|
【结 构 式】 
|
【分子编号】15288 【品名】1-Chloroacetone; Chloroacetone 【CA登记号】78-95-5 |
【 分 子 式 】C3H5ClO 【 分 子 量 】92.5248 【元素组成】C 38.94% H 5.45% Cl 38.32% O 17.29% |
合成路线1
该中间体在本合成路线中的序号：(C)The reaction of (I) with chloroacetone (C) by means of K2CO3 in refluxing acetone gives (2-methylimidazol-1-yl)acetone (VI), which is nitrated with HNO3 and P2O5 affording the corresponding nitro compound (VII). Finally, this product is reduced with NaBH4 in methanol at room temperature.
| 【1】 Cosar, C.; Crisan, C.; Horclois, R.; Jacob, R.M.; Robert, J.; Tchelitcheff, S.; Vaupre,R.; Nitroimidazoles. Arzneim-Forsch Drug Res 1966, 16, 1, 23-29. |
| 【2】 Jeanmart, C.; Messer, M. (Aventis Pharma SA); Process for the preparation of 5-nitroimidazole derivatives. CH 513177; DE 2107423; FR 2079879; GB 1278758; NL 7101641 . |
| 【3】 Hillier, K.; Secnidazole. Drugs Fut 1979, 4, 4, 280. |
| 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) | 15670 | 2-Methylimidazole; 2-Methyl-1H-imidazole | 693-98-1 | C4H6N2 | 详情 | 详情 |
| (VI) | 33278 | (2-methylimidazol-1-yl)acetone; 1-(2-methyl-1H-imidazol-1-yl)acetone | C7H10N2O | 详情 | 详情 | |
| (VII) | 33279 | 1-(2-methyl-5-nitro-1H-imidazol-1-yl)acetone | C7H9N3O3 | 详情 | 详情 | |
| (C) | 15288 | 1-Chloroacetone; Chloroacetone | 78-95-5 | C3H5ClO | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)The cyclization of 2-amino-3-chloropyrazine (I) with chloroacetone (II) by means of triethylamine at 100 C gives 8-chloro-2-methylimidazo[1,2-a]pyrazine (III), which is treated with benzyl alcohol and NaOH in DMF to yield 8-benzyloxy-2-methylimidazo[1,2-a]pyrazine (IV). The nitrosation of (V) with butyl nitrite in refluxing dioxane affords 8-benzyloxy-3-nitroso-2-methylimidazo[1,2-a]pyrazine (V), which is finally reduced with Zn in acetic acid, and treated with HCl.
| 【1】 Bristol, J.A.; Puchalski, C. (Schering Corp.); Imidazo[1,2-a]pyridines and use. EP 0068378; ES 513431; US 4450164 . |
| 【2】 Castaner, J.; Serradell, M.N.; SCH-32651. Drugs Fut 1985, 10, 6, 474. |
| 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) | 29682 | 3-chloro-2-pyrazinylamine; 3-chloro-2-pyrazinamine | C4H4ClN3 | 详情 | 详情 | |
| (II) | 15288 | 1-Chloroacetone; Chloroacetone | 78-95-5 | C3H5ClO | 详情 | 详情 |
| (III) | 29683 | 8-chloro-2-methylimidazo[1,2-a]pyrazine | C7H6ClN3 | 详情 | 详情 | |
| (IV) | 18710 | Benzyl alcohol; Phenylmethanol | 100-51-6 | C7H8O | 详情 | 详情 |
| (V) | 29684 | 8-(benzyloxy)-2-methylimidazo[1,2-a]pyrazine; benzyl 2-methylimidazo[1,2-a]pyrazin-8-yl ether | C14H13N3O | 详情 | 详情 | |
| (VI) | 29685 | 8-(benzyloxy)-2-methyl-3-nitrosoimidazo[1,2-a]pyrazine; benzyl 2-methyl-3-nitrosoimidazo[1,2-a]pyrazin-8-yl ether | C14H12N4O2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(II)By condensation of the sodium salt of 1,3-dibutyl-xantine (I) with chloroacetone (II) in refluxing ethanol.
