【结 构 式】 |
【分子编号】56506 【品名】4-chloro-3-methoxy-2-methyl-1-pyridiniumolate 【CA登记号】 |
【 分 子 式 】C7H8ClNO2 【 分 子 量 】173.59876 【元素组成】C 48.43% H 4.64% Cl 20.42% N 8.07% O 18.43% |
合成路线1
该中间体在本合成路线中的序号:(XX)In an alternative procedure, the nitropyridine N-oxide (IX) was rearranged to the (mesyloxymethyl)pyridine (XIX) by treatment with methanesulfonic anhydride. Condensation of mesylate (XIX) with mercaptobenzimidazole (V), with concomitant nitro group displacement in the presence of sodium methoxide led to the sulfide precursor (XIV). This was then oxidized to the title sulfoxide employing sodium percarbonate and ammonium molybdate. An analogous synthetic route starting from the chloropyridine N-oxide (XX) provided mesylate (XXI), which was condensed with (V) in the presence of Et3N, leading to the sulfide adduct (XXII). The 4-chloro group of (XXII) was then displaced by sodium methoxide producing the dimethoxypyridine derivative (XIV).
【1】 Coppi, L.; Berenguer Maimó, R. (Laboratorios del Dr. Esteve, SA); Method for obtaining derivs. of [[pyridyl substd.)methyl]thio]benzimidazol. ES 2171116; WO 0179194 . |
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) | 14034 | 5-(Difluoromethoxy)-1H-benzimidazole-2-thiol; 5-(Difluoromethoxy)-1H-benzimidazol-2-ylhydrosulfide; 5-Difluoromethoxy-2-mercapto-1H-benzimidazole | 97963-62-7 | C8H6F2N2OS | 详情 | 详情 |
(IX) | 56498 | 3-methoxy-2-methyl-4-nitro-1-pyridiniumolate | C7H8N2O4 | 详情 | 详情 | |
(XIV) | 14036 | 5-(Difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)methyl]sulfanyl]-1H-benzimidazole; 2-([[5-(Difluoromethoxy)-1H-benzimidazol-2-yl]sulfanyl]methyl)-3-methoxy-4-pyridinyl methyl ether | 102625-64-9 | C16H15F2N3O3S | 详情 | 详情 |
(XIX) | 56505 | (3-methoxy-4-nitro-2-pyridinyl)methyl methanesulfonate | C8H10N2O6S | 详情 | 详情 | |
(XX) | 56506 | 4-chloro-3-methoxy-2-methyl-1-pyridiniumolate | C7H8ClNO2 | 详情 | 详情 | |
(XXI) | 56507 | (4-chloro-3-methoxy-2-pyridinyl)methyl methanesulfonate | C8H10ClNO4S | 详情 | 详情 | |
(XXII) | 56508 | 4-chloro-2-({[5-(difluoromethoxy)-1H-benzimidazol-2-yl]sulfanyl}methyl)-3-pyridinyl methyl ether; 2-{[(4-chloro-3-methoxy-2-pyridinyl)methyl]sulfanyl}-5-(difluoromethoxy)-1H-benzimidazole | C15H12ClF2N3O2S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号:(XX)Similarly, rearrangement of the chloropyridine N-oxide (XX) using acetic anhydride produced acetate ester (XXIII), which was further hydrolyzed to the pyridine alcohol (XXIV). The chloromethyl pyridine (XXV), obtained by treatment of alcohol (XXIV) with SOCl2, was condensed with the mercaptobenzimidazole (V) in the presence of tetramethylguanidine producing sulfide (XXII). Conversion of (XXII) to the title compound was then performed by oxidation to sulfoxide (XXVI) employing sodium percarbonate, followed by chloride displacement with potassium methoxide.
