【结 构 式】 |
【分子编号】25828 【品名】3-methoxy-2-nitrobenzoyl chloride 【CA登记号】 |
【 分 子 式 】C8H6ClNO4 【 分 子 量 】215.59268 【元素组成】C 44.57% H 2.81% Cl 16.44% N 6.5% O 29.68% |
合成路线1
该中间体在本合成路线中的序号:(III)In an alternative procedure, 3-methoxy-2-nitrobenzoic acid (II) was treated with SOCl2 in the presence of DMF in THF, and the resulting acid chloride (III) was converted to amide (IV) with aqueous ammonia. Catalytic hydrogenation of (IV) over Pd/C produced aniline (V), which was then acetylated with AcCl and pyridine. The crude acetylamino compound (VI) was cyclized by treatment with aqueous NaOH to yield the quinazolinone (VII). Finally, demethylation of the methoxy group of (VII) with BBr3 provided the required 8-hydroxyquinazolinone.
【1】 Griffin, R.J.; Srinivasan, S.; Bowman, K.; Calvert, A.H.; Curtin, N.J.; Newell, D.R.; Pemberton, L.C.; Golding, B.T.; Resistance-modifying agents. 5. Synthesis and biological properties of quinazolinone inhibitors of the DNA repair enzyme poly(ADP-ribose) polymerase (PARP). J Med Chem 1998, 41, 26, 5247. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
19273 | acetyl chloride | 75-36-5 | C2H3ClO | 详情 | 详情 | |
(II) | 25827 | 3-methoxy-2-nitrobenzoic acid | 4920-80-3 | C8H7NO5 | 详情 | 详情 |
(III) | 25828 | 3-methoxy-2-nitrobenzoyl chloride | C8H6ClNO4 | 详情 | 详情 | |
(IV) | 25829 | 3-methoxy-2-nitrobenzamide | C8H8N2O4 | 详情 | 详情 | |
(V) | 25830 | 2-amino-3-methoxybenzamide | C8H10N2O2 | 详情 | 详情 | |
(VI) | 25831 | 2-(acetamido)-3-methoxybenzamide | C10H12N2O3 | 详情 | 详情 | |
(VII) | 25832 | 8-methoxy-2-methyl-4(3H)-quinazolinone | C10H10N2O2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号:(II)Treatment of 3-methoxy-2-nitrobenzoic acid (I) with oxalyl chloride gave the corresponding acid chloride (II), which was then coupled with 2-amino-5-chloropyridine (III) to yield amide (IV). The reduction of the nitro group of (IV) using sodium hydrosulfite afforded aniline (V). Further chlorination of (V) with N-chlorosuccinimide furnished the 5-chloro derivative (VI).
【1】 Cheeseman, S.; Chou, Y.-L.; Ye, B.; et al.; Design, synthesis, and biological activity of novel non-amidine factor Xa inhibitors, 4: Optimization of hydrophilic substituents for potency and oral availability. 221st ACS Natl Meet (April 1 2001, San Diego) 2001, Abst MEDI 128. |
【2】 Snider, R.M.; Liang, A.M.; Wu, S.C.; Arnaiz, D.O.; Sacchi, K.L.; Kochanny, M.J.; Phillips, G.B.; Ye, B.; Zhao, Z.; Morrissey, M.M.; Griedel, B.D.; Lee, W.; Sakata, S.T.; Karanjawala, R.E.; Chou, Y.-L.; Shaw, K.J. (Schering AG); Ortho-anthranilamide derivs. as anticoagulants. EP 1040108; JP 2001526283; US 6140351; WO 9932477 . |
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) | 25827 | 3-methoxy-2-nitrobenzoic acid | 4920-80-3 | C8H7NO5 | 详情 | 详情 |
(II) | 25828 | 3-methoxy-2-nitrobenzoyl chloride | C8H6ClNO4 | 详情 | 详情 | |
(III) | 18559 | 5-Chloro-2-pyridinylamine; 5-Chloro-2-pyridinamine; 2-Amino-5-chloropyridine | 1072-98-6 | C5H5ClN2 | 详情 | 详情 |
(IV) | 51186 | N-(5-chloro-2-pyridinyl)-3-methoxy-2-nitrobenzamide | C13H10ClN3O4 | 详情 | 详情 | |
(V) | 51187 | 2-amino-N-(5-chloro-2-pyridinyl)-3-methoxybenzamide | C13H12ClN3O2 | 详情 | 详情 | |
(VI) | 51188 | C13H11Cl2N3O2 | 详情 | 详情 |