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【结 构 式】 
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【分子编号】11591 【品名】methyl (2R)-2-hydroxypropanoate 【CA登记号】17392-83-5 |
【 分 子 式 】C4H8O3 【 分 子 量 】104.10572 【元素组成】C 46.15% H 7.75% O 46.11% |
合成路线1
该中间体在本合成路线中的序号：(XXIV)The starting compounds (I) and (II) are obtained as follows: Aldehyde (I): The esterification of (R,R)-dihydrobenzoin (IX) with acryloyl chloride (X) by means of triethylamine in dichloromethane gives the corresponding diester (XI), which by bis-cyclization with butadiene (XII) by means of TiCl4 in dichloromethane yields the bis(3-cyclohexenecarboxylic acid) ester (XIII). The hydrolysis of (XIII) with LiOH in methanol affords (R)-3-cyclohexenecarboxylic acid (XIV), which by reaction with I2, KI and NaHCO3 is converted to the iodolactone (XV). The reaction of (XV) with 1,5-diazabicyclo[5.4.0]-5-undecene (DBU) in refluxing THF affords the unsaturated lactone (XVI), which by treatment with NaHCO3 in anhydrous methanol yields (1R,3R)-3-hydroxy-4-cyclohexenecarboxylic acid methyl ester (XVII). The methylation of (XVII) with methyl trifluoromethanesulfonate and 2,6-di-tert-butyl-4-methylpyridine (DBMP) in dichloromethane gives the 3-methoxy ester (XVIII), which is selectively hydroxylated with BH3, H2O2 and NaOH to (1R,3R,4R)-4-hydroxy-3-methoxycyclohexanecarboxylic acid methyl ester (XIX). The protection of (XIX) with triisopropylsilyl (TIPS) trifluoromethanesulfonate (XX) and triethylamine in dichloromethane affords the protected ester (XXI), which is reduced with dibutylaluminum hydride (DIBAL) in hexane to the corresponding aldehyde (XXII). Finally, this compound is condensed with the N-tert-butylimine of 2-(triethylsilyl)propanol (XXIII) by means of butyllithium in THF to afford the desired aldehyde (I) (Scheme 2). Allenyl stannane (II): The silylation of (R)-methyl lactate (XXIV) with tert-butyldimethylsilyl chloride (TBS-Cl) and imidazole in DMF gives the silyl ether (XXV), which is reduced with DIBAL to the corresponding aldehyde (XXVI). The reaction of (XXVI) with tetrabromomethane and triphenylphosphine in dichloromethane affords 3(R)-(tert-butyldimethysilyloxy)-1,1-dibromo-1-butene (XXVII), which by reaction with butyllithium and formaldehyde is converted to the corresponding 2-pentyn-1-ol (XXVIII). The esterification of (XXVIII) with pivaloyl (PIV) chloride and NaHCO3 in dichloromethane yields the pivaloyl ester (XXIX), which is desilylated with tetrabutylammonium fluoride (TBAF) in THF, giving the hydroxy ester (XXX). The mesylation of (XXX) with methanesulfonyl chloride and triethylamine in dichloromethane affords the sulfonate (XXXI), which is finally treated with the lithium derivative of tributylstannyl hydride, CuBr and dimethylsulfide in THF to afford the desired allenyl stannane (II).
