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【结 构 式】 
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【分子编号】10395 【品名】1,1,1-Triethoxypropane; 1,1-Diethoxypropyl ethyl ether; Triethyl orthopropionate 【CA登记号】115-80-0 |
【 分 子 式 】C9H20O3 【 分 子 量 】176.256 【元素组成】C 61.33% H 11.44% O 27.23% |
合成路线1
该中间体在本合成路线中的序号：(II)The esterification of 11beta,17alpha,21-trihydroxy-6alpha-methylpregna-1,4-diene-3,20-dione (I) with triethyl orthopropionate (II) by means of pyridinium tosylate in DMF - benzene gives the corresponding cyclic diester (III), which is partially hydrolyzed with acetic acid - sodium acetate in methanol - water, yielding the 17alpha-propionyloxy derivative (IV). Finally, this compound is acetylated with acetic anhydride and pyridine.
| 【1】 Annen, K.; Petzoldt, K.; Laurent, H.; Wiechert, R.; Hofmeister, H.; Wendt, H. (Schering AG); New 6alpha-methylprednisolone derivs. their preparation and use. EP 0072547 . |
| 【2】 Naito, Y.; Sugai, S.; Kanbara, T.; Yoshida, S.; Akaboshi, S.; Ikegami, S.; Kamano, Y.; Okazaki, T:, Kajiwara, Y.; Studies on topical antiinflammatory corticosteroids. I. Syntheses and vasoconstrictive activities of 11beta,17alpha,21-trihydroxy-6alpha-methyl-1,4-pregnadiene-3,20-dione 17-ester and 17,21-diester derivatives. Chem Pharm Bull 1985, 33, 5, 1889. |
| 【3】 Prous, J.; Castaner, J.; Methylprednisolone Aceponate. Drugs Fut 1993, 18, 2, 130. |
| 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) | 10394 | Methylprednisolone | 83-43-2 | C22H30O5 | 详情 | 详情 |
| (II) | 10395 | 1,1,1-Triethoxypropane; 1,1-Diethoxypropyl ethyl ether; Triethyl orthopropionate | 115-80-0 | C9H20O3 | 详情 | 详情 |
| (III) | 10396 | 2'-Ethoxy-2'-ethyl-11-beta-hydroxy-6-alpha-methylspiro[gona-1,4-diene-17(R),4'-1,3-dioxane]3,5'-dione | C27H38O6 | 详情 | 详情 | |
| (IV) | 10397 | (6S,8S,9S,10R,11S,13S,14S,17R)-17-glycoloyl-11-hydroxy-6,10,13-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl propionate | C25H34O6 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(A)The dehydrogenation of 16alpha-methyl-11beta,17alpha,21-trihydroxypregna-1,4-diene-3,20-dione-21-acetate (I) with dichlorodicyanobenzoquinone (II) in dioxane HCl gives 16alpha-methyl-11beta,17alpha,21-trihydroxypregna-1,4,6-triene-3,20-dione-21-acetate (III), which is hydrolyzed with aqueous NaHCO3 to the corresponding free triol (IV). The reaction of (IV) with triethyl orthopropionate (A) by means of p-toluenesulfonic acid in DMSO yields 16alpha-methyl-11beta,17alpha,21-trihydroxypregna-1,4,6-triene-3,20-dione-17,21-ethylorthopropionate (V), which is hydrolyzed partially with acetic acid to 16alpha-methyl-11beta,17alpha,21-trihydroxypregna-1,4,6-triene-3,20-dione-17-propionate (VI). The acylation of (VI) with propionic anhydride affords 16alpha-methyl-11beta,17alpha,21-trihydroxypregna-1,4,6-triene-3,20-dione-17,21-dipropionate (VII), which is finally treated with dry HCl in dioxane.
