|
【结 构 式】 
|
【分子编号】18731 【品名】3-pyridinylmethanamine; 3-pyridinylmethylamine 【CA登记号】3731-52-0 |
【 分 子 式 】C6H8N2 【 分 子 量 】108.143 【元素组成】C 66.64% H 7.46% N 25.9% |
合成路线1
该中间体在本合成路线中的序号：(II)By condensation of 4-methoxyisophthaloyl chloride (I) with 3-picolylamine (II) by means of triethylamine in refluxing THF.
| 【1】 Selleri, R.; et al.; New 4-hydroxyisophatlic acid derivatives having anticoagulant and fibrinolytic activity. Chimie Therapeutique 1971, 6, 3, 203-207. |
| 【2】 Orzalesi, G.; Selleri, T.; Picolylamides de l'acide 4-hydroxy-isophalique, leurs dérivés méthoxylé et éthoxylé et leur procédé de fabrication. BE 0851967; FR 2100850 . |
| 【3】 Orzalesi, G.; Selleri, T. (L. Manetti & Roberts SpA); Inhibitor of blood plate aggregation. US 3973026 . |
| 【4】 Blancafort, P.; Serradell, M.N.; Castaner, J.; Hopkins, S.J.; Picotamide. Drugs Fut 1980, 5, 1, 37. |
合成路线2
该中间体在本合成路线中的序号：(IV)The cyclization of acetamidine (I) with 2-cyano-3,3-bis(methylthio)-2-propenoic acid methyl ester (II) by means ot NaH in DMF gives 2-methyl-6-(methylthio)-4 oxo-1,4-dihydropyrimidine-5-carbonitrile (III), which is then condensed with 3-pyridylmethyl amine (IV) by refluxing in dimethoxyethane solution.
| 【1】 Bagli, J.F. (American Home Products Corp.); Amino-pyrimidine derivs.. EP 0130735; ES 8602694; JP 1985025974; US 4505910 . |
| 【2】 Prous, J.; Castaner, J.; Pelrinone hydrochloride. Drugs Fut 1988, 13, 8, 728. |
| 【3】 Bagli, J.; Bogri, T.; Palameta, B.; Rakhit, S.; Peseckis, S.; McQuillan, J.; Lee, D.K.; Chemistry and positive inotropic effect of pelrino. J Med Chem 1988, 31, 4, 814-23. |
| 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) | 15866 | ethanimidamide | C2H6N2 | 详情 | 详情 | |
| (II) | 22737 | methyl 2-cyano-3,3-bis(methylsulfanyl)acrylate | C7H9NO2S2 | 详情 | 详情 | |
| (III) | 22738 | 2-methyl-6-(methylsulfanyl)-4-oxo-1,4-dihydro-5-pyrimidinecarbonitrile | C7H7N3OS | 详情 | 详情 | |
| (IV) | 18731 | 3-pyridinylmethanamine; 3-pyridinylmethylamine | 3731-52-0 | C6H8N2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：A general synthesis of this entire class of thrombin inhibitors has been published recently. An alternative synthesis for the preparation of napsagatran is outlined in Scheme 21319301a: L-Aspartic acid is sulfonated with naphthalenesulfochloride to give the sulfonamide (I). Reaction of (I) with formaldehyde leads to the oxazolinone (II), which is reacted with N-cyclopropylglycine ethyl ester (III) to afford the aspartate (IV). Condensation of (IV) with the guanidine (IX) and saponification of the ethyl ester group provides napsagatran. For the preparation of the guanidine (IX), picolylamine is hydrogenated to give the racemic 3-aminomethyl-piperidine, from which the desired enantiomer (V) is isolated as dibenzoyltartrate by crystallization. Reaction of piperidine (V) with acetoacetate affords the protected piperidine (VI), which is amidinated with amidinotriazole (VII) to give the protected guanidine (VIII). Deprotection of (VIII) with hydrochloric acid provides the enantiomerically pure guanidine (IX) as dihydrochloride.