| 【1】 Marshall, J.A.; Xie, S.P.; Synthesis of a C22-34 subunit of the immunosuppressant FK-506. J Org Chem 1995, 60, 22, 7230. |
| 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) | 11569 | 2-(tributylstannyl)-2,3-pentadienyl pivalate | C22H42O2Sn | 详情 | 详情 | |
| (XXIV) | 11591 | methyl (2R)-2-hydroxypropanoate | 17392-83-5 | C4H8O3 | 详情 | 详情 |
| (XXV) | 11592 | methyl (2R)-2-[[tert-butyl(dimethyl)silyl]oxy]propanoate | C10H22O3Si | 详情 | 详情 | |
| (XXVI) | 11593 | (2R)-2-[[tert-Butyl(dimethyl)silyl]oxy]propanal | C9H20O2Si | 详情 | 详情 | |
| (XXVII) | 11594 | tert-Butyl(dimethyl)silyl (1R)-3,3-dibromo-1-methyl-2-propenyl ether; tert-Butyl[[(1R)-3,3-dibromo-1-methyl-2-propenyl]oxy]dimethylsilane | C10H20Br2OSi | 详情 | 详情 | |
| (XXVIII) | 11595 | (4R)-4-[[tert-Butyl(dimethyl)silyl]oxy]-2-pentyn-1-ol | C11H22O2Si | 详情 | 详情 | |
| (XXIX) | 11596 | (4R)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-pentynyl pivalate | C16H30O3Si | 详情 | 详情 | |
| (XXX) | 11597 | (4R)-4-hydroxy-2-pentynyl pivalate | C10H16O3 | 详情 | 详情 | |
| (XXXI) | 11598 | (4R)-4-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-2-pentynyl pivalate | C13H22O3S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)This compound can be obtained by two related ways: 1) The condensation of 2-O-(p-toluenesulfonyl)-D-lactoyl chloride (IV) with 1-methyl-2-oxoimidazolidine-4(S)-carboxylic acid tert-butyl ester (VIII) by means of potassium tert-butoxide in THF gives 1-methyl-2-oxo-3-[2(R)-(p-toluenesulfonyloxy)propionyl]imidazolidine-4(S)-carboxylic acid tert-butyl ester (IX), which is then condensed with 2(S)-amino-4-phenylbutyric acid ethyl ester (X) by means of triethylamine in DMSO yielding 3-[N-[1(S)-(ethoxycarbonyl)-3-phenylpropyl]-L-alanyl]-1-methyl-2-oxoimidazolidine-4(S)-carboxylic acid tert-butyl ester (XI). Finally, this compound is hydrolyzed with HCl in dioxane - water. The starting compounds (IV) and (VIII) are obtained as follows: a) The condensation of D-lactic acid methyl ester with p-toluenesulfonyl chloride and triethylamine gives the corresponding sulfonate (II), which is hydrolyzed with NaOH to the free acid (III). Finally, this compound is treated with refluxing SOCl2 to give acid chloride (IV). b) The esterification of 3-(benzyloxycarbonyl)-2-oxoimidazolidine-4(S)-carboxylic acid (V) with tert-butanol gives the corresponding ester (VI), which is methylated with methyl iodide and K2CO3 to 3-(benzyloxycarbonyl)-1-methyl-2-oxoimidazolidine-4(S)-carboxylic acid tert-butyl ester (VII). This compound is debenzylated by hydrogenation with H2 over Pd/C to afford imidazolidine ester (VIII). 2) The condensation of 2(S)-bromo-4-phenylbutyric acid ethyl ester (XII) with L-alanine benzyl ester (XIII) by means of K2CO3 in DMSO gives N-[1(S)-(ethoxycarbonyl)-3-phenylpropyl]-L-alanine benzyl ester (XIV), which is debenzylated by hydrogenation as before yielding the free acid (XV). The esterification of (XV) with N-hydroxysuccinimide gives the corresponding active ester (XVI), which is finally condensed with imidazolidine ester (VIII) by means of potassium tert-butoxide to afford the precursor (XI) already obtained.