| 【1】 Green, M.J.; et al. (Schering Corp.); 7alpha-Halogeno-3,20-dioxo-1,4-pregnadienes, methods for their manufacture, their use as anti-inflammatory agents, and pharmaceutical formulations useful therefor. US 4124707 . |
| 【2】 Green, M.J.; et al. (Schering Corp.); Process for the preparation of 7{60 -halogeno-3-oxo-4-dehydro steroids and novel 7{60 -halogeno derivatives produced thereby. CA 1099254; US 4076708 . |
| 【3】 Van Wagenen, B.C.; Barmore, R.M. (NPS Pharmaceuticals, Inc.); Chiral reductions of imines leading to the syntheses of optically active amines. WO 9711934 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 20095 | propionic anhydride | 123-62-6 | C6H10O3 | 详情 | 详情 | |
| (A) | 10395 | 1,1,1-Triethoxypropane; 1,1-Diethoxypropyl ethyl ether; Triethyl orthopropionate | 115-80-0 | C9H20O3 | 详情 | 详情 |
| (I) | 32645 | 2-[(8S,9S,10R,11S,13S,14S,16R,17R)-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl acetate | C24H32O6 | 详情 | 详情 | |
| (II) | 21890 | 2,3-dichloro-5,6-dicyano-1,4-benzoquinone; 4,5-dichloro-3,6-dioxo-1,4-cyclohexadiene-1,2-dicarbonitrile | 84-58-2 | C8Cl2N2O2 | 详情 | 详情 |
| (III) | 32646 | 2-[(8S,9S,10R,11S,13S,14S,16R,17R)-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-8,9,10,11,12,13,14,15,16,17-decahydro-3H-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl acetate | 13796-64-0 | C24H30O6 | 详情 | 详情 |
| (IV) | 32647 | (8S,9S,10R,11S,13S,14S,16R,17R)-17-glycoloyl-11,17-dihydroxy-10,13,16-trimethyl-8,9,10,11,12,13,14,15,16,17-decahydro-3H-cyclopenta[a]phenanthren-3-one | 13954-10-4 | C22H28O5 | 详情 | 详情 |
| (V) | 32648 | 2'-Ethoxy-2'-ethyl-11beta-hydroxy-16alpha-methylspiro[androsta-1,4,6-triene-17(R),4'-[1,3]dioxane]-3,5'-dione | 67212-72-0 | C27H36O6 | 详情 | 详情 |
| (VI) | 32649 | (8S,9S,10R,11S,13S,14S,16R,17R)-17-glycoloyl-11-hydroxy-10,13,16-trimethyl-3-oxo-8,9,10,11,12,13,14,15,16,17-decahydro-3H-cyclopenta[a]phenanthren-17-yl propionate | C25H32O6 | 详情 | 详情 | |
| (VII) | 32650 | (8S,9S,10R,11S,13S,14S,16R,17R)-11-hydroxy-10,13,16-trimethyl-3-oxo-17-[2-(propionyloxy)acetyl]-8,9,10,11,12,13,14,15,16,17-decahydro-3H-cyclopenta[a]phenanthren-17-yl propionate | 67212-74-2 | C28H36O7 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(A)The dehydrogenation of 16alpha-methyl-17alpha,21-dihydroxypregna-1,4-diene-3,11,20-trione-21-acetate (VIII) with (II) in dioxane-HCl gives 16alpha-methyl-17alpha,21-dihydroxypregna-1,4,6-triene-3,11,20-trione-21-acetate (IX), which is hydrolyzed with aqueous NaHCO3 to the corresponding free diol (X). The reaction of (X) with triethyl orthopropionate (A) as before yields 16alpha-methyl-17alpha,21-dihydroxypregna-1,4,6-triene-3,11,20-trione-17,21-ethylorthopropionate (XI), which is hydrolyzed partially with acetic acid to 16alpha-methyl-17alpha,21-dihydroxypregna-1,4,6-triene-3,11,20-trione-17-propionate (XII). The acylation of (XII) with propionic anhydride yields the corresponding dipropionate (XIII), which is treated with dry HCl in dioxane to afford 16alpha-methyl-17alpha,21-dihydroxy-7alpha-chloropregna-1,4-diene-3,11,20-trione 17,21-dipropionate (XIV). Finally, this compound is reduced with NaSH4 in methanol - THF.
