• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】51680

【品名】methyl 2-ethoxy-3-[4-[2-(10H-phenoxazin-10-yl)ethoxy]phenyl]propanoate

【CA登记号】

【 分 子 式 】C26H27NO5

【 分 子 量 】433.50412

【元素组成】C 72.04% H 6.28% N 3.23% O 18.45%

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:(IX)

Several related procedures have been described for the synthesis of the title compound. The Horner-Emmons reaction of 4-benzyloxybenzaldehyde (I) with triethyl 2-ethoxyphosphonoacetate (II) afforded the unsaturated ester (IIIa-b) as a mixture of E/Z isomers. Simultaneous double-bond hydrogenation and benzyl group hydrogenolysis in the presence of Pd/C furnished phenol (IV). Alternatively, double-bond reduction by means of magnesium in MeOH was accompanied by transesterification, yielding the saturated methyl ester (V). Further benzyl group hydrogenolysis of (V) over Pd/C gave phenol (VI). The alkylation of phenols (IV) and (VI) with the phenoxazinylethyl mesylate (VII) provided the corresponding ethers (VIII) and (IX), respectively. The racemic carboxylic acid (X) was then obtained by hydrolysis of either ethyl- (VIII) or methyl- (IX) esters under basic conditions.

1 Kalchar, S.; Lohray, V.B.; Lohray, B.B.; Chakrabarti, R.; Bajji, A.C.; Ramanujam, R. (Dr. Reddy's Research Foundation); Novel tricyclic cpds. and their use in medicine; process for their preparation and pharmaceutical compsns. containing them. EP 1049684; JP 2001519422; WO 9919313 .
2 Rajagopalan, R.; Ashok, C.B.; Shivaramayya, K.; Gurram, R.M.; Lohray, B.B.; Paraselli, B.R.; Rajan, C.; Lohray, V.B. (Dr. Reddy's Research Foundation); Novel tricyclic cpds. and their use in medicine; process for their preparation and pharmaceutical compsn. containing them. EP 1155006; WO 0050414 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(IIIa) 50411 ethyl (E)-3-[4-(benzyloxy)phenyl]-2-ethoxy-2-propenoate C20H22O4 详情 详情
(IIIb) 51683 ethyl (Z)-3-[4-(benzyloxy)phenyl]-2-ethoxy-2-propenoate C20H22O4 详情 详情
(I) 29179 4-(Benzyloxy)benzaldehyde 4397-53-9 C14H12O2 详情 详情
(II) 51675 ethyl 2-(diethoxyphosphoryl)-2-ethoxyacetate C10H21O6P 详情 详情
(IV) 51682 ethyl 2-ethoxy-3-(4-hydroxyphenyl)propanoate C13H18O4 详情 详情
(V) 51676 methyl 3-[4-(benzyloxy)phenyl]-2-ethoxypropanoate C19H22O4 详情 详情
(VI) 51677 methyl 2-ethoxy-3-(4-hydroxyphenyl)propanoate C12H16O4 详情 详情
(VII) 51678 2-(10H-phenoxazin-10-yl)ethyl methanesulfonate C15H15NO4S 详情 详情
(VIII) 51679 ethyl 2-ethoxy-3-[4-[2-(10H-phenoxazin-10-yl)ethoxy]phenyl]propanoate C27H29NO5 详情 详情
(IX) 51680 methyl 2-ethoxy-3-[4-[2-(10H-phenoxazin-10-yl)ethoxy]phenyl]propanoate C26H27NO5 详情 详情
(X) 51681 2-ethoxy-3-[4-[2-(10H-phenoxazin-10-yl)ethoxy]phenyl]propionic acid C25H25NO5 详情 详情

合成路线2

该中间体在本合成路线中的序号:(IX)

In a related method, 4-(2-bromoethoxy)benzaldehyde (XI) was subjected to a Horner-Emmons reaction with phosphonate (II) to produce the unsaturated ester (XIIa-b), which was further hydrogenated to afford (XIII). Alkylation of phenoxazine (XIV) with bromide (XIII) gave adduct (VIII) (1,2). In a different reaction sequence, bromoaldehyde (XI) was initially condensed with phenoxazine (XIV), producing adduct (XV). This was subjected to Horner-Emmons condensation with (II) to give the unsaturated ester (XVIa-b), which was then hydrogenated to (VIII). Alternatively, double-bond reduction of (XVI) by means of Mg in MeOH gave rise to the transesterified methyl ester (IX). Ester hydrolysis as above provided acid (X).

2 Kalchar, S.; Lohray, V.B.; Lohray, B.B.; Chakrabarti, R.; Bajji, A.C.; Ramanujam, R. (Dr. Reddy's Research Foundation); Novel tricyclic cpds. and their use in medicine; process for their preparation and pharmaceutical compsns. containing them. EP 1049684; JP 2001519422; WO 9919313 .
3 Rajagopalan, R.; Ashok, C.B.; Shivaramayya, K.; Gurram, R.M.; Lohray, B.B.; Paraselli, B.R.; Rajan, C.; Lohray, V.B. (Dr. Reddy's Research Foundation); Novel tricyclic cpds. and their use in medicine; process for their preparation and pharmaceutical compsn. containing them. EP 1155006; WO 0050414 .
1 Lohray, B.B.; et al.; (-)-3-[4-[2-(Phenoxazin-10-yl)ethoxy]phenyl]-2-ethoxypropanoic acid[(-)DRF 2725]: A dual PPAR agonist with potent antihyperglycemic and lipid modulating activity. J Med Chem 2001, 44, 16, 2675.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XIIa) 51686 ethyl (E)-3-[4-(2-bromoethoxy)phenyl]-2-ethoxy-2-propenoate C15H19BrO4 详情 详情
(XIIb) 51687 ethyl (Z)-3-[4-(2-bromoethoxy)phenyl]-2-ethoxy-2-propenoate C15H19BrO4 详情 详情
(XVIa) 51689 ethyl (E)-2-ethoxy-3-[4-[2-(10H-phenoxazin-10-yl)ethoxy]phenyl]-2-propenoate C27H27NO5 详情 详情
(XVba) 51690 ethyl (Z)-2-ethoxy-3-[4-[2-(10H-phenoxazin-10-yl)ethoxy]phenyl]-2-propenoate C27H27NO5 详情 详情
(II) 51675 ethyl 2-(diethoxyphosphoryl)-2-ethoxyacetate C10H21O6P 详情 详情
(VIII) 51679 ethyl 2-ethoxy-3-[4-[2-(10H-phenoxazin-10-yl)ethoxy]phenyl]propanoate C27H29NO5 详情 详情
(IX) 51680 methyl 2-ethoxy-3-[4-[2-(10H-phenoxazin-10-yl)ethoxy]phenyl]propanoate C26H27NO5 详情 详情
(X) 51681 2-ethoxy-3-[4-[2-(10H-phenoxazin-10-yl)ethoxy]phenyl]propionic acid C25H25NO5 详情 详情
(XI) 18799 4-(2-bromoethoxy)benzaldehyde 52191-15-8 C9H9BrO2 详情 详情
(XIII) 51688 ethyl 3-[4-(2-bromoethoxy)phenyl]-2-ethoxypropanoate C15H21BrO4 详情 详情
(XIV) 51684 2,3,5,6-Dibenzo-1,4-oxazine; Phenoxazine 135-67-1 C12H9NO 详情 详情
(XV) 51685 4-[2-(10H-phenoxazin-10-yl)ethoxy]benzaldehyde C21H17NO3 详情 详情
Extended Information