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【结 构 式】 
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【分子编号】28662 【品名】3-aminobenzonitrile 【CA登记号】2237-30-1 |
【 分 子 式 】C7H6N2 【 分 子 量 】118.13812 【元素组成】C 71.17% H 5.12% N 23.71% |
合成路线1
该中间体在本合成路线中的序号：(I)The sulfonation of 3-aminobenzonitrile (I) with benzenesulfonyl chloride (II) by means of triethylamine in dichloromethane gives the sulfonamide (III), which is nitrated with HNO3 in acetic anhydride yielding 4-nitro-3-(phenyl sulfonamido)benzonitrile (IV). The reduction of (IV) with SnCl2 in hot ethanol affords the corresponding 4-amino derivative (V), which is finally condensed with 2-bromophenyl isocyanate (VI) in hot DMF.
| 【1】 Widdowson, K.L.; Veber, D.F.; Jurewicz, A.J.; Rutledge, M.C. Jr.; Hertzberg, R.P. (SmithKline Beecham plc); IL-8 receptor antagonists. EP 0809492; JP 1999503110; US 5780483; WO 9625157 . |
| 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) | 28662 | 3-aminobenzonitrile | 2237-30-1 | C7H6N2 | 详情 | 详情 |
| (II) | 14713 | benzenesulfonyl chloride | 98-09-9 | C6H5ClO2S | 详情 | 详情 |
| (III) | 28663 | N-(3-cyanophenyl)benzenesulfonamide | C13H10N2O2S | 详情 | 详情 | |
| (IV) | 28664 | N-(5-cyano-2-nitrophenyl)benzenesulfonamide | C13H9N3O4S | 详情 | 详情 | |
| (V) | 28665 | N-(2-amino-5-cyanophenyl)benzenesulfonamide | C13H11N3O2S | 详情 | 详情 | |
| (VI) | 28666 | 1-bromo-2-isocyanatobenzene | 1592-00-3 | C7H4BrNO | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)The sulfonation of 3-aminobenzonitrile (I) with benzenesulfonyl chloride (II) by means of triethylamine in dichloromethane gives the sulfonamide (III), which is nitrated with HNO3 in acetic anhydride yielding 4-nitro-3-(phenyl sulfonamido)benzonitrile (IV). The reduction of (IV) with SnCl2 in hot ethanol affords the corresponding 4-amino derivative (V), which is finally condensed with 2,3-dichlorophenyl isocyanate (VI) in hot DMF.
| 【1】 Widdowson, K.L.; Veber, D.F.; Jurewicz, A.J.; Rutledge, M.C. Jr.; Hertzberg, R.P. (SmithKline Beecham plc); IL-8 receptor antagonists. EP 0809492; JP 1999503110; US 5780483; WO 9625157 . |
| 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) | 28662 | 3-aminobenzonitrile | 2237-30-1 | C7H6N2 | 详情 | 详情 |
| (II) | 14713 | benzenesulfonyl chloride | 98-09-9 | C6H5ClO2S | 详情 | 详情 |
| (III) | 28663 | N-(3-cyanophenyl)benzenesulfonamide | C13H10N2O2S | 详情 | 详情 | |
| (IV) | 28664 | N-(5-cyano-2-nitrophenyl)benzenesulfonamide | C13H9N3O4S | 详情 | 详情 | |
| (V) | 28665 | N-(2-amino-5-cyanophenyl)benzenesulfonamide | C13H11N3O2S | 详情 | 详情 | |
| (VI) | 28667 | 1,2-dichloro-3-isocyanatobenzene | 41195-90-8 | C7H3Cl2NO | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(XVII)Synthesis of EN 287632: 3-Cyanoaniline (XVII) is converted into 3-cyanobenzenesulfonyl chloride (XVIII) by first treatment with NaNO2 in H2O/HCl followed by reaction with HOAc saturated with SO2 and CuCl. To obtain the final compound, sulfonyl chloride derivative (XVIII) is condensed with intermediate (VIII) by means of pyridine in THF.
| 【1】 Kamata, J.; Semba, T.; Nara, K.; Ohwa, T.; Hata, N.; Haneda, T.; Funahashi, Y.; Hamaoka, S.; Tsuruoka, A.; Ueda, N.; Wakabayashi, T.; Ozawa, Y.; Yamamoto, Y.; Okabe, T.; Takahashi, K.; Tsukahara, N. (Eisai Co., Ltd.); Sulfonamide-containing indole cpds.. EP 1074542; JP 2000247949; WO 0050395 . |
合成路线4
该中间体在本合成路线中的序号：(II)Condensation between dichloropurine (I) and substituted aniline (II) in pentanol affords derivative (III), which is then alkylated with ethyl iodide (IV) by means of Cs2CO3 in DMF to provide purine (V). Finally, the desired compound is obtained by attack of amine (VI) and displacement of the chlorine atom of derivative (V) in diglyme.