| 【1】 Yoneda, N.; Kato, S.; Hayashi, K.; Ochiai, K. (Tanabe Seiyaku Co., Ltd.); Agents for the treatment of hypertension. JP 1985013715 . |
| 【2】 Yoneda, N.; Kato, J.; Hayashi, K.; Ochiani, T.; Kinashi, K. (Tanabe Seiyaku Co., Ltd.); Quinolinecarboxylic acid derivs. and method for their preparation. EP 0095163; ES 8603427; US 4508727 . |
| 【3】 Hayashi, K.; Kubota, H. (Tanabe Seiyaku Co., Ltd.); Process for preparing optically active 2-oxoimidazolidine derivs. EP 0373881 . |
| 【4】 Kato, J.; Hayashi, K.; Ishida, R.; Yoneda, N.; Ochiai, T.; Kubo, M.; Nunami, K.-I.; Studies on angiotensin converting enzyme inhibitors. 4. Synthesis and angiotensin converting enzyme inhibitory activities of 3-acyl-1-alkyl-2-oxoimidazolidine-4-carboxylic acid derivatives. J Med Chem 1989, 32, 2, 289. |
| 【5】 Hayashi, K.; Kubota, H.; Yamagishi, M.; Nunami, K.-I.; Nishimoto, S.; Studies on angiotensin converting enzyme inhibitors. V. The diastereoselective synthesis of 2-oxoimidazolidine derivatives. Chem Pharm Bull 1991, 39, 6, 1374. |
| 【6】 Prous, J.; Castaner, J.; Imidapril Hydrochloride. Drugs Fut 1992, 17, 7, 551. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 10264 | 1-Hydroxydihydro-1H-pyrrole-2,5-dione; N-Hydroxysuccinimide; 1-Hydroxy-2,5-pyrrolidinedione | 6066-82-6 | C4H5NO3 | 详情 | 详情 | |
| (I) | 11591 | methyl (2R)-2-hydroxypropanoate | 17392-83-5 | C4H8O3 | 详情 | 详情 |
| (II) | 15653 | Methyl (2S)-2-{[(4-methylphenyl)sulfonyl]oxy}propanoate | C11H14O5S | 详情 | 详情 | |
| (III) | 15654 | (2R)-2-[[(4-methylphenyl)sulfonyl]oxy]propionic acid | C10H12O5S | 详情 | 详情 | |
| (IV) | 15655 | (1R)-2-chloro-1-methyl-2-oxoethyl 4-methylbenzenesulfonate | C10H11ClO4S | 详情 | 详情 | |
| (V) | 15656 | (4S)-3-[(benzyloxy)carbonyl]-2-oxotetrahydro-1H-imidazole-4-carboxylic acid | C12H12N2O5 | 详情 | 详情 | |
| (VI) | 15657 | 1-benzyl 5-(tert-butyl) (5S)-2-oxotetrahydro-1H-imidazole-1,5-dicarboxylate | C16H20N2O5 | 详情 | 详情 | |
| (VII) | 15658 | 1-benzyl 5-(tert-butyl) (5S)-3-methyl-2-oxotetrahydro-1H-imidazole-1,5-dicarboxylate | C17H22N2O5 | 详情 | 详情 | |
| (VIII) | 15659 | tert-butyl (4S)-1-methyl-2-oxotetrahydro-1H-imidazole-4-carboxylate | C9H16N2O3 | 详情 | 详情 | |
| (IX) | 15660 | tert-butyl (4S)-1-methyl-3-((2R)-2-[(4-methylphenyl)sulfonyl]propanoyl)-2-oxotetrahydro-1H-imidazole-4-carboxylate | C19H26N2O7S | 详情 | 详情 | |
| (X) | 15661 | ethyl (2S)-2-amino-4-phenylbutanoate | C12H17NO2 | 详情 | 详情 | |
| (XI) | 15662 | tert-butyl (4S)-3-((2S)-2-[[(1S)-1-(ethoxycarbonyl)-3-phenylpropyl]amino]propanoyl)-1-methyl-2-oxotetrahydro-1H-imidazole-4-carboxylate | C24H35N3O6 | 详情 | 详情 | |
| (XII) | 15663 | ethyl (2S)-2-bromo-4-phenylbutanoate | C12H15BrO2 | 详情 | 详情 | |
| (XIII) | 10898 | benzyl (2R)-2-aminopropanoate | C10H13NO2 | 详情 | 详情 | |
