4-Hydroxycarbazole; 9H-carbazol-4-ol -Drug Synthesis Database

【结构式】

【分子编号】29480

【品名】4-Hydroxycarbazole; 9H-carbazol-4-ol

【CA登记号】52602-39-8

【分子式】C₁₂H₉NO

【分子量】183.2096

【元素组成】C 78.67% H 4.95% N 7.65% O 8.73%

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：(I)

By condensation of 4-hydroxycarbazole (I) with epichlorohydrin (II) by means of NaOH in aqueous dioxane at 40 C to yield 4-(2,3-epoxypropoxy)carbazole (III), followed by treatment with isopropylamine (IV) in refluxing ethanol

参考文献中间体

合成目标

【1】 Weetman, D.F.; Castaner, J.; Carazolol. Drugs Fut 1977, 2, 11, 715.
【2】 Leinert, H.; et al. (Boehringer Ingelheim GmbH); Triyclic diphenylamines derivatives. CH 598216; DE 2240599; FR 2196165; GB 1369580; JP 49056973 .

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)	29480	4-Hydroxycarbazole; 9H-carbazol-4-ol	52602-39-8	C₁₂H₉NO	详情	详情
(II)	10146	Epichlorohydrin; 2-(Chloromethyl)oxirane	106-89-8	C₃H₅ClO	详情	详情
(III)	40171	9H-carbazol-4-yl 2-oxiranylmethyl ether; 4-(2-oxiranylmethoxy)-9H-carbazole	51997-51-4	C₁₅H₁₃NO₂	详情	详情
(IV)	23933	2-Propanamine; Isopropylamine	75-31-0	C₃H₉N	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

This compound has been obtained in two related ways: 1. The reaction of 2-(2-bromoethoxy)anisole (I) with benzylamine (II) by heating at 80 C gives the secondary amine (III), which is condensed with epichlorohydrin (IV) by heating at 60 C to yield the isopropanol derivative (V). The condensation of (V) with 4-hydroxycarbazole (VI) by means of K2CO3 in refluxing dioxane affords the adduct (VII), which is finally debenzylated by hydrogenolysis with H2 over Pd/C in ethanol/water. 2. The condensation of the secondary amine (III) with 4-(2,3-epoxypropoxy)carbazole (VIII) in refluxing ethanol gives the already reported adduct (VII), which is debenzylated as indicated.

参考文献中间体

合成目标

【1】 Seres, P.; Cselenyak, J.; Nagy, K.; Simig, G.; Gregor, T.; Nagy, P.K.; Greff, Z.; Balazs, L.; Barkoczy, J.; Vereczkey, G.D.; Nemeth, N.; Szabo, T.; Ratkai, Z.; Doman, I. (Egis Pharmaceuticals Ltd.); Process and intermediates for preparing 1-[9'H-carbazol-4'-yloxy]-3-[2''-(2'''-methoxy-phenoxy)ethyl]amino]-propan-2-ol (carvedilol). EP 0918055 .

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)	51402	2-(2-Bromoethoxy)methoxybenzene; 1-Bromo-2-(2-methoxyphenoxy)ethane	4463-59-6	C₉H₁₁BrO₂	详情	详情
(II)	15147	Benzylamine; Phenylmethanamine	100-46-9	C₇H₉N	详情	详情
(III)	30528	N-benzyl-2-(2-methoxyphenoxy)-1-ethanamine; N-benzyl-N-[2-(2-methoxyphenoxy)ethyl]amine		C₁₆H₁₉NO₂	详情	详情
(IV)	10146	Epichlorohydrin; 2-(Chloromethyl)oxirane	106-89-8	C₃H₅ClO	详情	详情
(V)	51403	1-[benzyl[2-(2-methoxyphenoxy)ethyl]amino]-3-chloro-2-propanol		C₁₉H₂₄ClNO₃	详情	详情
(VI)	29480	4-Hydroxycarbazole; 9H-carbazol-4-ol	52602-39-8	C₁₂H₉NO	详情	详情
(VII)	51404	1-[benzyl[2-(2-methoxyphenoxy)ethyl]amino]-3-(9H-carbazol-4-yloxy)-2-propanol		C₃₁H₃₂N₂O₄	详情	详情
(VIII)	40171	9H-carbazol-4-yl 2-oxiranylmethyl ether; 4-(2-oxiranylmethoxy)-9H-carbazole	51997-51-4	C₁₅H₁₃NO₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(X)