| 【1】 Bruggen, J.; Caravatti, G.; Capraro, H.-G.; et al.; Chemistry and biological characterization of CGP79807, a highly selective CDK1/2 inhibitor. 221st ACS Natl Meet (April 1 2001, San Diego) 2001, Abst MEDI 150. |
| 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) | 25254 | 2,6-dichloro-9H-purine | 5451-40-1 | C5H2Cl2N4 | 详情 | 详情 |
| (II) | 28662 | 3-aminobenzonitrile | 2237-30-1 | C7H6N2 | 详情 | 详情 |
| (III) | 48922 | 3-[(2-chloro-9H-purin-6-yl)amino]benzonitrile | C12H7ClN6 | 详情 | 详情 | |
| (IV) | 10925 | Iodoethane;ethyl iod | 75-03-6 | C2H5I | 详情 | 详情 |
| (V) | 48923 | 3-[(2-chloro-9-ethyl-9H-purin-6-yl)amino]benzonitrile | C14H11ClN6 | 详情 | 详情 | |
| (VI) | 19581 | trans-4-Aminocyclohexanol；trans-4-Amino-1-cyclohexanol;trans-4-Amino-1-cyclohexanol; | 27489-62-9 | C6H13NO | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(II)Condensation of chloropyrimidinone (I) with 3-aminobenzonitrile (II) produces the anilino pyrimidinone (III). This is subsequently chlorinated to chloropyrimidine (IV) by using phosphoryl chloride in the presence of N,N-dimethylaniline and tetraethylammonium chloride. Reduction of the nitro group of (IV) to amine (V) is performed by means of stannous chloride and sodium borohydride. Condensation of diaminopyrimidine (V) with 3-fluorobenzaldehyde (VI), followed by oxidative treatment with ferric chloride, furnishes the purine derivative (VII). Conversion of aminopurine (VII) to the iodo analogue (VIII) is achieved by diazotization with isoamyl nitrite in the presence of cuprous iodide and diiodomethane. Iodopurine (VIII) is then coupled to 1-ethynylcyclohexanol (IX) in the presence of palladium catalyst to give the disubstituted alkyne (X).
| 【1】 Asano, O.; Kawata, T.; Inoue, T.; Horizoe, T.; Yasuda, N.; Nagata, K.; Nagaoka, J.; Kobayashi, S.; Tanaka, I.; Abe, S.; Harada, H.; Murakami, M.; 2-Alkynyl-8-aryladenines possessing an amide moiety: Their synthesis and structure-activity relationships of effects on hepatic glucose production induced via agonism of the A2B adenosine receptor. Bioorg Med Chem 2001, 9, 10, 2709. |
| 【2】 Asano, O.; Hoshino, Y.; Kobayashi, S.; Nagata, K.; Harada, H.; Yoshikawa, S.; Nagaoka, J.; Inoue, T.; Horizoe, T.; Yasuda, N.; Murakami, M. (Eisai Co., Ltd.); Purine derivs. and adenosine A2 receptor antagonists serving as preventives/remedies for diabetes. EP 1054012; JP 1999263789; WO 9935147 . |
| 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) | 57619 | N-(4-chloro-5-nitro-6-oxo-1,6-dihydro-2-pyrimidinyl)acetamide | C6H5ClN4O4 | 详情 | 详情 | |
| (II) | 28662 | 3-aminobenzonitrile | 2237-30-1 | C7H6N2 | 详情 | 详情 |
| (III) | 57620 | N-[4-(3-cyanoanilino)-5-nitro-6-oxo-1,6-dihydro-2-pyrimidinyl]acetamide | C13H10N6O4 | 详情 | 详情 | |
| (IV) | 57621 | N-[4-chloro-6-(3-cyanoanilino)-5-nitro-2-pyrimidinyl]acetamide | C13H9ClN6O3 | 详情 | 详情 | |
| (V) | 57622 | 3-[(2,5-diamino-6-chloro-4-pyrimidinyl)amino]benzonitrile | C11H9ClN6 | 详情 | 详情 | |
| (VI) | 18887 | 3-Fluorobenzaldehyde | 456-48-4 | C7H5FO | 详情 | 详情 |
| (VII) | 57623 | 3-[2-amino-6-chloro-8-(3-fluorophenyl)-9H-purin-9-yl]benzonitrile | C18H10ClFN6 | 详情 | 详情 | |
| (VIII) | 57624 | 3-[6-chloro-8-(3-fluorophenyl)-2-iodo-9H-purin-9-yl]benzonitrile | C18H8ClFIN5 | 详情 | 详情 | |
| (IX) | 57625 | 1-ethynylcyclohexanol | C8H12O | 详情 | 详情 | |
| (X) | 57626 | 3-{6-chloro-8-(3-fluorophenyl)-2-[2-(1-hydroxycyclohexyl)ethynyl]-9H-purin-9-yl}benzonitrile | C26H19ClFN5O | 详情 | 详情 |