlorophenyl)(cyano)methyl]phenyl]-3,5-dioxo-1,2,4-triazinane-6-carboxylic acid		C₁₈H₁₁Cl₃N₄O₄	详情	详情
(C)	12893	Ethanethioic S-acid		C₂H₄OS	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

Cyanoacetic acid (I) is condensed with urethane (II) in hot Ac2O to afford N ethoxycarbonyl-cyanoacetamide (III). Subsequent reaction of (III) with triethyl orthoformate yields alpha-cyano-beta-ethoxy-N-ethoxycarbonyl-acrylamide (IV). The ethoxy group of (IV) is then displaced with hydrazine hydrate in EtOH to produce the hydrazino acrylamide (V). Finally, thermal cyclization of (V) gives rise to the title pyrazolopyrimidine (1, 2).

参考文献中间体

合成目标

【1】 Hildick, B.G.; Shaw, G.; Purines, pyrimidines, and imidazoles. Part XXXVII. Some new syntheses of pyrazolo[3,4-d]pyrimidines, including allopurinol. J Chem Soc 1971, 9, 1610.
【2】 Shaw, G.; Baildon, S.; Lees, P. Sr.; Process for the preparation of biologically active cpds. as well as novel cpds.. DE 1814082 .

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)	12591	Cyanoacetic Acid; 2-Cyanoacetic acid	372-09-8	C₃H₃NO₂	详情	详情
(II)	24199	Ethyl carbamate; Urethane	51-79-6	C₃H₇NO₂	详情	详情
(III)	48249	ethyl 2-cyanoacetylcarbamate		C₆H₈N₂O₃	详情	详情
(IV)	63576	ethyl (E)-2-cyano-3-ethoxy-2-propenoylcarbamate		C₉H₁₂N₂O₄	详情	详情
(V)	63577	ethyl (E)-2-cyano-3-hydrazino-2-propenoylcarbamate		C₇H₁₀N₄O₃	详情	详情

Extended Information