| 【1】 Rohte, O.; Khan, E.A.; Tauscher, M.; Brenner, G.; Goring, J. (SmithKline Beecham plc); 7-(Oxoalkyl)-1,3-dialkyl xanthines, and medicaments containing then. DE 2402908; DE 2462367 . |
| 【2】 Adams, J.L.; Gallagher, T.F.; Garigipati, R.S.; Boehm, J.C.; Sisko, J.; Peng, Z.-Q.; Lee, J.C.-L. (SmithKline Beecham plc); Certain 1,4,5-tri-substd. imidazole cpds. useful as cytokine. EP 0809499; JP 1998512555; US 5593992; WO 9621452 . |
| 【3】 Castaner, J.; Koch, H.; BRL-30892. Drugs Fut 1985, 10, 10, 809. |
合成路线4
该中间体在本合成路线中的序号：(III)The partial hydrolysis ot 2,3,4-trifluoronitrobenzene (I) with KOH in DMSO gives 2,3-difluoro-6-nitrophenol (II), which by condensation with chloroacetone (III) by means of K2CO3 - KI in refluxing acetone yields 2-acetonyloxy-3,4-difluoronitrobenzene (IV). The reductive cyclization of (IV) with H2 over Raney-Ni in ethanol affords 7,8-difluoro-2,3-dihydro-3-methyl-4H-benzoxazine (V), which is condensed with diethyl ethoxymethylenemalonate (VI) by heating at 145 C giving the malonic derivative (VII). The cyclization of (VII) by heating at 145 C with ethyl polyphosphate (PPE) yields ethyl 9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylate (VIII), which is hydrolyzed with HCl in refluxing acetic acid affording the corresponding free acid (IX). Finally, this compound is condensed with N-methylpiperazine (X) in DMSO at 110 C.
| 【1】 Hayakawa, I.; Hiramitsu, T.; Tanaka, Y. (Daiichi Pharmaceutical Co., Ltd.); Benzoxazine derivs.. EP 0047005; US 4382892 . |
| 【2】 Serradell, M.N.; Blancafort, P.; Castaner, J.; DL-8280. Drugs Fut 1983, 8, 5, 395. |
| 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) | 30677 | 1,2,3-trifluoro-4-nitrobenzene; 2,3,4-trifluoronitrobenzene | 771-69-7 | C6H2F3NO2 | 详情 | 详情 |
| (II) | 30678 | 2,3-difluoro-6-nitrophenol | 82419-26-9 | C6H3F2NO3 | 详情 | 详情 |
| (III) | 15288 | 1-Chloroacetone; Chloroacetone | 78-95-5 | C3H5ClO | 详情 | 详情 |
| (IV) | 30679 | 1-(2,3-difluoro-6-nitrophenoxy)acetone | C9H7F2NO4 | 详情 | 详情 | |
| (V) | 30680 | 7,8-difluoro-3-methyl-3,4-dihydro-2H-1,4-benzoxazine | C9H9F2NO | 详情 | 详情 | |
| (VI) | 14088 | Diethyl ethoxymethylenemalonate; Diethyl 2-(ethoxymethylene)malonate | 87-13-8 | C10H16O5 | 详情 | 详情 |
| (VII) | 30681 | diethyl 2-[(7,8-difluoro-3-methyl-2,3-dihydro-4H-1,4-benzoxazin-4-yl)methylene]malonate | C17H19F2NO5 | 详情 | 详情 | |
| (VIII) | 30682 | ethyl 9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylate | C15H13F2NO4 | 详情 | 详情 | |
| (IX) | 12058 | 9,10-Difluoro-3-methyl-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid; 8,9-Difluoro-3-me-6-oxo-2,3-dihydro-6h-1-oxa-3a-aza-phenalene-5-carboxylic acid | 82419-35-0 | C13H9F2NO4 | 详情 | 详情 |
| (X) | 10061 | 1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine | 109-01-3 | C5H12N2 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：A new efficient synthesis of 2-acetylbenzothiophene (I), the key starting material for the previously reported synthesis of zileuton, has been described: Thiophenol (II) is dilithiated with butyllithium and tetramethylethylenediamine in cyclohexane to compound (III), which is then cyclized by successive treatments with DMF and chloroacetone (IV) in THF to afford (I) in high yield.