| (XIV) | 15665 | ethyl (2S)-2-[[(1S)-2-(benzyloxy)-1-methyl-2-oxoethyl]amino]-4-phenylbutanoate | C22H27NO4 | 详情 | 详情 | |
| (XV) | 11360 | (2S)-2-[[(1S)-1-(Ethoxycarbonyl)-3-phenylpropyl]amino]propionic acid; (S)-N-(1-Ethoxycarbonyl-3-phenylpropyl)-(S)-alanine | 82717-96-2 | C15H21NO4 | 详情 | 详情 |
| (XVI) | 15667 | ethyl (2S)-2-([(1S)-2-[(2,5-dioxo-1-pyrrolidinyl)oxy]-1-methyl-2-oxoethyl]amino)-4-phenylbutanoate | C19H24N2O6 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(I)Methylation of methyl (+)-lactate (I) followed by thioacetylation and acidic hydrolysis affords (-)-thiolactic acid (IV). Reaction of 3-pyridinecarboxyaldehyde (V) with methylamine in toluene under the azeotropic condition provides the imine (VI), which when condensed with (IV) affords (+)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one (VII). Treatment of (VII) with aqueous HCl/isopropanol results in the precipitation of SM-12502.
| 【1】 Koike, H.; Natsume, Y.; Tojo, S.; Morooka, S.; SM-12502. Drugs Fut 1995, 20, 2, 153. |
| 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) | 11591 | methyl (2R)-2-hydroxypropanoate | 17392-83-5 | C4H8O3 | 详情 | 详情 |
| (II) | 16679 | methyl (2R)-2-[(methylsulfonyl)oxy]propanoate | C5H10O5S | 详情 | 详情 | |
| (III) | 16680 | methyl (2S)-2-(acetylsulfanyl)propanoate | C6H10O3S | 详情 | 详情 | |
| (IV) | 16681 | (2S)-2-sulfanylpropionic acid | C3H6O2S | 详情 | 详情 | |
| (V) | 12849 | Nicotinaldehyde; 3-Pyridinecarboxaldehyde | 500-22-1 | C6H5NO | 详情 | 详情 |
| (VI) | 16683 | N-methyl-N-[(Z)-3-pyridinylmethylidene]amine; N-[(Z)-3-pyridinylmethylidene]methanamine | C7H8N2 | 详情 | 详情 | |
| (VII) | 16684 | (2R,5S)-3,5-dimethyl-2-(3-pyridinyl)-1,3-thiazolan-4-one | C10H12N2OS | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(I)The condensation of (R)-lactic acid (I) with morpholine (II) gives the corresponding morpholide (III), which is protected at the hydroxyl position with dihydropyran (IV) to yield the tetrahydropyranyl ether (V). The Grignard reaction of (V) with 2,4-difluorophenylmagnesium bromide (VI) affords the chiral 1-propanone (VII), which by a Corey's diastereoselective epoxidation with trimethylsulfoxonium iodide is converted into the oxirane (VIII). The opening of the oxirane ring of (VIII) by means of 1,2,4-triazole (IX) and NaH provides the tertiary alcohol (X), which is treated with pyridine p-toluenesulfonate to give the deprotected diol (XI) as a (2R,3R) and (2R,3S) 4:1 diastereomeric mixture, from which the desired (2R,3R)-isomer (XII) was isolated by crystallization. The reaction of (XII) with Ms-Cl and TEA, followed by cyclization with NaOMe, yields the oxirane (XIII), which is finally condensed with 7-chloroquinazolin-4(3H)-one (XIV) by means of K2CO3 in hot NMP.