| 【1】 Banner, D.W.; Hilpert, K.; Ackermann, J.; et al.; Design and synthesis of potent and highly selective thrombin inhibitors. J Med Chem 1994, 37, 23, 3889-901. |
| 【2】 Gast, A.; Kirchhofer, D.; Soukup. M.; Roux, S.; Ackermann, J.; Hilpert, K.; Tschopp, T.B.; Schmid, G.; Napsagatran. Drugs Fut 1995, 20, 5, 476. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 12263 | Cyclopropylamine; Cyclopropanamine | 765-30-0 | C3H7N | 详情 | 详情 | |
| 13070 | L-Aspartic acid; (2S)-2-Aminobutanedioic acid | 56-84-8 | C4H7NO4 | 详情 | 详情 | |
| 16640 | Ethyl 2-bromoacetate; Ethyl bromoacetate | 105-36-2 | C4H7BrO2 | 详情 | 详情 | |
| 18731 | 3-pyridinylmethanamine; 3-pyridinylmethylamine | 3731-52-0 | C6H8N2 | 详情 | 详情 | |
| (I) | 16803 | (2S)-2-[(2-naphthylsulfonyl)amino]butanedioic acid | C14H13NO6S | 详情 | 详情 | |
| (II) | 16804 | 2-[(4S)-3-(2-naphthylsulfonyl)-5-oxo-1,3-oxazolan-4-yl]acetic acid | C15H13NO6S | 详情 | 详情 | |
| (III) | 16805 | ethyl 2-(cyclopropylamino)acetate | C7H13NO2 | 详情 | 详情 | |
| (IV) | 16806 | (3S)-4-[cyclopropyl(2-ethoxy-2-oxoethyl)amino]-3-[(2-naphthylsulfonyl)amino]-4-oxobutyric acid | C21H24N2O7S | 详情 | 详情 | |
| (V) | 16807 | (3S)hexahydro-3-pyridinylmethylamine; (3S)hexahydro-3-pyridinylmethanamine | C6H14N2 | 详情 | 详情 | |
| (VI) | 16808 | methyl (Z)-3-[[(3R)hexahydro-3-pyridinylmethyl]amino]-2-butenoate | C11H20N2O2 | 详情 | 详情 | |
| (VII) | 16809 | 1H-1,2,4-triazole-1-carboximidamide hydrochloride | C3H6ClN5 | 详情 | 详情 | |
| (VIII) | 16810 | methyl (Z)-3-[([(3S)-1-[amino(imino)methyl]piperidinyl]methyl)amino]-2-butenoate hydrochloride | C12H23ClN4O2 | 详情 | 详情 | |
| (IX) | 16811 | (3S)-3-(aminomethyl)-1-piperidinecarboximidamide | C7H16N4 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(VIII)Alkylation of diethyl malonate (I) with chloroethyl ether (II) in the presence of NaOEt in refluxing EtOH provided tetrahydropyran dicarboxylate (III). Hydrolysis of diester (III) with ethanolic KOH, and decarboxylation of the resulting diacid (IV) at 180 C gave tetrahydropyran-4-carboxylic acid (V). This was reduced to the alcohol (VI) on treatment with LiAlH4 in refluxing THF, and then converted into mesylate (VII) by reaction with metanesulfonyl chloride and triethylamine in THF. 3-(Aminomethyl)pyridine (VIII) was protected as the imine (X) by reaction with benzophenone (IX) in refluxing benzene with a Dean-Stark trap. Alkylation of imine (X) with mesylate (VII) in the presence of LDA in cold THF gave intermediate (XI) which, on acidic hydrolysis provided amine (XII). Reaction of (XII) with saturated aqueous HBr at 100 C in a pressure tube formed dibromide (XIII), which was basified with K2CO3 and heated to 80 C to provide the target quinuclidine.
