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【结 构 式】 
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【分子编号】40931 【品名】3-(cyanomethyl)-1-pyridiniumolate 【CA登记号】 |
【 分 子 式 】C7H6N2O 【 分 子 量 】134.13752 【元素组成】C 62.68% H 4.51% N 20.88% O 11.93% |
合成路线1
该中间体在本合成路线中的序号：(I)Reaction of 3-(cyanomethyl)pyridine-N-oxide (I) with cyanotrimethylsilane and dimethylcarbamoyl chloride provided dinitrile (II). Subsequent cyclization of (II) in the presence of HBr gave rise to 6-amino-8-bromo-1,7-naphthyridine (III). Attachment of a 3-nitrophenyl group to (III) to afford (V) was carried out by Suzuki coupling of (III) with 3-nitrophenylboronic acid (IV) in the presence of bis(dibenzylideneacetone)palladium and triphenylphosphine. The required triflate (VI) was then obtained by nitrosation of aminonaphthyridine (V) in trifluromethanesulfonic acid/DMF. Finally, a second Suzuki coupling of (VI) with 4-carboxyphenylboronic acid (VII) provided the title 6,8-diarylnaphthyridine.
| 【1】 Bray-French, K.; Hersperger, R.; Müller, T.; Mazzoni, L.; Palladium-catalyzed cross-coupling reactions for the synthesis of 6,8-disubstituted 1,7-naphthyridines: A novel class of potent and selective phosphodiesterase type 4D inhibitors. J Med Chem 2000, 43, 4, 675. |
| 【2】 Hersperger, R. (Novartis AG); Naphtyridine derivs.. EP 0934320; US 6136821; WO 9818796 . |
| 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) | 40931 | 3-(cyanomethyl)-1-pyridiniumolate | C7H6N2O | 详情 | 详情 | |
| (II) | 40932 | 3-(cyanomethyl)-2-pyridinecarbonitrile | C8H5N3 | 详情 | 详情 | |
| (III) | 40933 | 8-bromo[1,7]naphthyridin-6-ylamine; 8-bromo[1,7]naphthyridin-6-amine | C8H6BrN3 | 详情 | 详情 | |
| (IV) | 40934 | 3-nitrophenylboronic acid | 13331-27-6 | C6H6BNO4 | 详情 | 详情 |
| (V) | 40935 | 8-(3-nitrophenyl)[1,7]naphthyridin-6-ylamine; 8-(3-nitrophenyl)[1,7]naphthyridin-6-amine | C14H10N4O2 | 详情 | 详情 | |
| (VI) | 40936 | 8-(3-nitrophenyl)[1,7]naphthyridin-6-yl trifluoromethanesulfonate | C15H8F3N3O5S | 详情 | 详情 | |
| (VII) | 32841 | 4-(dihydroxyboryl)benzoic acid；4-Boronobenzoic acid；4-carboxyphenylboronic acid;4-(Dihydroxyboryl)benzoic acid | 14047-29-1 | C7H7BO4 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VI)3-(Cyanomethyl)pyridine-N-oxide (VI) was converted to the pyridine dinitrile (VII) by treatment with cyanotrimethylsilane and dimethylcarbamoyl chloride. Cyclization of dinitrile (VII) in the presence of HBr gave rise to 6-amino-8-bromo-1,7-naphthyridine (VIII). Attachment of the benzofurazanyl moiety to (VIII) was performed by Suzuki coupling with boronic acid (V) in the presence of bis(dibenzylideneacetone)palladium and tri(o-tolyl)phosphine. The resultant 6 amino-8-aryl naphthyridine (IX) was subjected to diazotization in the presence of trifluoromethanesulfonic acid to furnish triflate (X). Further Suzuki coupling of triflate (X) with 4-carboxyphenylboronic acid (XI) led to the title compound.
| 【1】 Hersperger, R.; Dawson, J.; Mueller, T.; Synthesis of 4-(8-benzo[1,2,5]oxadiazol-5-yl-[1,7]naphthyridine-6-yl)-benzoic acid: A potent and selective phosphodiesterase type 4D inhibitor. Bioorg Med Chem Lett 2002, 12, 2, 233. |
| 【2】 Hersperger, R. (Novartis AG); Naphtyridine derivs.. EP 0934320; US 6136821; WO 9818796 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (V) | 59799 | 2,1,3-benzoxadiazol-5-ylboronic acid | C6H5BN2O3 | 详情 | 详情 | |
| (VI) | 40931 | 3-(cyanomethyl)-1-pyridiniumolate | C7H6N2O | 详情 | 详情 | |
| (VII) | 40932 | 3-(cyanomethyl)-2-pyridinecarbonitrile | C8H5N3 | 详情 | 详情 | |
| (VIII) | 40933 | 8-bromo[1,7]naphthyridin-6-ylamine; 8-bromo[1,7]naphthyridin-6-amine | C8H6BrN3 | 详情 | 详情 | |
| (IX) | 59906 | 8-(2,1,3-benzoxadiazol-5-yl)[1,7]naphthyridin-6-amine; 8-(2,1,3-benzoxadiazol-5-yl)[1,7]naphthyridin-6-ylamine | C14H9N5O | 详情 | 详情 | |
| (X) | 59907 | 8-(2,1,3-benzoxadiazol-5-yl)[1,7]naphthyridin-6-yl trifluoromethanesulfonate | C15H7F3N4O4S | 详情 | 详情 | |
| (XI) | 32841 | 4-(dihydroxyboryl)benzoic acid；4-Boronobenzoic acid；4-carboxyphenylboronic acid;4-(Dihydroxyboryl)benzoic acid | 14047-29-1 | C7H7BO4 | 详情 | 详情 |