【1】 Palomo Coll, A.; A process for the preparation of pantoprazole and intermediates therefor. WO 0228852 . |
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) | 14034 | 5-(Difluoromethoxy)-1H-benzimidazole-2-thiol; 5-(Difluoromethoxy)-1H-benzimidazol-2-ylhydrosulfide; 5-Difluoromethoxy-2-mercapto-1H-benzimidazole | 97963-62-7 | C8H6F2N2OS | 详情 | 详情 |
(XX) | 56506 | 4-chloro-3-methoxy-2-methyl-1-pyridiniumolate | C7H8ClNO2 | 详情 | 详情 | |
(XXII) | 56508 | 4-chloro-2-({[5-(difluoromethoxy)-1H-benzimidazol-2-yl]sulfanyl}methyl)-3-pyridinyl methyl ether; 2-{[(4-chloro-3-methoxy-2-pyridinyl)methyl]sulfanyl}-5-(difluoromethoxy)-1H-benzimidazole | C15H12ClF2N3O2S | 详情 | 详情 | |
(XXIII) | 56509 | (4-chloro-3-methoxy-2-pyridinyl)methyl acetate | C9H10ClNO3 | 详情 | 详情 | |
(XXIV) | 56510 | (4-chloro-3-methoxy-2-pyridinyl)methanol | C7H8ClNO2 | 详情 | 详情 | |
(XXV) | 56511 | 4-chloro-2-(chloromethyl)-3-methoxypyridine; 4-chloro-2-(chloromethyl)-3-pyridinyl methyl ether | C7H7Cl2NO | 详情 | 详情 | |
(XXVI) | 56512 | (4-chloro-3-methoxy-2-pyridinyl)methyl 5-(difluoromethoxy)-1H-benzimidazol-2-yl sulfoxide; 2-{[(4-chloro-3-methoxy-2-pyridinyl)methyl]sulfinyl}-5-(difluoromethoxy)-1H-benzimidazole | C15H12ClF2N3O3S | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号:(I)
【1】 Palomo Coll A. 2002. A process for the preparation of pantoprazole and intermediates thereof. WO 2002028852(本专利属于Dmamite Dipharma, Italy) |
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) | 56506 | 4-chloro-3-methoxy-2-methyl-1-pyridiniumolate | C7H8ClNO2 | 详情 | 详情 | |
(II) | 56510 | (4-chloro-3-methoxy-2-pyridinyl)methanol | C7H8ClNO2 | 详情 | 详情 | |
(III) | 56511 | 4-chloro-2-(chloromethyl)-3-methoxypyridine; 4-chloro-2-(chloromethyl)-3-pyridinyl methyl ether | C7H7Cl2NO | 详情 | 详情 | |
(IV) | 66569 | 5-(difluoromethoxy)-1H-benzo[d]imidazole-2(3H)-thione | 97963-62-7 | C8H6F2N2OS | 详情 | 详情 |
(V) | 56508 | 4-chloro-2-({[5-(difluoromethoxy)-1H-benzimidazol-2-yl]sulfanyl}methyl)-3-pyridinyl methyl ether; 2-{[(4-chloro-3-methoxy-2-pyridinyl)methyl]sulfanyl}-5-(difluoromethoxy)-1H-benzimidazole | C15H12ClF2N3O2S | 详情 | 详情 | |
(VI) | 56508 | 4-chloro-2-({[5-(difluoromethoxy)-1H-benzimidazol-2-yl]sulfanyl}methyl)-3-pyridinyl methyl ether; 2-{[(4-chloro-3-methoxy-2-pyridinyl)methyl]sulfanyl}-5-(difluoromethoxy)-1H-benzimidazole | C15H12ClF2N3O2S | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号:(I)
【1】 Coppi L,Berenguer Maimo R. 2001. Method for obtaining derivatives of[[(substituted-pyridyl) methyl] thio] benzimidazole, useful as intermediates for omeprazole and related antiulcer agents. W0 2001079194 (本专利属于Esteve Quimica,S A, Spain) |
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) | 56506 | 4-chloro-3-methoxy-2-methyl-1-pyridiniumolate | C7H8ClNO2 | 详情 | 详情 | |
(II) | 56507 | (4-chloro-3-methoxy-2-pyridinyl)methyl methanesulfonate | C8H10ClNO4S | 详情 | 详情 | |
(III) | 66569 | 5-(difluoromethoxy)-1H-benzo[d]imidazole-2(3H)-thione | 97963-62-7 | C8H6F2N2OS | 详情 | 详情 |
(IV) | 56508 | 4-chloro-2-({[5-(difluoromethoxy)-1H-benzimidazol-2-yl]sulfanyl}methyl)-3-pyridinyl methyl ether; 2-{[(4-chloro-3-methoxy-2-pyridinyl)methyl]sulfanyl}-5-(difluoromethoxy)-1H-benzimidazole | C15H12ClF2N3O2S | 详情 | 详情 |