| 【1】 Bencherif, M.; Lippiello, P.M.; Caldwell, W.S. (R.J. Reynolds Tobacco Co.); Depolarizing skeletal muscle relaxants. WO 9607410 . |
| 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) | 16829 | Diethyl malonate | 105-53-3 | C7H12O4 | 详情 | 详情 |
| (II) | 12060 | Bis(2-chloroethyl) ether; 1-Chloro-2-(2-chloroethoxy)ethane; 2,2'-Dichlorodiethyl ether | 111-44-4 | C4H8Cl2O | 详情 | 详情 |
| (III) | 18726 | diethyl tetrahydro-4H-pyran-4,4-dicarboxylate | C11H18O5 | 详情 | 详情 | |
| (IV) | 18727 | tetrahydro-4H-pyran-4,4-dicarboxylic acid | C7H10O5 | 详情 | 详情 | |
| (V) | 18728 | tetrahydro-2H-pyran-4-carboxylic acid | C6H10O3 | 详情 | 详情 | |
| (VI) | 18729 | tetrahydro-2H-pyran-4-ylmethanol | C6H12O2 | 详情 | 详情 | |
| (VII) | 18730 | tetrahydro-2H-pyran-4-ylmethyl methanesulfonate | C7H14O4S | 详情 | 详情 | |
| (VIII) | 18731 | 3-pyridinylmethanamine; 3-pyridinylmethylamine | 3731-52-0 | C6H8N2 | 详情 | 详情 |
| (IX) | 18732 | benzophenone | 119-61-9 | C13H10O | 详情 | 详情 |
| (X) | 18733 | N-(dibenzylene)(3-pyridinyl)methanamine; N-(dibenzylene)-N-(3-pyridinylmethyl)amine | C19H16N2 | 详情 | 详情 | |
| (XI) | 18734 | N-(dibenzylene)-N-[1-(3-pyridinyl)-2-tetrahydro-2H-pyran-4-ylethyl]amine; N-(dibenzylene)-1-(3-pyridinyl)-2-tetrahydro-2H-pyran-4-yl-1-ethanamine | C25H26N2O | 详情 | 详情 | |
| (XII) | 18735 | 1-(3-pyridinyl)-2-tetrahydro-2H-pyran-4-ylethylamine; 1-(3-pyridinyl)-2-tetrahydro-2H-pyran-4-yl-1-ethanamine | C12H18N2O | 详情 | 详情 | |
| (XIII) | 18736 | 5-bromo-3-(2-bromoethyl)-1-(3-pyridinyl)-1-pentanamine; 5-bromo-3-(2-bromoethyl)-1-(3-pyridinyl)pentylamine | C12H18Br2N2 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(VII)Diazotization of p-anisidine (I), followed by coupling of the resulting diazonium salt (II) with 3-tert-butyl-4-hydroxyanisole (III) produced azobenzene (IV). Subsequent protection of the hydroxyl group of (IV) with chloromethyl methyl ether in the presence of NaH afforded the methoxymethyl derivative (V). Aniline (VI) was then obtained by catalytic hydrogenation of (V) over Pd/C. Condensation of aniline (VI) with triphosgene, followed by reaction with 3-picolylamine (VII) gave rise to urea (VIII). The methoxymethyl protecting group of (VIII) was finally removed by treatment with methanolic HCl.