| 【1】 Green, M.J.; et al. (Schering Corp.); 7alpha-Halogeno-3,20-dioxo-1,4-pregnadienes, methods for their manufacture, their use as anti-inflammatory agents, and pharmaceutical formulations useful therefor. US 4124707 . |
| 【2】 Green, M.J.; et al. (Schering Corp.); Process for the preparation of 7{60 -halogeno-3-oxo-4-dehydro steroids and novel 7{60 -halogeno derivatives produced thereby. CA 1099254; US 4076708 . |
| 【3】 Van Wagenen, B.C.; Barmore, R.M. (NPS Pharmaceuticals, Inc.); Chiral reductions of imines leading to the syntheses of optically active amines. WO 9711934 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 20095 | propionic anhydride | 123-62-6 | C6H10O3 | 详情 | 详情 | |
| (A) | 10395 | 1,1,1-Triethoxypropane; 1,1-Diethoxypropyl ethyl ether; Triethyl orthopropionate | 115-80-0 | C9H20O3 | 详情 | 详情 |
| (II) | 21890 | 2,3-dichloro-5,6-dicyano-1,4-benzoquinone; 4,5-dichloro-3,6-dioxo-1,4-cyclohexadiene-1,2-dicarbonitrile | 84-58-2 | C8Cl2N2O2 | 详情 | 详情 |
| (VIII) | 32651 | 2-[(8S,9S,10R,13S,14S,16R,17R)-17-hydroxy-10,13,16-trimethyl-3,11-dioxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl acetate | C24H30O6 | 详情 | 详情 | |
| (IX) | 32652 | 2-[(8S,9S,10R,13S,14S,16R,17R)-17-hydroxy-10,13,16-trimethyl-3,11-dioxo-8,9,10,11,12,13,14,15,16,17-decahydro-3H-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl acetate | C24H28O6 | 详情 | 详情 | |
| (X) | 32653 | (8S,9S,10R,13S,14S,16R,17R)-17-glycoloyl-17-hydroxy-10,13,16-trimethyl-9,10,12,13,14,15,16,17-octahydro-3H-cyclopenta[a]phenanthrene-3,11(8H)-dione | C22H26O5 | 详情 | 详情 | |
| (XI) | 32654 | 2'-Ethoxy-2'-ethyl-16alpha-methylspiro[androsta-1,4,6-triene-17(R),4'-[1,3]dioxane]-3,5',11-trione | C27H34O6 | 详情 | 详情 | |
| (XII) | 32655 | (8S,9S,10R,13S,14S,16R,17R)-17-glycoloyl-10,13,16-trimethyl-3,11-dioxo-8,9,10,11,12,13,14,15,16,17-decahydro-3H-cyclopenta[a]phenanthren-17-yl propionate | C25H30O6 | 详情 | 详情 | |
| (XIII) | 32656 | 2-oxo-2-[(8S,9S,10R,13S,14S,16R,17R)-10,13,16-trimethyl-3,11-dioxo-17-(propionyloxy)-8,9,10,11,12,13,14,15,16,17-decahydro-3H-cyclopenta[a]phenanthren-17-yl]ethyl propionate | C28H34O7 | 详情 | 详情 | |
| (XIV) | 32657 | (7R,8S,9S,10R,13S,14S,16R,17R)-7-chloro-10,13,16-trimethyl-3,11-dioxo-17-[2-(propionyloxy)acetyl]-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl propionate | C28H35ClO7 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(III)The intermediate pyrimidine (IV) has been obtained as follows: The reaction of 2,4,6-trichloropyrimidine (I) with pyrrolidine in THF gives 6-chloro-2,4-bis(1-pyrrolidinyl) pyrimidine (II), which is condensed with piperazine (III) in pyridine to yield 6-(1-piperazinyl)-2,4-bis(1-pyrrolidinyl)pyrimidine (IV). The methylation of 21-acetoxy-pregna-1,4,9(11),16-tetraene-3,20-dione (V) with methylmagnesium chloride catalyzed by copper propionate, followed by hydrolysis of the acetate group with NaOMe in methanol, gives the 16-alpha-methyl steroid (VI), which is condensed with piperazine intermediate (IV) by means of MeSO2Cl and TEA in acetonitrile, affording the precursor (VII). Finally, this compound is treated with methanesulfonic acid to afford the target compound.
