【结 构 式】 |
【分子编号】56891 【品名】1,3-propanediol cyclic sulfate;1,3,2-dioxathiane 2,2-dioxide;1,3-Propylene sulfate 【CA登记号】1073-05-8 |
【 分 子 式 】C3H6O4S 【 分 子 量 】138.14424 【元素组成】C 26.08% H 4.38% O 46.33% S 23.21% |
合成路线1
该中间体在本合成路线中的序号:(II)The reaction of (R)-(-)-5'-methoxylaudanosine (I) with 1,3-dioxa-2-thiane 2,2-dioxide (II) in hot acetone gives the quaternized propylsulfonate (III), which is treated with Ac-Cl in methanol to yield the intermediate isoquinolinium derivative (IV).
【1】 Samano, V.; et al.; Synthesis of ultra-short-acting neuromuscular blocker GW 0430: A remarkably stereo- and regioselective synthesis of mixed tetrahydroisquinolinium chlorofumarates. Org Lett 1999, 1, 12, 1993. |
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) | 19489 | (1R)-6,7-dimethoxy-2-methyl-1-(3,4,5-trimethoxybenzyl)-1,2,3,4-tetrahydroisoquinoline; 4-[[(1R)-6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydro-1-isoquinolinyl]methyl]-2,6-dimethoxyphenyl methyl ether | C22H29NO5 | 详情 | 详情 | |
(II) | 56891 | 1,3-propanediol cyclic sulfate;1,3,2-dioxathiane 2,2-dioxide;1,3-Propylene sulfate | 1073-05-8 | C3H6O4S | 详情 | 详情 |
(III) | 56892 | (1R,2S)-6,7-dimethoxy-2-methyl-2-[3-(sulfonatooxy)propyl]-1-(3,4,5-trimethoxybenzyl)-1,2,3,4-tetrahydroisoquinolinium | C25H35NO9S | 详情 | 详情 | |
(IV) | 56893 | (1R,2S)-2-(3-hydroxypropyl)-6,7-dimethoxy-2-methyl-1-(3,4,5-trimethoxybenzyl)-1,2,3,4-tetrahydroisoquinolinium chloride | C25H36ClNO6 | 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 reaction of (S)(+)-cryptostyline III (V) with 1,3-dioxa-2-thiane 2,2-dioxide (II) in hot acetonitrile gives the quaternized propylsulfonate (VI), which is treated with Ac-Cl in methanol to yield the intermediate isoquinolinium derivative (VII).
【1】 Samano, V.; et al.; Synthesis of ultra-short-acting neuromuscular blocker GW 0430: A remarkably stereo- and regioselective synthesis of mixed tetrahydroisquinolinium chlorofumarates. Org Lett 1999, 1, 12, 1993. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(II) | 56891 | 1,3-propanediol cyclic sulfate;1,3,2-dioxathiane 2,2-dioxide;1,3-Propylene sulfate | 1073-05-8 | C3H6O4S | 详情 | 详情 |
(V) | 56894 | 4-[(1S)-6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydro-1-isoquinolinyl]-2,6-dimethoxyphenyl methyl ether; (1S)-6,7-dimethoxy-2-methyl-1-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydroisoquinoline | C21H27NO5 | 详情 | 详情 | |
(VI) | 56895 | (1S,2R)-6,7-dimethoxy-2-methyl-2-[3-(sulfonatooxy)propyl]-1-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydroisoquinolinium | C24H33NO9S | 详情 | 详情 | |
(VII) | 56896 | (1S,2R)-2-(3-hydroxypropyl)-6,7-dimethoxy-2-methyl-1-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydroisoquinolinium chloride | C24H34ClNO6 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号:(XXVIII)Alkylation of 4’-hydroxy-3’-methoxyacetophenone (XVII) with benzyl bromide by means of K2CO3 in DMF gives benzyl ether (XVIII), which is reacted with fuming HNO3 and concentrated H2SO4 in cold CH2Cl2 to afford 4’-benzyloxy-5’-methoxy-2’-nitroacetophenone (XIX). After reduction of the nitro group of compound (XIX) using iron powder and ammonium formate in refluxing H2O/toluene, the resulting 2-aminoacetophenone derivative (XX) cyclizes with ethyl formate (XXI) in the presence of NaOEt in DME, providing 7-benzyloxy-6-methoxy-4-quinolinol (XXII). Finally, quinolinol (XXII) is treated with trifluoromethanesulfonyl chloride in the presence of DMAP and 2,6-lutidine in cold CH2Cl2 .