| 【1】 Nakao, K.; et al.; Quantitative structure-activity analyses of novel hydroxyphenylurea derivatives as antioxidants. Bioorg Med Chem 1998, 6, 6, 849. |
| 【2】 Suzuki, T.; Ohmizu, H.; Hashimura, Y.; Kubota, H.; Tanaka, K. (Tanabe Seiyaku Co., Ltd.); Phenol-derivs. having pharmaceutical activity and process for preparing the same. EP 0790240; JP 1998195037; US 5849732 . |
| 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) | 10478 | p-Anisidine; 4-Methoxyaniline; 4-Methoxyphenylamine | 104-94-9 | C7H9NO | 详情 | 详情 |
| (II) | 12149 | 1-(4-Methoxyphenyl)diazonium chloride | C7H7ClN2O | 详情 | 详情 | |
| (III) | 40700 | 2-(tert-butyl)-4-methoxyphenol | C11H16O2 | 详情 | 详情 | |
| (IV) | 40701 | 2-(tert-butyl)-4-methoxy-6-[(Z)-2-(4-methoxyphenyl)diazenyl]phenol | C18H22N2O3 | 详情 | 详情 | |
| (V) | 40702 | (Z)-1-[3-(tert-butyl)-5-methoxy-2-(methoxymethoxy)phenyl]-2-(4-methoxyphenyl)diazene; 3-(tert-butyl)-4-(methoxymethoxy)-5-[(Z)-2-(4-methoxyphenyl)diazenyl]phenyl methyl ether | C20H26N2O4 | 详情 | 详情 | |
| (VI) | 40703 | 3-(tert-butyl)-5-methoxy-2-(methoxymethoxy)phenylamine; 3-(tert-butyl)-5-methoxy-2-(methoxymethoxy)aniline | C13H21NO3 | 详情 | 详情 | |
| (VII) | 18731 | 3-pyridinylmethanamine; 3-pyridinylmethylamine | 3731-52-0 | C6H8N2 | 详情 | 详情 |
| (VIII) | 40704 | N-[3-(tert-butyl)-5-methoxy-2-(methoxymethoxy)phenyl]-N'-(3-pyridinylmethyl)urea | C20H27N3O4 | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(XIX)Displacement of the mesylate group of (XV) with N-methylpiperazine (XVI) produced the disubstituted piperazine (XVII). The tert-butyl ester of (XVII) was cleaved to the corresponding carboxylic acid (XVIII) by means of trifluoroacetic acid in CH2Cl2. Then coupling of (XVIII) with 3-(aminomethyl)pyridine (XIX) gave rise to the title amide.
| 【1】 Bavetsias, V.; et al.; The design and synthesis of water-soluble analogues of CB30865, a quinazolin-4-one-based antitumor agent. J Med Chem 2002, 45, 17, 3692. |
| 【2】 Bavetsias, V.; Jackman, A.; Skelton, L. (Cancer Research Campaign Technology Ltd.); Anti-cancer dihydroquinazoline derivs.. WO 0050417 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XV) | 46871 | tert-butyl 4-[[(7-chloro-3-methyl-2-[[(methylsulfonyl)oxy]methyl]-4-oxo-3,4-dihydro-6-quinazolinyl)methyl](2-propynyl)amino]benzoate | C26H28ClN3O6S | 详情 | 详情 | |
| (XVI) | 10061 | 1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine | 109-01-3 | C5H12N2 | 详情 | 详情 |
| (XVII) | 46872 | tert-butyl 4-[([7-chloro-3-methyl-2-[(4-methyl-1-piperazinyl)methyl]-4-oxo-3,4-dihydro-6-quinazolinyl]methyl)(2-propynyl)amino]benzoate | C30H36ClN5O3 | 详情 | 详情 | |
| (XVIII) | 46873 | 4-[([7-chloro-3-methyl-2-[(4-methyl-1-piperazinyl)methyl]-4-oxo-3,4-dihydro-6-quinazolinyl]methyl)(2-propynyl)amino]benzoic acid | C26H28ClN5O3 | 详情 | 详情 | |
| (XIX) | 18731 | 3-pyridinylmethanamine; 3-pyridinylmethylamine | 3731-52-0 | C6H8N2 | 详情 | 详情 |
合成路线7
该中间体在本合成路线中的序号：(IX)Lithiation of 1,3-bis(O-methoxymethyl)resorcinol (I) by means of n-butyllithium, followed by acylation with acetyl chloride, gave the protected acetophenone (II). Subsequent acid hydrolysis of the methoxymethyl protecting groups furnished diol (III). The 4-hydroxybenzofuran derivative (VI) was prepared by monoalkylation of (III) with ethyl bromoacetate (IV), followed by base-catalyzed cyclization of the resulting keto ester (V). Alkylation of the hydroxybenzofuran (VI) with 1,3-dibromopropane (VII) gave the bromopropyl ether (VIII). This was finally condensed with 3-picolylamine (IX) to produce the title compound.