| 【1】 Braughler, J.M.; Hall, E.D.; Jacobsen, E.J.; McCall, J.M.; Means, E.D.; THE 21-AMINOSTEROIDS: POTENT INHIBITORS OF LIPID PEROXIDATION FOR THE TREATMENT OF CENTRAL NERVOUS SYSTEM TRAUMA AND ISCHEMIA. Drugs Fut 1989, 14, 2, 143. |
| 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) | 43734 | 2,4,6-trichloropyrimidine | 3764-01-0 | C4HCl3N2 | 详情 | 详情 |
| (II) | 43735 | 4-chloro-2,6-di(1-pyrrolidinyl)pyrimidine | 111669-15-9 | C12H17ClN4 | 详情 | 详情 |
| (III) | 10395 | 1,1,1-Triethoxypropane; 1,1-Diethoxypropyl ethyl ether; Triethyl orthopropionate | 115-80-0 | C9H20O3 | 详情 | 详情 |
| (IV) | 26075 | 4-(1-piperazinyl)-2,6-di(1-pyrrolidinyl)pyrimidine | C16H26N6 | 详情 | 详情 | |
| (V) | 43736 | 2-[(8S,10R,13S,14S)-10,13-dimethyl-3-oxo-6,7,8,10,12,13,14,15-octahydro-3H-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl acetate | 37413-91-5 | C23H26O4 | 详情 | 详情 |
| (VI) | 43737 | (8S,10R,13S,14S,16R,17S)-17-glycoloyl-10,13,16-trimethyl-6,7,8,10,12,13,14,15,16,17-decahydro-3H-cyclopenta[a]phenanthren-3-one | C22H28O3 | 详情 | 详情 | |
| (VII) | 43738 | (8S,10R,13S,14S,16R,17S)-17-(2-[4-[2,6-di(1-pyrrolidinyl)-4-pyrimidinyl]-1-piperazinyl]acetyl)-10,13,16-trimethyl-6,7,8,10,12,13,14,15,16,17-decahydro-3H-cyclopenta[a]phenanthren-3-one | C38H52N6O2 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(C)The 1alpha,3beta-diol (Ia) derived from ergosterol was used as the starting material. The alcohol (Ia) was converted to methoxymethyl derivative (Ib) by reaction with chloromethyl methyl ether (4 eq) in dichloromethane for 16 h, which was oxidized with 3 eq of N-methylmorpholine N-oxide in the presence of osmium tetroxide (0.5 eq) in tert-butanol:tetrahydrofuran:water (10:3:1) for 4 h at room temperature to afford the 22,23-diol. The resulting diol was then cleaved by sodium metaperiodate (2.5 eq) in aqueous tetrahydrofuran (5 h, room temperature) to give the 22-aldehyde (IIa) in 30% yield from (Ia). Reaction of (IIa) with 6 eq of vinyl magnesium bromide (tetrahydrofuran, 0 C to room temperature, 2 h) gave the allyl alcohol (IIb) as a mixture of C-22 diastereoisomers. The Claisen reaction of (IIb) with 10 eq of triethyl orthopropionate and a catalytic amount of propionic acid (benzene reflux, 16 h) gave gamma,delta-unsaturated ester (IIa) in 70% yield from (IIa). The lithium enolate of (IIIa) generated by lithium N-isopropylcyclohexylamide in tetrahydrofuran at -78 C was reacted with oxygen for 1 h and subsequent reduction with triethyl phosphine at -78 C gave the 25-hydroxy ester (IIIb) in 87% yield. (IIIb) was shown to be a 1:1 mixture of C-25 diastereoisomers by high-pressure liquid chromatographic (HPLC) analysis. Alkaline hydrolysis (KOH, methanol, 60 C, 2.5 h) of the ester gave the hydroxy acid (IIIc) in 87% yield. (IIIc) was treated with 6 eq of I2 in dichloromethane in the presence of pyridine (15 eq) to give the iodolactone (IVa) in 74% yield, which was separated into isomers by silica gel column chromatography in a 1.5:1 ratio.
