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【结 构 式】 
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【分子编号】28271 【品名】decanoyl chloride 【CA登记号】112-13-0 |
【 分 子 式 】C10H19ClO 【 分 子 量 】190.71296 【元素组成】C 62.98% H 10.04% Cl 18.59% O 8.39% |
合成路线1
该中间体在本合成路线中的序号：(VI)Protection of L-glutamic acid (I) with allyl alcohol and chlorotrimethylsilane produced the gamma-allyl ester (II). Subsequent treatment of (II) with fluorenylmethoxycarbonyl chloride afforded the N-Fmoc derivative (III). This was coupled to Wang resin using EDC and DMAP to provide the glutamate-coupled resin (IV). Removal of the Fmoc protecting group by means of piperidine gave (V), which was then condensed with decanoyl chloride (VI) yielding amide (VII). The allyl ester was then cleaved by treatment with Pd(PPh3)4 and the resulting carboxylic acid (VIII) was coupled with monoprotected diamine (IX) to furnish diamide (X). Deprotection of the allyl carbamate of (X) provided amine (XI).
| 【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 |
|---|---|---|---|---|---|---|
| (II), (V) | 28269 | (2S)-5-(allyloxy)-2-amino-5-oxopentanoic acid | C8H13NO4 | 详情 | 详情 | |
| (III), (IV) | 28270 | (2S)-5-(allyloxy)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-5-oxopentanoic acid | C23H23NO6 | 详情 | 详情 | |
| (I) | 12005 | L-2-Amino propane dicarboxylic acid; (-)-2-Aminoglutaric acid; L-2-Aminopentanoic acid; L-Glutamic acid | 56-86-0 | C5H9NO4 | 详情 | 详情 |
| (V) | 28269 | (2S)-5-(allyloxy)-2-amino-5-oxopentanoic acid | C8H13NO4 | 详情 | 详情 | |
| (VI) | 28271 | decanoyl chloride | 112-13-0 | C10H19ClO | 详情 | 详情 |
| (VII) | 28272 | (2S)-5-(allyloxy)-2-(decanoylamino)-5-oxopentanoic acid | C18H31NO5 | 详情 | 详情 | |
| (VIII) | 28273 | (2S)-2-(decanoylamino)pentanedioic acid | C15H27NO5 | 详情 | 详情 | |
| (IX) | 28274 | allyl 2-(benzylamino)ethylcarbamate | C13H18N2O2 | 详情 | 详情 | |
| (X) | 28275 | (2S)-5-[(2-[[(allyloxy)carbonyl]amino]ethyl)(benzyl)amino]-2-(decanoylamino)-5-oxopentanoic acid | C28H43N3O6 | 详情 | 详情 | |
| (XI) | 28276 | (2S)-5-[(2-aminoethyl)(benzyl)amino]-2-(decanoylamino)-5-oxopentanoic acid | C24H39N3O4 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)Coupling of decanoylchloride (I) with D-serine (II) under Schotten-Baumann conditions (with Na2CO3 in H2O/THF) provides N-decanoyl-D-serine (III). Separately, aldehyde (IV) is reduced by means of NaBH4 in EtOH to yield alcohol (V), whose nitro group is reduced by means of In and NH4Cl in EtOH to afford substituted aniline (VI). Coupling of 5-amino-2-hydroxybenzyl alcohol (VI) with serine (III) by means of dicyclohexylcarbodiimide (DCC) and 1-hydroxybenzotriazole (HOBt) in DMF furnishes compound (VII), which is finally oxidized with NaIO4 in MeOH/H2O to yield the desired spiroepoxide.
| 【1】 Giannis, A.; Arenz, C.; Synthesis of the first selective irreversible inhibitor of neutral sphingomyelinase. Angew Chem. Int Ed Engl 2000, 39, 8, 1440. |
| 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) | 28271 | decanoyl chloride | 112-13-0 | C10H19ClO | 详情 | 详情 |
| (II) | 15728 | (+)-2-Amino-3-hydroxypropionic acid; D-(+)-Serine; D-serine | 312-84-5 | C3H7NO3 | 详情 | 详情 |
| (III) | 47198 | (2R)-2-(decanoylamino)-3-hydroxypropionic acid | C13H25NO4 | 详情 | 详情 | |
| (IV) | 42307 | 2-hydroxy-5-nitrobenzaldehyde；5-nitrosalicylaldehyde | 97-51-8 | C7H5NO4 | 详情 | 详情 |
| (V) | 47199 | 2-(hydroxymethyl)-4-nitrophenol | C7H7NO4 | 详情 | 详情 | |
| (VI) | 47200 | 4-amino-2-(hydroxymethyl)phenol | C7H9NO2 | 详情 | 详情 | |
| (VII) | 47201 | N-[(1R)-2-[4-hydroxy-3-(hydroxymethyl)anilino]-1-(hydroxymethyl)-2-oxoethyl]decanamide | C20H32N2O5 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(VII)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4
该中间体在本合成路线中的序号：(VII)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 |