| 【1】 Masubuchi, M.; et al.; Design and synthesis of novel benzofurans as a new class of antifungal agents targeting fungal N-myristoyltransferase. Part 1. Bioorg Med Chem Lett 2001, 11, 14, 1833. |
| 【2】 Fujii, T.; Tsujii, S.; Liu, P.; Ohtsuka, T.; Ebiike, H.; Masubuchi, M.; Aoki, Y.; Kawasaki, K. (F. Hoffmann-La Roche AG); Novel bicyclic cpds.. US 6376491; WO 0037464 . |
| 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) | 52123 | [3-(methoxymethoxy)phenoxy]methyl methyl ether; 1,3-bis(methoxymethoxy)benzene | C10H14O4 | 详情 | 详情 | |
| (II) | 52124 | 1-[2,6-bis(methoxymethoxy)phenyl]-1-ethanone | C12H16O5 | 详情 | 详情 | |
| (III) | 27511 | 1-(2,6-dihydroxyphenyl)-1-ethanone | 699-83-2 | C8H8O3 | 详情 | 详情 |
| (IV) | 16640 | Ethyl 2-bromoacetate; Ethyl bromoacetate | 105-36-2 | C4H7BrO2 | 详情 | 详情 |
| (V) | 52125 | ethyl 2-(2-acetyl-3-hydroxyphenoxy)acetate | C12H14O5 | 详情 | 详情 | |
| (VI) | 52126 | ethyl 4-hydroxy-3-methyl-1-benzofuran-2-carboxylate | C12H12O4 | 详情 | 详情 | |
| (VII) | 12581 | 1,3-Dibromopropane | 109-64-8 | C3H6Br2 | 详情 | 详情 |
| (VIII) | 52127 | ethyl 4-(3-bromopropoxy)-3-methyl-1-benzofuran-2-carboxylate | C15H17BrO4 | 详情 | 详情 | |
| (IX) | 18731 | 3-pyridinylmethanamine; 3-pyridinylmethylamine | 3731-52-0 | C6H8N2 | 详情 | 详情 |
合成路线8
该中间体在本合成路线中的序号：(IV)Alkylation of ethyl 4-hydroxy-3-methylbenzofuran-2-carboxylate (I) with 1,3-dibromopropane (II) in the presence of K2CO3 produced the bromopropyl ether (III). Subsequent displacement of the remaining bromine of (III) with 3-picolylamine (IV) furnished the secondary amine (V). The ester group of (V) was then reduced to alcohol (VI) with LiAlH4. Finally, Mitsunobu coupling of alcohol (VI) with 2,4-difluorophenol (VII) in the presence of 1,1'-(azodicarbonyl)dipiperidine and tributylphosphine gave rise to the target difluorophenyl ether.