| 【1】 Brooks, D.W.; Basha, A.; Synthesis of the 5-lipoxygenase inhibitor zileuton from thiophenol. J Org Chem 1993, 58, 5, 1293. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 15288 | 1-Chloroacetone; Chloroacetone | 78-95-5 | C3H5ClO | 详情 | 详情 | |
| (I) | 12947 | 1-(1-Benzothiophen-2-yl)-1-ethanone | 22720-75-8 | C10H8OS | 详情 | 详情 |
| (II) | 12951 | Benzenethiol; Phenylmercaptan; Phenylhydrosulfide | 108-98-5 | C6H6S | 详情 | 详情 |
| (III) | 12952 | 2-Lithio-thiophenol lithium salt | C6H4Li2S | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(II)Vamicamide is synthesized by two closely related ways (1). Scheme 1: 1) The alkylation of 2-phenyl-2-(2-pyridyl)acetonitrile (I) with chloroacetone (II) is achieved in the presence of KOH in DMSO to give the 4-oxopentanenitrile derivative (III). Compound (III) is then converted to (V) by reaction with dimethylamine (IV) using titanium tetrachloride and successive reduction with NaBH4. The nitrile (V) (a mixture of two diastereoisomers) is hydrolyzed with concentrated H2SO4 in acetic acid to give the final pentanamide derivative as a racemic mixture of two diastereoisomers, A-racemate and B-racemate. Separation is accomplished by recrystallization of their maleic acid salts. The racemates are resolved by recrystallization with (-)-dibenzoyl-L-tartaric acid. 2) The reaction of 2-phenyl-2-(2-pyridyl)acetonitrile (I) with 2-(dimethylamino)propylchloride (VI) using a base affords the intermediate (V), which is hydrolyzed with concentrated sulfuric acid in acetic acid to give the final pentanamide derivative as a mixture of two diastereoisomers. These are resolved by recrystallization.
| 【1】 Mealy, N.; Castaner, J.; Vamicamide. Drugs Fut 1995, 20, 10, 1018. |
| 【2】 Oyasu, H.; Nagano, M.; Akahane, A.; Tomoi, M.; Tada, T.; Matsuo, M.; Synthesis and anticholinergic activity of the four stereoisomers of 4-(dimethylamino)-2-phenyl-2-(2-pyridyl)pentanamide. J Med Chem 1994, 37, 9, 1378-81. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VI)) | 15290 | N-(2-chloro-1-methylethyl)-N,N-dimethylamine; 1-chloro-N,N-dimethyl-2-propanamine | C5H12ClN | 详情 | 详情 | |
| (I) | 15287 | alpha-phenyl-2-pyridineacetonitrile; 2-phenyl-2-(2-pyridinyl)acetonitrile; 2-Pyridineacetonitrile; Phenyl-2-(2-pyridinyl)acetonitrile | 5005-36-7 | C13H10N2 | 详情 | 详情 |
| (II) | 15288 | 1-Chloroacetone; Chloroacetone | 78-95-5 | C3H5ClO | 详情 | 详情 |
| (III) | 15289 | 4-oxo-2-phenyl-2-(2-pyridinyl)pentanenitrile | C16H14N2O | 详情 | 详情 | |
| (V) | 15291 | 4-(dimethylamino)-2-phenyl-2-(2-pyridinyl)pentanenitrile | C18H21N3 | 详情 | 详情 |
合成路线7
该中间体在本合成路线中的序号：(II)Condensation of 2,6-diamino-4-hydroxypyrimidine (I) with chloroacetone (II) produced a mixture of pyrrolopyrimidine (III) and furopyrimidine (IV). After treatment of this mixture with pivalic anhydride, the insoluble pivaloyl amide of pyrrolopyrimidine (V) was separated from the soluble dipivaloyl furopyrimidine with boiling EtOAc. Subsequent Mannich reaction of (V) with dimethylamine and formaldehyde afforded the (dimethylamino)methyl derivative (VI). The dimethylamino group of (VI) was then displaced with 4-mercaptopyridine (VII) to give thioether (VIII). Finally, the pivaloyl amide group of (VIII) was hydrolyzed with NaOH to yield the target compound.