| 【1】 Tasaka, A.; Tamura, N.; Matsushita, Y.; Teranishi, K.; Hayashi, R.; Okonogi, K.; Itoh, K.; Optically active antifungal azoles. I. Synthesis and antifungal activity of (2R,3R)-2-(2,4-difluorophenyl)-3-mercapto-1-(1H-1,2,4-triazol-1-yl)-2-butanol and stereoisomers. Chem Pharm Bull 1993, 41, 6, 1035-42. |
| 【2】 Bartroli Orpi, J.; Anguita Lopez, M. (J. Uriach & Cia., SA); Method for preparing pyrimidone derivs. with antifungal activity. ES 2159488; WO 0166519 . |
| 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) | 11591 | methyl (2R)-2-hydroxypropanoate | 17392-83-5 | C4H8O3 | 详情 | 详情 |
| (II) | 10388 | Morpholine | 110-91-8 | C4H9NO | 详情 | 详情 |
| (III) | 56718 | (2R)-2-hydroxy-1-(4-morpholinyl)-1-propanone | C7H13NO3 | 详情 | 详情 | |
| (IV) | 13684 | 3,4-Dihydro-2H-pyran;2,3-Dihydro-4H-pyran; 5,6-Dihydro-4H-pyran;Dihydropyran | 110-87-2 | C5H8O | 详情 | 详情 |
| (V) | 45574 | (2R)-1-(4-morpholinyl)-2-(tetrahydro-2H-pyran-2-yloxy)-1-propanone | C12H21NO4 | 详情 | 详情 | |
| (VI) | 20262 | bromo(2,4-difluorophenyl)magnesium | C6H3BrF2Mg | 详情 | 详情 | |
| (VII) | 56717 | (2S)-1-(2,4-difluorophenyl)-2-methyl-3-tetrahydro-2H-pyran-2-yl-1-propanone | C15H18F2O2 | 详情 | 详情 | |
| (VIII) | 56719 | 2-({(1R)-1-[2-(2,4-difluorophenyl)-2-oxiranyl]ethyl}oxy)tetrahydro-2H-pyran; (1R)-1-[2-(2,4-difluorophenyl)-2-oxiranyl]ethyl tetrahydro-2H-pyran-2-yl ether | C15H18F2O3 | 详情 | 详情 | |
| (IX) | 13135 | 1H-1,2,4-Triazole; 1,2,4-Triazole | 288-88-0 | C2H3N3 | 详情 | 详情 |
| (X) | 56720 | (3R)-2-(2,4-difluorophenyl)-3-(tetrahydro-2H-pyran-2-yloxy)-1-(1H-1,2,4-triazol-1-yl)-2-butanol | C17H21F2N3O3 | 详情 | 详情 | |
| (XI) | 56721 | (3R)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2,3-butanediol | C12H13F2N3O2 | 详情 | 详情 | |
| (XII) | 13106 | (2R,3R)-2-(2,4-Difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2,3-butanediol | C12H13F2N3O2 | 详情 | 详情 | |
| (XIII) | 31738 | 1-[[(2R,3S)-2-(2,4-difluorophenyl)-3-methyloxiranyl]methyl]-1H-1,2,4-triazole | C12H11F2N3O | 详情 | 详情 | |
| (XIV) | 50077 | 7-chloro-4(3H)-quinazolinone | C8H5ClN2O | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(IV)The condensation of 1-methylindole-2-carbaldehyde (I) with 2-hydroxybenzyl triphenylphosphonium bromide (II) by means of BuLi in THF gives the vinyl derivative (III), which is condensed with (R)(+)-methyl lactate (IV) by means of DEAD and PPh3 in THF yielding the chiral ether derivative (V). The reduction of the carboxylate group of (V) with DIBAL in THF affords the expected chiral propanol derivative (VI), which is cyclized with N-methylmaleimide (VII) by heating at 180 C and aromatized with DDQ giving the pyrrolocarbazole (VIII). The reaction of the hydroxy group of (VIII) with tosyl chloride and pyridine yields the corresponding tosylate (IX), which is finally condensed with dimethylamine in hot DMF.
