ethyl isocyanate -Drug Synthesis Database

【结构式】

【分子编号】28738

【品名】ethyl isocyanate

【CA登记号】109-90-0

【分子式】C₃H₅NO

【分子量】71.07884

【元素组成】C 50.69% H 7.09% N 19.71% O 22.51%

与该中间体有关的原料药合成路线共 5 条

合成路线1 合成路线2 合成路线3 合成路线4 合成路线5

合成路线1

该中间体在本合成路线中的序号：(I)

The cyclization of ethyl isocyanate (I) with sodium azide (II) by means of AlCl3 in refluxing THF gives 1-ethyl-1,4-dihydro-5H-tetrazol-5-one (III), which is alkylated with 1-chloro-2-bromoethane (IV) by means of Na2CO3 and KI in refluxing 4-methyl-2-pentanone to afford 1-ethyl-4-(2-chloroethyl)-1,4-dihydro-5H-tetrazol-5-one (V). Finally, this compound is condensed with N-(4-methoxymethyl-4-piperidinyl)propionanilide (VI) by means of Na2CO4 - KI in refluxing 4-methyl-2-pentanone.

参考文献中间体

合成目标

【1】 Janssen, F. (Janssen Pharmaceutica NV); N-Phenyl-N-(4-piperidinyl)amides. DE 2819873; ES 469473; FR 2389622; GB 1598872; JP 53149980 .
【2】 Castaner, J.; Leeson, P.A.; Blancafort, P.; Mealy, N.E.; Serradell, M.N.; Alfentanil hydrochloride. Drugs Fut 1981, 6, 6, 335.

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)	28738	ethyl isocyanate	109-90-0	C₃H₅NO	详情	详情
(III)	32218	1-ethyl-1,4-dihydro-5H-1,2,3,4-tetraazol-5-one	69048-98-2	C₃H₆N₄O	详情	详情
(IV)	24271	1-bromo-2-chloroethane	107-04-0	C₂H₄BrCl	详情	详情
(V)	32219	1-(2-chloroethyl)-4-ethyl-1,4-dihydro-5H-1,2,3,4-tetraazol-5-one		C₅H₉ClN₄O	详情	详情
(VI)	32220	N-[4-(methoxymethyl)-4-piperidinyl]-N-phenylpropanamide		C₁₆H₂₄N₂O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：

The synthesis of tritiated cabergoline by two similar routes has been described: 1) The acylation of 6-nor-dihydrolysergic acid methyl ester (I) with propargyl bromide yields the corresponding 6-propargyl derivative (II), which is hydrogenated with tritium gas over Pd/C in the presence of quinoline to give the ditritiated 6-allyl derivative (III). This compound is treated with 3-(dimethylamino)propylamine at 120 C, yielding the amide (IV), which is finally treated with ethyl isocyanate. 2) The reaction of the propargyl derivative (II) with 3-(dimethylamino)propylamine as before gives the amide (V). The reaction of (V) with ethyl isocyanate gives compound (VI), which is then hydrogenated with tritium as before.

参考文献中间体

合成目标

【1】 Mantegani, S.; Brambilla, E.; Ermoli, A.; Fontana, E.; Angiuli, P.; Vicario, G.P.; Syntheses of tritium and carbon-14 labelled N-(3-dimethyl aminopropyl)-N-(ethylaminocarbonyl)-6-(2-propenyl)ergoline-8beta-carboxamide (cabergoline), a potent long lasting prolactin lowering agent. J Label Compd Radiopharm 1991, 29, 5, 519.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	11176	3-Bromopropyne; 3-Bromo-1-propyne	106-96-7	C₃H₃Br	详情	详情
	28738	ethyl isocyanate	109-90-0	C₃H₅NO	详情	详情
(I)	11273	8beta-Methoxycarbonylergoline; Methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate		C₁₆H₁₈N₂O₂	详情	详情
(II)	11274	methyl (6aR,9R,10aR)-7-(2-propynyl)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate		C₁₉H₂₀N₂O₂	详情	详情
(III)	11279	methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate		C₁₉H₂₂N₂O₂	详情	详情
(III)	63076	methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate		C₁₉H₂₂N₂O₂	详情	详情
(IV)	11276	(6aR,9R,10aR)-7-allyl-N-[3-(Dimethylamino)propyl]-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxamide		C₂₃H₃₂N₄O	详情	详情
(IV)	63077	(6aR,9R,10aR)-7-allyl-N-[3-(dimethylamino)propyl]-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxamide		C₂₃H₃₂N₄O	详情	详情
(V)	11277	(6aR,9R,10aR)-N-[3-(Dimethylamino)propyl]-7-(2-propynyl)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxamide		C₂₃H₃₀N₄O	详情	详情
(VI)	11278	N-[[(6aR,9R,10aR)-7-(2-Propynyl)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinolin-9-yl]carbonyl]-N-[3-(dimethylamino)propyl]-N'-ethylurea		C₂₆H₃₅N₅O₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(II)

This compound can be obtained by two differents ways: 1) By condensation of 6-allyl-N-[3-(dimethylamino)propyl]ergolin-8-beta-caboxamide (I) with ethyl isocyanate (II) in refluxing toluene. 2) By condensation of 6-allylergolin-8-beta-carboxylic acid (III) with N-ethyl-N'-[3-(dimethylamino)propyl]carbodiimide (IV) in refluxing THF.

