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【结 构 式】 
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【分子编号】12035 【品名】4-chlorophenyl isocyanate; 1-Chloro-4-isocyanatobenzene; p-Chlorophenyl isocyanate 【CA登记号】104-12-1 |
【 分 子 式 】C7H4ClNO 【 分 子 量 】153.5676 【元素组成】C 54.75% H 2.63% Cl 23.09% N 9.12% O 10.42% |
合成路线1
该中间体在本合成路线中的序号：(IV)1) 5-Indansulfonamide (I) is converted to ethyl N-(5-indansulfonyl)carbamate (II) with ethyl chloroformate and potassium carbonate in refluxing 2-butanone, which is then reacted with 4-chloroaniline (III) in toluene at reflux to provide sulofenur. 2) Alternatively, (I) can be converted to its anion with NaOH in aqueous acetone, then reacted with 4-chlorophenylisocyanate (IV) to give sulofenur directly.
| 【1】 Grindey, G.B.; Indentification of diarylsulfonylureas as novel anticancer drugs. Proc Amer Assoc Cancer Res 1988, 29, 553-6. |
| 【2】 Grossman, C.S.; Kramer, K.E.; Crowell, T.A.; Grindey, G.B.; Rieder, B.J.; Rinzel, S.M.; Harper, R.W.; Howbert, J.J.; Tao, E.V.; Aikins, J.; Shaw, W.N.; Poore, G.A.; Todd, G.C.; Novel agents effective against solid tumors: The diarylsulfonylureas. Synthesis, activities and analysis of quantitative structure-activity relationships. J Med Chem 1990, 33, 9, 2393-407. |
| 【3】 Howbert, J.J.; Sulofenur. Drugs Fut 1991, 16, 6, 517. |
| 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) | 12032 | 5-Indanesulfonamide | 35203-93-1 | C9H11NO2S | 详情 | 详情 |
| (II) | 12033 | ethyl N-(2,3-dihydro-1H-inden-5-ylsulfonyl)carbamate | C12H15NO4S | 详情 | 详情 | |
| (III) | 12034 | 4-Chlorophenylamine; 4-Chloroaniline; p-Chloroaniline | 106-47-8 | C6H6ClN | 详情 | 详情 |
| (IV) | 12035 | 4-chlorophenyl isocyanate; 1-Chloro-4-isocyanatobenzene; p-Chlorophenyl isocyanate | 104-12-1 | C7H4ClNO | 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 target piperazine-1-carboxamide has been obtained by several different methods: 1.- The condensation of 6,7-dimethoxy-4-(1-piperazinyl)quinazoline (I) with 4-chlorophenyl isocyanate (II) in DMF gives the target compound. 2.- The condensation of 6,7-dimethoxy-4-(1-piperazinyl)quinazoline (I) with 4-chlorophenylamine (III) by means of CDI or triphosgene also gives the target piperazine-1-carboxamide. 3.- The reaction of 4-chlorophenylamine (III) with 4-nitrophenyl chloroformate (IV) by means of TEA gives the carbamate (V), which is finally condensed with the quinazoline (I) in hot NMP to yield the target piperazine-1-carboxamide.
| 【1】 Matsuno, K.; Ichimura, M.; Nakajima, T.; Tahara, K.; Fujiwara, S.; Kase, H.; Ushiki, J.; Giese, N.A.; Pandey, A.; Scarborough, R.M.; Lokker, N.A.; Yu, J.C.; Irie, J.; Tsukuda, E.; Ide, S.-i; Oda, S.; Nomoto, Y.; Potent and selective inhibitors of platelet-derived growth factor receptor phosphorylation. 1. Synthesis, structure-activity relationship, and biological effects of a new class of quinazoline derivatives. J Med Chem 2002, 45, 14, 3057. |
| 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) | 41610 | 6,7-dimethoxy-4-(1-piperazinyl)quinazoline; 6-methoxy-4-(1-piperazinyl)-7-quinazolinyl methyl ether | C14H18N4O2 | 详情 | 详情 | |
| (II) | 12035 | 4-chlorophenyl isocyanate; 1-Chloro-4-isocyanatobenzene; p-Chlorophenyl isocyanate | 104-12-1 | C7H4ClNO | 详情 | 详情 |
| (III) | 12034 | 4-Chlorophenylamine; 4-Chloroaniline; p-Chloroaniline | 106-47-8 | C6H6ClN | 详情 | 详情 |
| (IV) | 16605 | 4-Nitrophenyl chloroformate; 1-[(Chlorocarbonyl)oxy]-4-nitrobenzene | 7693-46-1 | C7H4ClNO4 | 详情 | 详情 |
| (V) | 63171 | 4-nitrophenyl 4-chlorophenylcarbamate | C13H9ClN2O4 | 详情 | 详情 |