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【结 构 式】

【分子编号】29488

【品名】(E)-3-(4-methylphenyl)-2-propenoyl azide

【CA登记号】

【 分 子 式 】C10H9N3O

【 分 子 量 】187.20108

【元素组成】C 64.16% H 4.85% N 22.45% O 8.55%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(II)

The reaction of 3-(4-methylphenyl)-2-propenoic acid (I) with ethyl chloroformate or with SOCl2 and then with sodium azide gives the corresponding azide (II), which is cyclized termally yielding 7-methylisoquinolin-1(2H)-one (III). The reaction of (III) with refluxing POCl3 affords 1-chloro-7-methylisoquinoline (IV), which is brominated with NBS and benzoyl peroxide in refluxing CCl4 giving the bromomethyl derivative (V). The condensation of (V) with 3(S)-(tert-butoxycarbonylamino)pyrrolidin-2-one (VI) (obtained by cyclization of the diaminobutyric acid (VII) by means of HOBT in THF) by means of NaH in THF/DMF yields the N-substituted pyrrolidone (VIII), which is deprotected with HCl affording the 3(S)-aminopyrrolidone (IX). The acylation of (IX) with thieno [3,2-b]pyridine-2-sulfonyl chloride (X) by means of triethylamine in acetonitrile gives the sulfonamide (XI), which is finally treated with ammonium acetate in hot phenol. The intermediate sulfonyl chloride (X) has been obtained as follows: The reaction of 2-ethynylpyridine (XII) with benzylthiol and sodium ethoxide in ethanol gives 2-[2-(benzylsulfanyl)vinyl]pyridine (XIII), which is cyclized at 625 C yielding thieno[3,2-bpyridine (XIV). Finally, this compound is chlorosulfonated by reaction with BuLi, SO2 and SO2Cl2 in THF.

1 Guo, L.; Pan, Y.; Rohrer, S.; Schaeffer, J.; patchett, A.A.; Mosley, R.; Yang, L.; Pastemak, A.; Birzin, E.; 2,4-Bis(aminomethyl)pyridine derived highly potent and selective human somatostatin receptor subtype-2 (hsst2) agonists. 217th ACS Natl Meet (March 21 1999, Anaheim) 1999, Abst MEDI 141.
2 Choi-Sledeski, Y.M.; Pauls, H.W.; Green, D.M.; Barton, J.N.; Becker, M.R.; Ewing, W.R. (Aventis Pharmaceuticals, Inc.); Sulfonic acid or sulfonylamino N-(heteroaralkyl)-azaheterocyclylamide cpds.. EP 0944386; WO 9825611 .
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) 29487 (E)-3-(4-methylphenyl)-2-propenoic acid 1866-39-3 C10H10O2 详情 详情
(II) 29488 (E)-3-(4-methylphenyl)-2-propenoyl azide C10H9N3O 详情 详情
(III) 29489 7-methyl-1(2H)-isoquinolinone C10H9NO 详情 详情
(IV) 29490 1-chloro-7-methylisoquinoline C10H8ClN 详情 详情
(V) 29491 7-(bromomethyl)-1-chloroisoquinoline C10H7BrClN 详情 详情
(VI) 29492 tert-butyl (3S)-2-oxopyrrolidinylcarbamate C9H16N2O3 详情 详情
(VII) 29493 (2S)-4-amino-2-[(tert-butoxycarbonyl)amino]butyric acid C9H18N2O4 详情 详情
(VIII) 29494 tert-butyl (3S)-1-[(1-chloro-7-isoquinolinyl)methyl]-2-oxopyrrolidinylcarbamate C19H22ClN3O3 详情 详情
(IX) 29495 (3S)-3-amino-1-[(1-chloro-7-isoquinolinyl)methyl]-2-pyrrolidinone C14H14ClN3O 详情 详情
(X) 29496 thieno[3,2-b]pyridine-2-sulfonyl chloride C7H4ClNO2S2 详情 详情
(XI) 29497 N-[(3S)-1-[(1-chloro-7-isoquinolinyl)methyl]-2-oxopyrrolidinyl]thieno[3,2-b]pyridine-2-sulfonamide C21H17ClN4O3S2 详情 详情
(XII) 29498 2-ethynylpyridine 1945-84-2 C7H5N 详情 详情
(XIII) 29499 benzyl (Z)-2-(2-pyridinyl)ethenyl sulfide; 2-[(Z)-2-(benzylsulfanyl)ethenyl]pyridine C14H13NS 详情 详情
(XIV) 29500 thieno[3,2-b]pyridine C7H5NS 详情 详情
Extended Information