| 【1】 Ikuina, Y.; et al.; Synthesis and structure-activity relationships of pyrrolocarbazole derivatives possessing thrombopoietic activity. 217th ACS Natl Meet (March 21 1999, Anaheim) 1999, Abst MEDI 089. |
| 【2】 Ikuina, Y.; Murakata, C.; Saitoh, Y.; Shiotsu, Y.; Iida, T.; Tamaoki, T.; Yamashita, K.; Akinaga, S. (Kyowa Hakko Kogyo Co., Ltd.); Pyrrolocarbazole derivs.. EP 0768311; US 5728709; WO 9628447 . |
| 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) | 30938 | 1-methyl-1H-indole-2-carbaldehyde | C10H9NO | 详情 | 详情 | |
| (II) | 30939 | (2-hydroxybenzyl)(triphenyl)phosphonium bromide | 70340-04-4 | C25H22BrOP | 详情 | 详情 |
| (III) | 30940 | 2-[(E)-2-(1-methyl-1H-indol-2-yl)ethenyl]phenol | C17H15NO | 详情 | 详情 | |
| (IV) | 11591 | methyl (2R)-2-hydroxypropanoate | 17392-83-5 | C4H8O3 | 详情 | 详情 |
| (V) | 30941 | methyl (2S)-2-[2-[(E)-2-(1-methyl-1H-indol-2-yl)ethenyl]phenoxy]propanoate | C21H21NO3 | 详情 | 详情 | |
| (VI) | 30942 | (2S)-2-[2-[(E)-2-(1-methyl-1H-indol-2-yl)ethenyl]phenoxy]-1-propanol | C20H21NO2 | 详情 | 详情 | |
| (VII) | 30943 | 1-methyl-1H-pyrrole-2,5-dione | 930-88-1 | C5H5NO2 | 详情 | 详情 |
| (VIII) | 30944 | 4-(2-[[(1S)-2-hydroxy-1-methylethyl]oxy]phenyl)-2,6-dimethylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione | C25H22N2O4 | 详情 | 详情 | |
| (IX) | 30945 | (2S)-2-[2-(2,6-dimethyl-1,3-dioxo-1,2,3,6-tetrahydropyrrolo[3,4-c]carbazol-4-yl)phenoxy]propyl 4-methylbenzenesulfonate | C32H28N2O6S | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(XXIV)In a related procedure, protection of methyl (R)-lactate (XXIV) as the corresponding tetrahydropyranyl ether, followed by treatment with morpholine, gave amide (XXV). Subsequent addition of 2,4-difluorophenylmagnesium bromide (XXVI) to (XXV) afforded propiophenone (XXVII), which was converted into epoxide (XXVIII) by reaction with the ylide resulting from trimethylsulfoxonium iodide. Epoxide ring opening with 1,2,4-triazole (XVI) produced the triazolyl alcohol (XXIX). After acid cleavage of the tetrahydropyranyl protecting group of (XXIX), recrystallization of the diastereomeric mixture provided diol (XXX). Mesylation of the secondary hydroxyl group of (XXX), followed by basic cyclization of the resulting hydroxy mesylate (XXXI), produced epoxide (XXXII). Epoxide (XXXII) was reacted with 2,2-diethoxyethylamine (X) in the presence of Ti(iPrO)4 to give the amino alcohol (XXXIII). Condensation of amine (XXXIII) with carbamate (IX) generated urea (XXXIV), which was then cyclized to imidazolone (XVII) in the presence of HCl. This was finally converted to the title imidazolidinone by catalytic hydrogenation as above.