| 【1】 Ebiike, H.; Masubuchi, M.; Liu, P.; Kawasaki, K.,-I.; Morikami, K.; Sogabe, S.; Hayase, M.; Fujii, T.; Sakata, K.; Shindoh, H.; Shiratori, Y.; Aoki, Y.; Ohtsuka, T.; Shimma, N.; Design and synthesis of novel benzofurans as a new class of antifungal agents targeting fungal N-myristoyltransferase. Part 2. Bioorg Med Chem Lett 2002, 12, 4, 607. |
| 【2】 Fujii, T.; Tsujii, S.; Liu, P.; Ohtsuka, T.; Ebiike, H.; Masubuchi, M.; Aoki, Y.; Kawasaki, K. (F. Hoffmann-La Roche AG); Novel bicyclic cpds.. US 6376491; WO 0037464 . |
| 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) | 52126 | ethyl 4-hydroxy-3-methyl-1-benzofuran-2-carboxylate | C12H12O4 | 详情 | 详情 | |
| (II) | 12581 | 1,3-Dibromopropane | 109-64-8 | C3H6Br2 | 详情 | 详情 |
| (III) | 52127 | ethyl 4-(3-bromopropoxy)-3-methyl-1-benzofuran-2-carboxylate | C15H17BrO4 | 详情 | 详情 | |
| (IV) | 18731 | 3-pyridinylmethanamine; 3-pyridinylmethylamine | 3731-52-0 | C6H8N2 | 详情 | 详情 |
| (V) | 52875 | ethyl 3-methyl-4-{3-[(3-pyridinylmethyl)amino]propoxy}-1-benzofuran-2-carboxylate | C21H24N2O4 | 详情 | 详情 | |
| (VI) | 52876 | (3-methyl-4-{3-[(3-pyridinylmethyl)amino]propoxy}-1-benzofuran-2-yl)methanol | C19H22N2O3 | 详情 | 详情 | |
| (VII) | 21486 | 2,4-difluorophenol | 367-27-1 | C6H4F2O | 详情 | 详情 |
合成路线9
该中间体在本合成路线中的序号：(IV)Condensation of ethyl 4-hydroxy-3-methylbenzofuran-2-carboxylate (I) with 1,3-dibromopropane (II) affords the benzofuran bromopropyl ether (III). Subsequent displacement of bromide (III) with 3-picolylamine (IV) yields amine (V). The ester group of (V) is then reduced with LiAlH4 to furnish alcohol (VI). Finally, Mitsunobu coupling between alcohol (VI) and 2,3,4-trifluorophenol (VII) in the presence of 1,1'-(azodicarbonyl)dipiperidine (ADDP) and tributylphosphine provides the title compound
| 【1】 Ebiike, H.; Masubuchi, M.; Kawasaki, K.-I.; et al.; Design and synthesis of novel N-myristoyltransferase inhibitors as antifungal agents. 224th ACS Natl Meet (Aug 18 2002, Boston) 2002, Abst MEDI 56. |
| 【2】 Ebiike, H.; Masubuchi, M.; Liu, P.; Kawasaki, K.,-I.; Morikami, K.; Sogabe, S.; Hayase, M.; Fujii, T.; Sakata, K.; Shindoh, H.; Shiratori, Y.; Aoki, Y.; Ohtsuka, T.; Shimma, N.; Design and synthesis of novel benzofurans as a new class of antifungal agents targeting fungal N-myristoyltransferase. Part 2. Bioorg Med Chem Lett 2002, 12, 4, 607. |
| 【3】 Fujii, T.; Tsujii, S.; Liu, P.; Ohtsuka, T.; Ebiike, H.; Masubuchi, M.; Aoki, Y.; Kawasaki, K. (F. Hoffmann-La Roche AG); Novel bicyclic cpds.. US 6376491; WO 0037464 . |
| 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) | 52126 | ethyl 4-hydroxy-3-methyl-1-benzofuran-2-carboxylate | C12H12O4 | 详情 | 详情 | |
| (II) | 12581 | 1,3-Dibromopropane | 109-64-8 | C3H6Br2 | 详情 | 详情 |