| 【1】 Gangjee, A.; et al.; 2-Amino-4-oxo-5-substituted-pyrrolo[2,3-d.]pyrimidines as nonclassical antifolate inhibitors of thymidylate synthase. J Med Chem 1996, 39, 23, 4563-4568. |
| 【2】 Gangjee, A.; et al.; Synthesis of classical and a nonclassical 2-amino-4-oxo-6-methyl-5-substituted Pyrrolo[2,3-d]pyrimidine antifolate inhibitors of thymidylate synthase1. J Med Chem 1999, 42, 12, 2272. |
| 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) | 14227 | N-Hydroxy-2-phenyl-4,5-dihydro-1,3-oxazole-4-carboxamide | C10H10N2O3 | 详情 | 详情 | |
| (II) | 15288 | 1-Chloroacetone; Chloroacetone | 78-95-5 | C3H5ClO | 详情 | 详情 |
| (III) | 27932 | 2-amino-6-methyl-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one | C7H8N4O | 详情 | 详情 | |
| (IV) | 27933 | 5-methylfuro[2,3-d]pyrimidine-2,4-diamine | C7H8N4O | 详情 | 详情 | |
| (V) | 27934 | 2,2-dimethyl-N-(6-methyl-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-2-yl)propanamide | C12H16N4O2 | 详情 | 详情 | |
| (VI) | 27935 | N-[5-[(dimethylamino)methyl]-6-methyl-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-2-yl]-2,2-dimethylpropanamide | C15H23N5O2 | 详情 | 详情 | |
| (VII) | 27936 | 4-Mercaptopyridine; 4-pyridinethiol | 4556-23-4 | C5H5NS | 详情 | 详情 |
| (VIII) | 27937 | 2,2-dimethyl-N-[6-methyl-4-oxo-5-[(4-pyridinylsulfanyl)methyl]-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-2-yl]propanamide | C18H21N5O2S | 详情 | 详情 |
合成路线8
该中间体在本合成路线中的序号：(IX)The starting product ethyl 1,4-dimethyl-3-ethoxycarbonylpyrrole-2-acetate (I) can be obtained by condensation of diethyl acetonedicarboxylate (X) with chloroacetone (IX) by means of methylamine in water, the compound (XI) being formed as an intermediate which is not isolated. The Friedel-Crafts aroylation of (I) with p-chlorobenzoyl chloride (B) and AlCl3 in refluxing dichloroethane gives ethyl 5-(p-chlorobenzoyl)-1,4-dimethyl-3-ethoxycarbonylpyrrole-2-acetate (VI), which by hydrolysis with aqueous 1N NaOH yields 5-(p-chlorobenzoyl)-1,4-dimethyl-3-carboxypyrrole-2-acetic acid (VII). The partial esterification of (VII) with ethanol and HCl produces ethyl 5-(p-chlorobenzoyl)-1,4-dimethyl-3-carboxypyrrole-2-acetate (VIII), which by decarboxylation at 210-30 C is converted into the ester (V) already obtained.
| 【1】 Carson, J.R.; Aroyl-substituted pyrroles. DE 2102746; FR 2081455; GB 1327308; JP 55033401; JP 55033402; US 3752826; US 3865840; US 4070368 . |
| 【2】 Hillier, K.; Castañer, J.; Zomepirac. Drugs Fut 1977, 2, 10, 698. |
| 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) | 10295 | p-Chlorobenzoyl chloride; 4-Chlorobenzoyl chloride | 122-01-0 | C7H4Cl2O | 详情 | 详情 |
| (I) | 40135 | ethyl 2-(2-ethoxy-2-oxoethyl)-1,4-dimethyl-1H-pyrrole-3-carboxylate | C13H19NO4 | 详情 | 详情 | |
| (V) | 40140 | ethyl 2-[5-(4-chlorobenzoyl)-1,4-dimethyl-1H-pyrrol-2-yl]acetate | C17H18ClNO3 | 详情 | 详情 | |
| (VI) | 40143 | ethyl 5-(4-chlorobenzoyl)-2-(2-ethoxy-2-oxoethyl)-1,4-dimethyl-1H-pyrrole-3-carboxylate | C20H22ClNO5 | 详情 | 详情 | |
| (VII) | 40144 | 2-(carboxymethyl)-5-(4-chlorobenzoyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid | C16H14ClNO5 | 详情 | 详情 | |
| (VIII) | 40145 | 5-(4-chlorobenzoyl)-2-(2-ethoxy-2-oxoethyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid | C18H18ClNO5 | 详情 | 详情 | |
