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【结 构 式】 
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【分子编号】52080 【品名】2-(4-morpholinyl)malononitrile 【CA登记号】 |
【 分 子 式 】C7H9N3O 【 分 子 量 】151.16808 【元素组成】C 55.62% H 6% N 27.8% O 10.58% |
合成路线1
该中间体在本合成路线中的序号：(X)The condensation between 2-fluorobenzylhydrazine (I) and the sodium enolate of ethyl cyanopyruvate (II) in the presence of trifluoroacetic acid produced the pyrazole derivative (III). Subsequent cyclization of aminopyrazole (III) with (dimethylamino)acrolein (IV) gave the pyrazolopyridine (V). Amonolysis of the ethyl ester group of (V) afforded amide (VI), which was further dehydrated to nitrile (VII) by means of trifluoroacetic anhydride and pyridine. Addition of sodium methoxide to nitrile (VII) furnished imidate (VIII). This was converted to the corresponding amidine (IX) upon treatment with ammonium chloride and HOAc. Finally, the title diamino pyrimidine compound was obtained by heating a mixture of amidine (IX) and morpholinomalononitrile (X).
| 【1】 Feurer, A.; et al.; 3-(2-Pyrimidinyl)pyrazolo[3,4-b]pyridines: A novel class of orally active NO-independent stimulators of soluble guanylate cyclase. 222nd ACS Natl Meet (Aug 26 2001, Chicago) 2001, Abst MEDI 205. |
| 【2】 Hutter, J.; Stasch, J.-P.; Dembowsky, K.; Perzborn, E.; Straub, A.; Feurer, A.; Alonso-Alija, C.; Stahl, E. (Bayer AG); Substd. pyrazolo derivs. condensed with six-membered heterocyclic rings. DE 19834044; EP 1102768; WO 0006569 . |
| 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) | 50471 | 1-(2-fluorobenzyl)hydrazine | 51859-98-4 | C7H9FN2 | 详情 | 详情 |
| (II) | 52079 | sodium (Z)-1-cyano-3-ethoxy-3-oxo-1-propen-2-olate | 627076-29-3 | C6H6NNaO3 | 详情 | 详情 |
| (III) | 50472 | ethyl 5-amino-1-(2-fluorobenzyl)-1H-pyrazole-3-carboxylate | 256504-39-9 | C13H14FN3O2 | 详情 | 详情 |
| (IV) | 11789 | (E)-3-(Dimethylamino)-2-propenal | 692-32-0 | C5H9NO | 详情 | 详情 |
| (V) | 50473 | ethyl 1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboxylate | 256376-59-7 | C16H14FN3O2 | 详情 | 详情 |
| (VI) | 50474 | 1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboxamide | 256376-62-2 | C14H11FN4O | 详情 | 详情 |
| (VII) | 50475 | 1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile | 256376-65-5 | C14H9FN4 | 详情 | 详情 |
| (VIII) | 50476 | methyl 1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboximidoate | 304874-06-4 | C15H13FN4O | 详情 | 详情 |
| (IX) | 50477 | 1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboximidamide | 256376-68-8 | C14H12FN5 | 详情 | 详情 |
| (X) | 52080 | 2-(4-morpholinyl)malononitrile | C7H9N3O | 详情 | 详情 |