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【结 构 式】

【分子编号】25196

【品名】[1-(2-methoxyphenyl)-4-piperidinyl]methylamine; [1-(2-methoxyphenyl)-4-piperidinyl]methanamine

【CA登记号】

【 分 子 式 】C13H20N2O

【 分 子 量 】220.31468

【元素组成】C 70.87% H 9.15% N 12.72% O 7.26%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(VII)

Condensation of isonicotinamide (I) with 1-chloro-2,4-dinitrobenzene (II) gave quaternary pyridinium salt (III). This was further converted into pyridinium salt (V) by treatment with 2-methoxyaniline (IV) in MeOH. Catalytic transfer hydrogenation of the pyridine ring of (V) provided piperidine (VI). The amide function of (VI) was then reduced to amine (VII) using either borane-dimethyl sulfide complex or LiAlH4. Condensation of 4-chlorocatechol (VIII) with epichlorohydrin (IX) in aqueous KOH produced a mixture of regioisomeric benzodioxans (X) and (XI), from which the major 7-chloro isomer (X) was isolated by flash chromatography after treatment with tosyl chloride and pyridine yielding tosylate (XII). This compound was finally coupled with amine (VII) in the presence of K2CO3 and KI in boiling acetonitrile.

1 Kerrigan, F.; Heal, D.J.; Martin, K.F. (The Boots Company plc); Bicyclic aromatic cpds. as therapeutic agents. EP 0717739; JP 1997502431; US 5767116; WO 9507274 .
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) 25191 isonicotinamide 1453-82-3 C6H6N2O 详情 详情
(II) 10378 1-Chloro-2,4-dinitrobenzene 97-00-7 C6H3ClN2O4 详情 详情
(III) 25192 4-(aminocarbonyl)-1-(2,4-dinitrophenyl)pyridinium chloride 475-25-2 C12H9ClN4O5 详情 详情
(IV) 25193 2-methoxyphenylamine; 2-methoxyaniline 517-28-2 C7H9NO 详情 详情
(V) 25194 4-(aminocarbonyl)-1-(2-methoxyphenyl)pyridinium chloride C13H13ClN2O2 详情 详情
(VI) 25195 1-(2-methoxyphenyl)-4-piperidinecarboxamide C13H18N2O2 详情 详情
(VII) 25196 [1-(2-methoxyphenyl)-4-piperidinyl]methylamine; [1-(2-methoxyphenyl)-4-piperidinyl]methanamine C13H20N2O 详情 详情
(VIII) 25197 4-chloro-1,2-benzenediol 2138-22-9 C6H5ClO2 详情 详情
(IX) 10146 Epichlorohydrin; 2-(Chloromethyl)oxirane 106-89-8 C3H5ClO 详情 详情
(X) 25199 (7-chloro-2,3-dihydro-1,4-benzodioxin-2-yl)methanol C9H9ClO3 详情 详情
(XI) 25198 (6-chloro-2,3-dihydro-1,4-benzodioxin-2-yl)methanol C9H9ClO3 详情 详情
(XII) 25200 (7-chloro-2,3-dihydro-1,4-benzodioxin-2-yl)methyl 4-methylbenzenesulfonate C16H15ClO5S 详情 详情

合成路线2

该中间体在本合成路线中的序号:(VII)

The reaction of 5-chloro-2-hydroxybenzaldehyde (I) with the chiral glycidyl tosylate (II) by means of K2CO3 in DMF gives the condensation product (III), which is oxidized with m-chloroperbenzoic acid to formyl ester (IV). The cyclization of (IV) with sodium methoxide in methanol affords the hydroxymethyl benzodioxane (V), which is tosylated with tosyl chloride in pyridine to the tosylate (VI). Finally, this compound is condensed with 1-(2-methoxyphenyl)piperidin-4-ylmethylamine (VII) by means of K2CO3 in refluxing acetonitrile.

1 Birch, A.M.; Needham, P.L.; Kerrigan, F.; Gill, J.C.; Bradley, P.A.; N-substituted (2,3-dihydro-1,4-benzodioxin-2-yl)methylamine derivatives as D2 antagonists/5HT1A partial agonists with potential as atypical antipsychotic agents. J Med Chem 1999, 42, 17, 3342.
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) 26408 5-chlorosalicylaldehyde; 5-chloro-2-hydroxybenzaldehyde 635-93-8 C7H5ClO2 详情 详情
(II) 16242 (2R)oxiranylmethyl 4-methylbenzenesulfonate; (2R)-(-)-Glycidyl tosylate 113826-06-5 C10H12O4S 详情 详情
(III) 26409 5-chloro-2-[(2R)oxiranylmethoxy]benzaldehyde C10H9ClO3 详情 详情
(IV) 26410 5-chloro-2-[(2R)oxiranylmethoxy]phenyl formate C10H9ClO4 详情 详情
(V) 26411 [(2S)-7-chloro-2,3-dihydro-1,4-benzodioxin-2-yl]methanol C9H9ClO3 详情 详情
(VI) 26412 [(2R)-7-chloro-2,3-dihydro-1,4-benzodioxin-2-yl]methyl 4-methylbenzenesulfonate C16H15ClO5S 详情 详情
(VII) 25196 [1-(2-methoxyphenyl)-4-piperidinyl]methylamine; [1-(2-methoxyphenyl)-4-piperidinyl]methanamine C13H20N2O 详情 详情
Extended Information