| 【1】 Morris, D.S.; Norris, A.F.; Williams, D.H.; Structure and synthesis of 25-hydroxycholecalciferol-26,23-lactone, a metabolite of vitamin D3. J Org Chem 1981, 46, 3422-28. |
| 【2】 Seino, Y.; Ishizuka, S.; 23(S),25(R)-1alpha,25-(OH)2-D3-26,23-Lactone. Drugs Fut 1992, 17, 8, 655. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (B) | 16524 | bromo(vinyl)magnesium | 1826-67-1 | C2H3BrMg | 详情 | 详情 |
| (D) | 20178 | propionic acid | 79-09-4 | C3H6O2 | 详情 | 详情 |
| (Ia) | 31263 | (1S,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-[(1R,2E,4R)-1,4,5-trimethyl-2-hexenyl]-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-1,3-diol | C28H46O2 | 详情 | 详情 | |
| (A) | 31264 | 4-methylmorpholin-4-ium-4-olate | C5H11NO2 | 详情 | 详情 | |
| (Ib) | 31265 | (1S,8S,9S,10R,13R,14S,17R)-1,3-bis(methoxymethoxy)-10,13-dimethyl-17-[(1R,2E,4R)-1,4,5-trimethyl-2-hexenyl]-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene; (1S,8S,9S,10R,13R,14S,17R)-1-(methoxymethoxy)-10,13-dimethyl-17-[(1R,2E,4R)-1,4,5-trimethyl-2-hexenyl]-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl methoxymethyl ether | C32H54O4 | 详情 | 详情 | |
| (IIa) | 31266 | (2S)-2-[(1S,8S,9S,10R,13S,14S,17R)-1,3-bis(methoxymethoxy)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]propanal | C26H42O5 | 详情 | 详情 | |
| (IIb) | 31267 | (4S)-4-[(1S,8S,9S,10R,13S,14S,17R)-1,3-bis(methoxymethoxy)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]-1-penten-3-ol | C28H46O5 | 详情 | 详情 | |
| (E) | 31268 | N-Cyclohexyl-N-methylamide lithium salt | C9H18LiN | 详情 | 详情 | |
| (IIIa) | 31269 | ethyl (E,6R)-6-[(1S,8S,9S,10R,13R,14S,17R)-1,3-bis(methoxymethoxy)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-methyl-4-heptenoate | C33H54O6 | 详情 | 详情 | |
| (IIIb) | 31270 | ethyl (E,6R)-6-[(1S,8S,9S,10R,13R,14S,17R)-1,3-bis(methoxymethoxy)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-hydroxy-2-methyl-4-heptenoate | C33H54O7 | 详情 | 详情 | |
| (IIIc) | 31271 | (E,6R)-6-[(1S,8S,9S,10R,13R,14S,17R)-1,3-bis(methoxymethoxy)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-hydroxy-2-methyl-4-heptenoic acid | C31H50O7 | 详情 | 详情 | |
| (IVa) | 31272 | 5-[(2S)-2-[(1S,8S,9S,10R,13S,14S,17R)-1,3-bis(methoxymethoxy)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]-1-iodopropyl]-3-hydroxy-3-methyldihydro-2(3H)-furanone | C31H49IO7 | 详情 | 详情 | |