参考文献中间体

合成目标

【1】 Temperilli, A.; Bernardi, L.; Brambilla, E. (Pharmacia Corp.); Regiospecific process for the preparation of ergoline derivatives. BE 0894060; JP 58038282 .
【2】 Salvati, P.; et al. (Pharmacia & Upjohn SpA); Composés dérivés de l'ergoline, procédé pour les préparer et leur usage comme médicaments. DE 3112861; FR 2479829 .
【3】 Serradell, M.N.; Azccheo, T.; Castaner, J.; Castaner, R.M.; Giudici, D.; Cabergoline. Drugs Fut 1987, 12, 9, 842.

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)	11276	(6aR,9R,10aR)-7-allyl-N-[3-(Dimethylamino)propyl]-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxamide		C₂₃H₃₂N₄O	详情	详情
(II)	28738	ethyl isocyanate	109-90-0	C₃H₅NO	详情	详情
(III)	28739	(6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylic acid		C₁₈H₂₀N₂O₂	详情	详情
(IV)	24945	N-[3-(dimethylamino)propyl]-N'-ethylcarbodiimide	25952-53-8	C₈H₁₇N₃	详情	详情

合成路线4

该中间体在本合成路线中的序号：(II)

The condensation of N-benzylpiperazine (I) with ethyl isocyanate (II) in refluxing ether gives N-ethyl-4-benzyl-1-piperazinecarboxamide (III), which is debenzylated by hydrogenolysis with H2 over Pd/C in ethanol - HCl yielding N'-ethyl-1-piperazinecarboxarnide (IV). Finally, this compound is condensed with 1,1-bis(4-fluorophenyl)-4-chlorobutane (V) by means of NaHCO3 in refluxing ethanol.

参考文献中间体

合成目标

【1】 Bjoerk, A.K.K.; Olsson, K.G.; Abramo, A.L.; Christensson, E.G.; DE 2941880 .
【2】 Gluchowski, C.; Chiu, G.; Marzabadi, M.R.; Nagarathnam, D.; Lagu, B.; Noble, S.; Wetzel, J.; Deleon, J.E. (Synaptic Pharmaceutical Corp.); Selective melanin concentrating hormone-1 (MCH1) receptor antagonists and uses thereof. EP 1299362; WO 0206245 .

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)	28542	N-Benzylpiperazine; 1-Benzylpiperazine	2759-28-6	C₁₁H₁₆N₂	详情	详情
(II)	28738	ethyl isocyanate	109-90-0	C₃H₅NO	详情	详情
(III)	37048	4-benzyl-N-ethyl-1-piperazinecarboxamide		C₁₄H₂₁N₃O	详情	详情
(IV)	37049	N-ethyl-1-piperazinecarboxamide		C₇H₁₅N₃O	详情	详情
(V)	37050	1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene	3312-04-7	C₁₆H₁₅ClF₂	详情	详情

合成路线5

该中间体在本合成路线中的序号：(V)

This compound can be obtained by two related ways (1,2): 1) The Grignard reaction of 2-amino-5-chlorobenzophenone (I) with methylmagnesium iodide in ether gives 2-amino-5-chloromethylbenzhydrol (II), which by reaction with ethyl isothiocyanate (III) in ether yields 2-(omega-ethylthioureido)-5-chloro-alpha-methylbenzhydrol (IV). Finally this compound is treated with mercuric oxide in refluxing ethanol. 2) The reaction of (II) with ethyl isocyanate (V) in ether gives 2-(omega-ethylureido)-5-chloro-alpha-methylbenzhydrol (VI), which is finally cyclized by treatment with aqueous 48% HBr at 100 C.

参考文献中间体

合成目标

【1】 Blancafort, P.; Serradell, M.N.; Castaner, J.; Neuman, M.; Etifoxine hydrochloride. Drugs Fut 1981, 6, 9, 550.
【2】 Kuch, H.; et al. (Farbwerke Hoechst A.G.); BE 707013; CA 870620; CH 502366; CH 522671; CH 532603; CH 532604; CH 534174; DE 1670772; FR 1571287; FR M7358; GB 1179856; GB 1197479; JP 7125385; JP 7126945; JP 7126946; JP 7126947; NL 6715652; US 3725404; ZA 6706887 .
【3】 Hoffman, I.; et al.; 2-Ethylamino-6-chloro-4-methyl-4-phenyl-4H-3,1,benzoxazine, a new psychotropic compound. Arzneim-Forsch 1970, 20, 7, 975.

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)	10279	(2-Amino-5-chlorophenyl)(phenyl)methanone; 2-Amino-5-chlorobenzophenone	719-59-5	C₁₃H₁₀ClNO	详情	详情
(II)	60956	1-(2-amino-5-chlorophenyl)-1-phenyl-1-ethanol		C₁₄H₁₄ClNO	详情	详情
(III)	60959	1-isothiocyanatoethane; ethyl isothiocyanate		C₃H₅NS	详情	详情
(IV)	60958	N-[4-chloro-2-(1-hydroxy-1-phenylethyl)phenyl]-N'-ethylthiourea		C₁₇H₁₉ClN₂OS	详情	详情
(V)	28738	ethyl isocyanate	109-90-0	C₃H₅NO	详情	详情
(VI)	60957	N-[4-chloro-2-(1-hydroxy-1-phenylethyl)phenyl]-N'-ethylurea		C₁₇H₁₉ClN₂O₂	详情	详情

Extended Information