| (IX) | 15288 | 1-Chloroacetone; Chloroacetone | 78-95-5 | C3H5ClO | 详情 | 详情 |
| (X) | 40141 | diethyl 3-oxopentanedioate | 105-50-0 | C9H14O5 | 详情 | 详情 |
| (XI) | 40142 | methanaminium 1-chloro-6-ethoxy-3-(ethoxycarbonyl)-2-methyl-4,6-dioxo-2-hexanolate | C13H24ClNO6 | 详情 | 详情 |
合成路线9
该中间体在本合成路线中的序号：(VI)Alkylation of 2,4-dinitrothiophenol (I) with 2-bromoisobutyrate (II) and K2CO3 in DMF yields thioether (III), which is then subjected to reduction with Fe/HCl in EtOH/H2O, followed by ring closure with refluxing NaOH, to give benzothiazine derivative (IV). Conversion of amino compound (IV) into nitro derivative (V) is then performed via Sandmeyer reaction by first treatment with NaNO2/H2SO4 in H2O, followed by reaction with NaHCO3, NaNO2, CuSO4 and Cu2O in H2O. N-Alkylation of (V) with chloroacetone (VI) and K2CO3 in DMF provides (VII), which is finally converted into the target compound by reduction with BH3-THF complex in THF, followed by Swern oxidation with DMSO and oxalyl chloride in CH2Cl2.
| 【1】 Yoden, T.; Matsuhisa, A.; Yamagiwa, Y.; Nohira, H.; Tsuzuki, R.; Yanagisawa, I.; Matsumoto, Y.; Shibanuma, T.; Novel potassium channel openers. Part 4: Transformation of the 1,4-benzoxazine skeleton into 1,4-benzothiazine, 1,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydroquinoxaline, indoline, and 1,5-benzoxazepine. Bioorg Med Chem 2000, 8, 2, 393. |
| 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) | 45972 | 2,4-dinitrobenzenethiol; 2,4-dinitrophenylhydrosulfide | C6H4N2O4S | 详情 | 详情 | |
| (II) | 39799 | ethyl 2-bromo-2-methylpropanoate | 600-00-0 | C6H11BrO2 | 详情 | 详情 |
| (III) | 45973 | ethyl 2-[(2,4-dinitrophenyl)sulfanyl]-2-methylpropanoate | C12H14N2O6S | 详情 | 详情 | |
| (IV) | 45974 | 6-amino-2,2-dimethyl-2H-1,4-benzothiazin-3(4H)-one | C10H12N2OS | 详情 | 详情 | |
| (V) | 45975 | 2,2-dimethyl-6-nitro-2H-1,4-benzothiazin-3(4H)-one | C10H10N2O3S | 详情 | 详情 | |
| (VI) | 15288 | 1-Chloroacetone; Chloroacetone | 78-95-5 | C3H5ClO | 详情 | 详情 |
| (VII) | 45976 | 2,2-dimethyl-6-nitro-4-(2-oxopropyl)-2H-1,4-benzothiazin-3(4H)-one | C13H14N2O4S | 详情 | 详情 |
合成路线10
该中间体在本合成路线中的序号：(VI)The condensation of 2-(4-bromophenyl)acetic acid methyl ester (I) with 2-(trimethylstannyl)pyridine (II) by means of Pd(PPh3)4 in refluxing toluene gives 2-[4-(2-pyridyl)phenyl]acetic acid methyl ester (III), which is hydrolyzed with KOH in THF/water to yield the corresponding acetic acid (IV). Finally, this compound is condensed with 4-methyl-2-(methylamino)thiazole-5-sulfonamide (V) by means of HOBt and DEC in DMF to afford the target phenylacetamide. The intermediate 4-methyl-2-(methylamino)thiazole-5-sulfonamide (V) is obtained as follows: the reaction of 1-chloroacetone (VI) with KSCN in water gives the corresponding thiocyanato (VII), which is cyclized by means of dry HCl in dichloromethane to yield 2-chloro-4-methylthiazole (VIII). The reaction of (VIII) with Cl-SO3H and SOCl2 affords the sulfonyl chloride (IX), which is treated with ammonia in THF/water to provide 2-chloro-4-methylthiazole-5-sulfonamide (X). Finally, this compound is treated with methylamine in acetonitrile to obtain the target sulfonamide intermediate (V).
