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【结 构 式】 
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【分子编号】28277 【品名】2,5-diphenyl-1,3-oxazole-4-carboxylic acid 【CA登记号】 |
【 分 子 式 】C16H11NO3 【 分 子 量 】265.26828 【元素组成】C 72.45% H 4.18% N 5.28% O 18.09% |
合成路线1
该中间体在本合成路线中的序号：(XII)Amine (XI) was coupled to isoxazolecarboxylic acid (XII) to give (XIII). which was finally liberated from the resin by cleavage with trifluoroacetic acid in CH2Cl2.
| 【1】 Wipf, P.; et al.; Combinatorial synthesis and biological evaluation of library of small-molecule Ser/Thr-protein phosphatase inhibitors. Bioorg Med Chem 1997, 5, 1, 165. |
| 【2】 Lazo, J.S.; Rice, R.L.; Cunningham, A.; Wipf, P. (University of Pittsburgh); Phosphatase inhibitors and methods of use thereof. EP 0959884; US 5700821; WO 9804257 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XI) | 28276 | (2S)-5-[(2-aminoethyl)(benzyl)amino]-2-(decanoylamino)-5-oxopentanoic acid | C24H39N3O4 | 详情 | 详情 | |
| (XII) | 28277 | 2,5-diphenyl-1,3-oxazole-4-carboxylic acid | C16H11NO3 | 详情 | 详情 | |
| (XIII) | 28278 | (2S)-5-[benzyl(2-[[(2,5-diphenyl-1,3-oxazol-4-yl)carbonyl]amino]ethyl)amino]-2-(decanoylamino)-5-oxopentanoic acid | C40H48N4O6 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XIII)D,L-Glutamic acid (I) was sequentially protected as the gamma-allyl ester (III), upon treatment with allyl alcohol (II) and chlorotrimethylsilane, followed by conversion to the trichloroethyl carbamate (V) by means of chloroformate (IV), and then reaction of (V) with benzyl bromide to afford the alpha-benzyl ester (VI). Deprotection of the trichloroethyl carbamate of (VI) by treatment with zinc dust and HOAc and subsequent condensation of the resulting amine with decanoyl chloride (VII) furnished amide (VIII). The allyl ester of (VIII) was then selectively cleaved by using tetrakistriphenylphosphine palladium(0) and morpholine to give carboxylic acid (IX). trans-1,2-Diaminocyclohexane (X) was protected as the mono tert-butyl carbamate (XI) and then coupled with acid (IX) in the presence of diethylphosphoryl cyanide to yield amide (XII). After acidic Boc cleavage of (XII), coupling of the resulting amine with 2,5-diphenyloxazole-4-carboxylic acid (XIII) by means of bromo-tris(pyrrolidino)phosphonium hexafluorophosphate (PyBroP) afforded (XIV). Finally, hydrolysis of the benzyl ester of (XIV) with LiOH provided the corresponding carboxylic acid.
| 【1】 Ducruet, A.P.; Yokokawa, F.; Rice, R.L.; tamura, K.; Lazo, J.S.; Wipf, P.; Yokokama, S.; Identification of new Cdc25 dual specificity phosphatase inhibitors in a targeted small molecule array. Bioorg Med Chem 2000, 8, 6, 1451. |
| 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) | 28752 | DL-2-Amino propane dicarboxylic acid; DL-2-Aminopentanoic acid; glutamic acid; DL-glutamic acid; (+/-)-2-Aminoglutaric acid | 617-65-2 | C5H9NO4 | 详情 | 详情 |
| (II) | 12234 | 2-Propen-1-ol; Allyl alcohol | 107-18-6 | C3H6O | 详情 | 详情 |
| (III) | 43406 | 5-(allyloxy)-5-oxonorvaline | C8H13NO4 | 详情 | 详情 | |
| (IV) | 13664 | 1,1,1-Trichloro-2-[(chlorocarbonyl)oxy]ethane; 2,2,2-Trichloroethyl chloroformate | 17341-93-4 | C3H2Cl4O2 | 详情 | 详情 |
| (V) | 43399 | 5-(allyloxy)-5-oxo-N-[(2,2,2-trichloroethoxy)carbonyl]norvaline | C11H14Cl3NO6 | 详情 | 详情 | |
| (VI) | 43400 | 5-allyl 1-benzyl 2-[[(2,2,2-trichloroethoxy)carbonyl]amino]pentanedioate | C18H20Cl3NO6 | 详情 | 详情 | |
| (VII) | 28271 | decanoyl chloride | 112-13-0 | C10H19ClO | 详情 | 详情 |
| (VIII) | 43401 | 5-allyl 1-benzyl 2-(decanoylamino)pentanedioate | C25H37NO5 | 详情 | 详情 | |
| (IX) | 43402 | 5-(benzyloxy)-4-(decanoylamino)-5-oxopentanoic acid | C22H33NO5 | 详情 | 详情 | |