| (III) | 52127 | ethyl 4-(3-bromopropoxy)-3-methyl-1-benzofuran-2-carboxylate | C15H17BrO4 | 详情 | 详情 | |
| (IV) | 18731 | 3-pyridinylmethanamine; 3-pyridinylmethylamine | 3731-52-0 | C6H8N2 | 详情 | 详情 |
| (V) | 52875 | ethyl 3-methyl-4-{3-[(3-pyridinylmethyl)amino]propoxy}-1-benzofuran-2-carboxylate | C21H24N2O4 | 详情 | 详情 | |
| (VI) | 53876 | N-(5,6-dimethoxy-2,3-dihydro-1H-inden-2-yl)-N,N-dipropylamine; 5,6-dimethoxy-N,N-dipropyl-2-indanamine | n/a | C17H27NO2 | 详情 | 详情 |
| (VII) | 60408 | 2,3,4-trifluorophenol | C6H3F3O | 详情 | 详情 |
合成路线10
该中间体在本合成路线中的序号：(VI)Alkaline hydrolysis of ester (I), followed by chlorination of the resulting carboxylic acid (II) by means of oxalyl chloride furnishes the acid chloride (III). This is then treated with morpholine (IV) to provide the corresponding amide (V). Displacement of the bromide group of (V) with 3-(aminomethyl)pyridine (VI) leads to the secondary amine (VII), which is further protected as the N-Boc derivative (VIII) employing di-tert-butyl dicarbonate. Addition of the 2-lithiated benzimidazole (IX) to the morpholine amide (VIII) gives rise to ketone (X). The N-Boc group of (X) is finally cleaved by treatment with trifluoroacetic acid in CH2Cl2.
| 【1】 Kawasaki, K.; Masubuchi, M.; Morikami, K.; Sogabe, S.; Aoyama, T.; Ebiike, H.; Niizuma, S.; Hayase, M.; Fujii, T.; Sakata, K.; Shindoh, H.; Shiratori, Y.; Aoki,Y.; Ohtsuka, T.; Shimma, N.; Design and synthesis of novel benzofurans as a new class of antifungal agents targeting fungal N-myristoyltransferase. Part 3. Bioorg Med Chem Lett 2003, 13, 1, 87. |
| 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) | 51127 | 6-phenyl-1-(1-piperazinyl)-1-hexanone | C16H24N2O | 详情 | 详情 | |
| (II) | 63703 | 4-[(3-bromopropyl)oxy]-3-methyl-1-benzofuran-2-carboxylic acid | C13H13BrO4 | 详情 | 详情 | |
| (III) | 63704 | 4-[(3-bromopropyl)oxy]-3-methyl-1-benzofuran-2-carbonyl chloride | C13H12BrClO3 | 详情 | 详情 | |
| (IV) | 10388 | Morpholine | 110-91-8 | C4H9NO | 详情 | 详情 |
| (V) | 63705 | {4-[(3-bromopropyl)oxy]-3-methyl-1-benzofuran-2-yl}(4-morpholinyl)methanone | C17H20BrNO4 | 详情 | 详情 | |
| (VI) | 18731 | 3-pyridinylmethanamine; 3-pyridinylmethylamine | 3731-52-0 | C6H8N2 | 详情 | 详情 |
| (VII) | 63706 | [3-methyl-4-({3-[(3-pyridinylmethyl)amino]propyl}oxy)-1-benzofuran-2-yl](4-morpholinyl)methanone | C23H27N3O4 | 详情 | 详情 | |
| (VIII) | 63707 | 1,1-dimethylethyl 3-{[3-methyl-2-(4-morpholinylcarbonyl)-1-benzofuran-4-yl]oxy}propyl(3-pyridinylmethyl)carbamate | C28H35N3O6 | 详情 | 详情 | |
| (IX) | 63708 | [1-(2-propenyl)-1H-benzimidazol-2-yl]lithium | C10H9LiN2 | 详情 | 详情 | |
| (X) | 63709 | 1,1-dimethylethyl 3-[(3-methyl-2-{[1-(2-propenyl)-1H-benzimidazol-2-yl]carbonyl}-1-benzofuran-4-yl)oxy]propyl(3-pyridinylmethyl)carbamate | C34H36N4O5 | 详情 | 详情 |