【1】 Deschamps, N.M., Martin, M.T., Monteith, M.J., Zhou, X. (GlaxoSmithKline Inc.). Preparation of a quinolinyloxydiphenylcyclopropanedicarboxamide. US 2010081805, WO 010036831. |
【2】 Wilson, J., Zuberi, S., Naganathan, S., Goldman, E., Kanter, J. (Exelixis, Inc.). Methods of preparing quinoline derivatives. WO 2010056960. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(XXIVa) | 22605 | 4-(3-Chloropropoxy)-3-Methoxyacetophenone;3-(4-Acetyl-2-methoxyphenoxy)propyl chloride;1-(4-(3-chloropropoxy)-3-methoxyphenyl)ethanone;1-[4-(3-chloropropoxy)-3-methoxyphenyl]-1-ethanone | 58113-30-7 | C12H15ClO3 | 详情 | 详情 |
(XXIVb) | 69115 | 1-(4-(3-bromopropoxy)-3-methoxyphenyl)ethanone | C12H15BrO3 | 详情 | 详情 | |
(XXVa) | 69117 | 1-(4-(3-chloropropoxy)-5-methoxy-2-nitrophenyl)ethanone | C12H14ClNO5 | 详情 | 详情 | |
(XXVb) | 69116 | 1-(4-(3-bromopropoxy)-5-methoxy-2-nitrophenyl)ethanone | C12H14BrNO5 | 详情 | 详情 | |
(VI) | 69105 | 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinoline;4-(3-((4-chloro-6-methoxyquinolin-7-yl)oxy)propyl)morpholine | C17H21ClN2O3 | 详情 | 详情 | |
(XVII) | 22604 | 1-(4-hydroxy-3-methoxyphenyl)-1-ethanone;Acetovanillone;4’-hydroxy-3’-methoxyacetophenone;1-(4-hydroxy-3-methoxyphenyl)ethanone | 498-02-2 | C9H10O3 | 详情 | 详情 |
(XXI) | 16602 | ethyl formate | 109-94-4 | C3H6O2 | 详情 | 详情 |
(XXIII) | 10358 | 1-Bromo-3-chloropropane | 109-70-6 | C3H6BrCl | 详情 | 详情 |
(XXVI) | 10388 | Morpholine | 110-91-8 | C4H9NO | 详情 | 详情 |
(XXVII) | 69118 | 1-(5-methoxy-4-(3-morpholinopropoxy)-2-nitrophenyl)ethanone | C16H22N2O6 | 详情 | 详情 | |
(XXVIII) | 56891 | 1,3-propanediol cyclic sulfate;1,3,2-dioxathiane 2,2-dioxide;1,3-Propylene sulfate | 1073-05-8 | C3H6O4S | 详情 | 详情 |
(XXIX) | 69119 | 4’-(morpholinopropoxy)acetophenone;1-(3-methoxy-4-(3-morpholinopropoxy)phenyl)ethanone | C16H23NO4 | 详情 | 详情 | |
(XXX) | 69120 | 1-(2-amino-5-methoxy-4-(3-morpholinopropoxy)phenyl)ethanone | C16H24N2O4 | 详情 | 详情 | |
(XXXI) | 69121 | 6-methoxy-7-(3-morpholinopropoxy)quinolin-4-ol | C17H22N2O4 | 详情 | 详情 | |
(XXXII) | 20360 | methyl(phenyl)formamide;N-Methylformanilide;N-Formyl-N-methylaniline;Methylphenylformamide;N-methyl-N-phenylformamide;N-Methyl-N-formylaniline;N-Formyl-N-methylaniline | 93-61-8 | C8H9NO | 详情 | 详情 |