| (X) | 11300 | 2-hydroxyethyl 4-hydroxy-1,1-dioxo-1,2-dihydro-1lambda(6),2-benzothiazine-3-carboxylate | C11H11NO6S | 详情 | 详情 | |
| (XI) | 43403 | tert-butyl (1R,2R)-2-aminocyclohexylcarbamate | C11H22N2O2 | 详情 | 详情 | |
| (XII) | 43404 | benzyl 5-([(1R,2R)-2-[(tert-butoxycarbonyl)amino]cyclohexyl]amino)-2-(decanoylamino)-5-oxopentanoate | C33H53N3O6 | 详情 | 详情 | |
| (XIII) | 28277 | 2,5-diphenyl-1,3-oxazole-4-carboxylic acid | C16H11NO3 | 详情 | 详情 | |
| (XIV) | 43405 | benzyl 2-(decanoylamino)-5-[((1R,2R)-2-[[(2,5-diphenyl-1,3-oxazol-4-yl)carbonyl]amino]cyclohexyl)amino]-5-oxopentanoate | C44H54N4O6 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(XIII)D,L-Glutamic acid (I) was sequentially protected as the gamma-allyl ester (III), upon treatment with allyl alcohol (II) and chlorotrimethylsilane, followed by conversion to the trichloroethyl carbamate (V) by means of chloroformate (IV), and then reaction of (V) with benzyl bromide to afford the alpha-benzyl ester (VI). Deprotection of the trichloroethyl carbamate of (VI) by treatment with zinc dust and HOAc and subsequent condensation of the resulting amine with decanoyl chloride (VII) furnished amide (VIII). The allyl ester of (VIII) was then selectively cleaved by using tetrakistriphenylphosphine palladium(0) and morpholine to give carboxylic acid (IX). trans-1,4-Diaminocyclohexane (X) was protected as the mono tert-butyl carbamate (XI) and then coupled with acid (IX) in the presence of diethylphosphoryl cyanide to yield amide (XII). After acidic Boc cleavage of (XII), coupling of the resulting amine with 2,5-diphenyloxazole-4-carboxylic acid (XIII) by means of bromo-tris(pyrrolidino)phosphonium hexafluorophosphate (PyBroP) afforded (XIV). Finally, hydrolysis of the benzyl ester of (XIV) with LiOH provided the corresponding carboxylic acid.
| 【1】 Ducruet, A.P.; Yokokawa, F.; Rice, R.L.; tamura, K.; Lazo, J.S.; Wipf, P.; Yokokama, S.; Identification of new Cdc25 dual specificity phosphatase inhibitors in a targeted small molecule array. Bioorg Med Chem 2000, 8, 6, 1451. |
| 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) | 28752 | DL-2-Amino propane dicarboxylic acid; DL-2-Aminopentanoic acid; glutamic acid; DL-glutamic acid; (+/-)-2-Aminoglutaric acid | 617-65-2 | C5H9NO4 | 详情 | 详情 |
| (II) | 12234 | 2-Propen-1-ol; Allyl alcohol | 107-18-6 | C3H6O | 详情 | 详情 |
| (III) | 43406 | 5-(allyloxy)-5-oxonorvaline | C8H13NO4 | 详情 | 详情 | |
| (IV) | 13664 | 1,1,1-Trichloro-2-[(chlorocarbonyl)oxy]ethane; 2,2,2-Trichloroethyl chloroformate | 17341-93-4 | C3H2Cl4O2 | 详情 | 详情 |
| (V) | 43399 | 5-(allyloxy)-5-oxo-N-[(2,2,2-trichloroethoxy)carbonyl]norvaline | C11H14Cl3NO6 | 详情 | 详情 | |
| (VI) | 43400 | 5-allyl 1-benzyl 2-[[(2,2,2-trichloroethoxy)carbonyl]amino]pentanedioate | C18H20Cl3NO6 | 详情 | 详情 | |
| (VII) | 28271 | decanoyl chloride | 112-13-0 | C10H19ClO | 详情 | 详情 |
| (VIII) | 43401 | 5-allyl 1-benzyl 2-(decanoylamino)pentanedioate | C25H37NO5 | 详情 | 详情 | |
| (IX) | 43402 | 5-(benzyloxy)-4-(decanoylamino)-5-oxopentanoic acid | C22H33NO5 | 详情 | 详情 | |
| (X) | 43407 | 4-aminocyclohexylamine; 1,4-cyclohexanediamine | 3114-70-3 | C6H14N2 | 详情 | 详情 |
| (XI) | 43408 | tert-butyl 4-aminocyclohexylcarbamate | C11H22N2O2 | 详情 | 详情 | |
| (XII) | 43409 | benzyl 5-([4-[(tert-butoxycarbonyl)amino]cyclohexyl]amino)-2-(decanoylamino)-5-oxopentanoate | C33H53N3O6 | 详情 | 详情 | |
| (XIII) | 28277 | 2,5-diphenyl-1,3-oxazole-4-carboxylic acid | C16H11NO3 | 详情 | 详情 | |
| (XIV) | 43410 | benzyl 2-(decanoylamino)-5-[(4-[[(2,5-diphenyl-1,3-oxazol-4-yl)carbonyl]amino]cyclohexyl)amino]-5-oxopentanoate | C44H54N4O6 | 详情 | 详情 |