| 【3】 Kitazaki, T.; Matsushita, Y.; Hosono, H.; Itoh, K.; Mitsudera, H. (Takeda Chemical Industries, Ltd.); Triazole derivs. and their production. EP 0884311 . |
| 【1】 Ichikawa, T.; Matsushita, Y.; Yamada, M.; Tasaka, A.; Yamaguchi, M.; Itoh, K.; Okonogi, K.; Kitazaki, T.; TAK-456 and the water-soluble prodrug TAK-457, new antifungal triazoles: Synthesis and in vitro antifungal activity. 40th Intersci Conf Antimicrob Agents Chemother (Sept 17 2000, Toronto) 2000, Abst F-1085. |
| 【2】 Ichikawa, T.; et al.; Optically active antifungal azoles. XI. An alternative synthetic route for 1-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-1-tetrazolyl)phenyl]-2-imidazolidinone (TAK-456) and its analog. Chem Pharm Bull 2000, 48, 12, 1947. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 45560 | phenyl 4-(1H-1,2,3,4-tetraazol-1-yl)phenylcarbamate | C14H11N5O2 | 详情 | 详情 | |
| (X) | 10331 | 2,2-Diethoxy-1-ethanamine; 2,2-Diethoxyethylamine; Aminoacetaldehyde diethyl acetal | 645-36-3 | C6H15NO2 | 详情 | 详情 |
| (XVI) | 13135 | 1H-1,2,4-Triazole; 1,2,4-Triazole | 288-88-0 | C2H3N3 | 详情 | 详情 |
| (XVII) | 45566 | 1-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-1,2,3,4-tetraazol-1-yl)phenyl]-1,3-dihydro-2H-imidazol-2-one | C22H19F2N9O2 | 详情 | 详情 | |
| (XXIV) | 11591 | methyl (2R)-2-hydroxypropanoate | 17392-83-5 | C4H8O3 | 详情 | 详情 |
| (XXV) | 45574 | (2R)-1-(4-morpholinyl)-2-(tetrahydro-2H-pyran-2-yloxy)-1-propanone | C12H21NO4 | 详情 | 详情 | |
| (XXVI) | 20262 | bromo(2,4-difluorophenyl)magnesium | C6H3BrF2Mg | 详情 | 详情 | |
| (XXVII) | 13102 | (2R)-1-(2,4-Difluorophenyl)-2-(tetrahydro-2H-pyran-2-yloxy)-1-propanone | C14H16F2O3 | 详情 | 详情 | |
| (XXVIII) | 13103 | (1R)-1-[(2R)-2-(2,4-Difluorophenyl)oxiranyl]ethyl tetrahydro-2H-pyran-2-yl ether; 2-([(1R)-1-[(2R)-2-(2,4-Difluorophenyl)oxiranyl]ethyl]oxy)tetrahydro-2H-pyran | C15H18F2O3 | 详情 | 详情 | |
| (XXIX) | 13105 | (2R,3R)-2-(2,4-Difluorophenyl)-3-(tetrahydro-2H-pyran-2-yloxy)-1-(1H-1,2,4-triazol-1-yl)-2-butanol | C17H21F2N3O3 | 详情 | 详情 | |
| (XXX) | 13106 | (2R,3R)-2-(2,4-Difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2,3-butanediol | C12H13F2N3O2 | 详情 | 详情 | |
| (XXXI) | 13107 | (1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl methanesulfonate | C13H15F2N3O4S | 详情 | 详情 | |
| (XXXII) | 13114 | 1-[[(2S,3S)-2-(2,4-Difluorophenyl)-3-methyloxiranyl]methyl]-1H-1,2,4-triazole | C12H11F2N3O | 详情 | 详情 | |
| (XXXIII) | 45572 | (2R,3R)-3-[(2,2-diethoxyethyl)amino]-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol | C18H26F2N4O3 | 详情 | 详情 | |
| (XXXIV) | 45573 | N-(2,2-diethoxyethyl)-N-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-N'-[4-(1H-1,2,3,4-tetraazol-1-yl)phenyl]urea | C26H31F2N9O4 | 详情 | 详情 |