By condensation of substituted nicotinamide (VI) with the carbazolyoxymethyl-oxirane (XII) in hot methanol/water. The intermediates the nicotinamide (VI) and the oxirane (XII) have been obtained as follows: 1.- Nicotinamide (VI): The reaction of 4-hydroxybenzyl alcohol (I) with 2-nitropropane (II) by means of potassium tert-butoxide in hot diglyme gives 4-(2-methyl-2-nitropropyl)phenol (III), which is reduced to the corresponding amino derivative (IV) with H2 over Pd/C in methanol/ethanol/acetic acid. Finally, this compound is condensed with 6-chloronicotinamide (V) by means of K2CO3 in dimethylacetamide/isooctane. 2.- Oxirane (XII): The reaction of phenylhydrazine (VII) with cyclohexane-1,3-dione (VIII) by means of NaHCO3 in isopropanol/water gives the monohydrazone (IX), which is cyclized with hotpolyphosphoric acid yielding the 4-hydroxycarbazole (X). Finally, this compound is condensed with the glycidyl 3-nitrophenylsulfonate (XI) by means of K2CO3 in refluxing acetone.

参考文献中间体

合成目标

【1】 Crowell, T.A.; Evrard, D.A.; Jones, C.D.; Muehl, B.S.; Rito, C.J.; Shuker, A.J.; Thorpe, A.J.; Thrasher, K.J. (Eli Lilly and Company); Carbazole analogues as selective B3 adrenergic agonists. EP 0827746; WO 9809625 .

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)	29474	4-(hydroxymethyl)phenol; 4-hydroxyphenylmethanol 4-hydroxybenzenemethanol; 4-Hydroxybenzyl alcohol	623-05-2	C₇H₈O₂	详情	详情
(II)	21819	2-nitropropane	79-46-9	C₃H₇NO₂	详情	详情
(III)	29475	4-(2-methyl-2-nitropropyl)phenol		C₁₀H₁₃NO₃	详情	详情
(IV)	29476	4-(2-amino-2-methylpropyl)phenol	51706-55-9	C₁₀H₁₅NO	详情	详情
(V)	29477	6-chloronicotinamide	6271-78-9	C₆H₅ClN₂O	详情	详情
(VI)	29478	6-[4-(2-amino-2-methylpropyl)phenoxy]nicotinamide		C₁₆H₁₉N₃O₂	详情	详情
(VII)	11818	Phenyl hydrazine; 1-Phenylhydrazine	100-63-0	C₆H₈N₂	详情	详情
(VIII)	11244	1,3-Cyclohexanedione	504-02-9	C₆H₈O₂	详情	详情
(IX)	29479	3-hydroxy-2-cyclohexen-1-one N-phenylhydrazone		C₁₂H₁₄N₂O	详情	详情
(X)	29480	4-Hydroxycarbazole; 9H-carbazol-4-ol	52602-39-8	C₁₂H₉NO	详情	详情
(XI)	16259	(2S)oxiranylmethyl 3-nitrobenzenesulfonate; (S)-(+)-Glycidyl nosylate	115314-14-2	C₉H₉NO₆S	详情	详情
(XII)	29481	9H-carbazol-4-yl (2S)oxiranylmethyl ether; 4-[(2S)oxiranylmethoxy]-9H-carbazole		C₁₅H₁₃NO₂	详情	详情

Extended Information