| 【1】 Fischer, R.; Bender, W.; Henninger, K.; Eckenberg, P.; Handke, G.; Keldenich, J.; Weber, O.; Kleymann, G.; Betz, U.; Hendrix, M.; Schneider, U.; Jensen, A.; Baumeister, J. (Bayer AG); Thiazolyl amide derivs.. DE 19962532; WO 0147904 . |
| 【2】 Fischer, R.; Bender, W.; Henninger, K.; Eckenberg, P.; Handke, G.; Keldenich, J.; Weber, O.; Kleymann, G.; Betz, U.; Hendrix, M.; Schneider, U.; Jensen, A.; Baumeister, J.; Hewlett, G.; Pevzner, V. (Bayer AG); Incompetitive inhibitors of helicase primase. DE 10044353; WO 0220014 . |
| 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) | 16992 | methyl 2-(4-bromophenyl)acetate | 41841-16-1 | C9H9BrO2 | 详情 | 详情 |
| (II) | 55389 | 2-Pyridyltrimethyltin; Trimethyl(2-pyridyl)tin | 13737-05-8 | C8H13NSn | 详情 | 详情 |
| (III) | 55390 | methyl 2-[4-(2-pyridinyl)phenyl]acetate | C14H13NO2 | 详情 | 详情 | |
| (IV) | 55391 | 2-[4-(2-pyridinyl)phenyl]acetic acid | C13H11NO2 | 详情 | 详情 | |
| (V) | 55392 | 4-methyl-2-(methylamino)-1,3-thiazole-5-sulfonamide | C5H9N3O2S2 | 详情 | 详情 | |
| (VI) | 15288 | 1-Chloroacetone; Chloroacetone | 78-95-5 | C3H5ClO | 详情 | 详情 |
| (VII) | 55393 | 2-oxo-1-propanesulfenyl cyanide | C4H5NOS | 详情 | 详情 | |
| (VIII) | 55394 | 2-chloro-4-methyl-1,3-thiazole | C4H4ClNS | 详情 | 详情 | |
| (IX) | 55395 | 2-chloro-4-methyl-1,3-thiazole-5-sulfonyl chloride | C4H3Cl2NO2S2 | 详情 | 详情 | |
| (X) | 55396 | 2-chloro-4-methyl-1,3-thiazole-5-sulfonamide | C4H5ClN2O2S2 | 详情 | 详情 |
合成路线11
该中间体在本合成路线中的序号：(V)Condensation of 4-methyl-7-hydroxypyrano[2,3-b]pyridin-2-one (I) with N,N-dimethylthiocarbamoyl chloride gives the thiocarbamate (II), which undergoes thermal rearrangement at 220 C to the S-aryl thiocarbamate isomer (III). Subsequent alkaline hydrolysis of (III) provides the 7-mercapto azacoumarin (IV). Alkylation of (IV) with chloroacetone (V) affords thioether (VI). This compound is finally cyclized to the target pyranothienopyridine compound under alkaline conditions.
| 【1】 Via, L.D.; et al.; Synthesis, photobiological activity and photoreactivity of methyl-thieno-8-azacoumarins, novel bioisosters of psoralen. Bioorg Med Chem Lett 2002, 12, 9, 1253. |
| 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) | 58431 | 7-hydroxy-4-methyl-2H-pyrano[2,3-b]pyridin-2-one | C9H7NO3 | 详情 | 详情 | |
| (II) | 58432 | O-(4-methyl-2-oxo-2H-pyrano[2,3-b]pyridin-7-yl) dimethylcarbamothioate | C12H12N2O3S | 详情 | 详情 | |
| (III) | 58433 | S-(4-methyl-2-oxo-2H-pyrano[2,3-b]pyridin-7-yl) dimethylcarbamothioate | C12H12N2O3S | 详情 | 详情 | |
| (IV) | 58434 | 4-methyl-7-sulfanyl-2H-pyrano[2,3-b]pyridin-2-one | C9H7NO2S | 详情 | 详情 | |
| (V) | 15288 | 1-Chloroacetone; Chloroacetone | 78-95-5 | C3H5ClO | 详情 | 详情 |
| (VI) | 58435 | 4-methyl-7-[(2-oxopropyl)sulfanyl]-2H-pyrano[2,3-b]pyridin-2-one | C12H11NO3S | 详情 | 详情 |