| (C) | 10395 | 1,1,1-Triethoxypropane; 1,1-Diethoxypropyl ethyl ether; Triethyl orthopropionate | 115-80-0 | C9H20O3 | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(XI)A stereoselective synthesis of beta-elemene has been reported: Reaction of 2-allylpropane-1,3-diol (I) with tosyl chloride and pyridine gives the ditosylate (II), which is treated with NaCN in refluxing DMF to yield the dinitrile (III). The methanolysis of (III) with TsOH and refluxing methanol affords the dicarboxylic acid (IV), which is reduced with LiAlH4 in THF providing 3-allyl-1,5-pentanediol (V). The reaction of (V) with CBr4 and PPh3 in dichloromethane gives the dibromide (VI), which is ozonolyzed with ozone and PPh3 in dichloromethane to yield the aldehyde (VII). Condensation of (VII) with the phosphorane (VIII) in dichloromethane affords the unsaturated ester (IX), which is reduced with DIBAL in toluene to afford alcohol (X). Condensation of (X) with triethyl orthopropionate (XI) in refluxing phenol/toluene gives the anti-dibromoester (XII), along with some syn-isomer that is easily separated. Cyclization of (XII) with LDA in THF yields the cyclohexanecarboxylate (XIII), which is treated with t-BuOK in THF to afford the divinylcylohexanecarboxylate (XIV). Reduction of (XV) with DIBAL in toluene provides the carbinol (XV), which is treated with CuCl, PdCl2 and O2 in DMF/water giving the acetyl derivative (XVI). Oxidation of (XVI) with PCC and AcONa in dichloromethane gives keto-aldehyde (XVII), which is finally submitted to a double Wittig methylenation with methylenetriphenylphosphorane (XVIII) in THF.
| 【1】 Lee, J.; Kim, S.; Kim, D.; Chang, J.; Stereoselective synthesis of (±)-beta-elemene by a doubly diastereodifferentiating internal alkylation: A remarkable difference in the rate of enolization between syn and anti esters. Tetrahedron 2001, 57, 7, 1247. |
| 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) | 45745 | 2-allyl-1,3-propanediol | C6H12O2 | 详情 | 详情 | |
| (II) | 45746 | 2-([[(4-methylphenyl)sulfonyl]oxy]methyl)-4-pentenyl 4-methylbenzenesulfonate | C20H24O6S2 | 详情 | 详情 | |
| (III) | 45747 | 3-allylpentanedinitrile | C8H10N2 | 详情 | 详情 | |
| (IV) | 45748 | dimethyl 3-allylpentanedioate | C10H16O4 | 详情 | 详情 | |
| (V) | 45749 | 3-allyl-1,5-pentanediol | C8H16O2 | 详情 | 详情 | |
| (VI) | 45750 | 6-bromo-4-(2-bromoethyl)-1-hexene | C8H14Br2 | 详情 | 详情 | |
| (VII) | 45751 | 5-bromo-3-(2-bromoethyl)pentanal | C7H12Br2O | 详情 | 详情 | |
| (VIII) | 37071 | ethyl 2-(triphenylphosphoranylidene)propanoate | 5717-37-3 | C23H23O2P | 详情 | 详情 |
| (IX) | 45752 | ethyl (E)-7-bromo-5-(2-bromoethyl)-2-methyl-2-heptenoate | C12H20Br2O2 | 详情 | 详情 | |
| (X) | 45753 | (E)-7-bromo-5-(2-bromoethyl)-2-methyl-2-hepten-1-ol | C10H18Br2O | 详情 | 详情 | |
| (XI) | 10395 | 1,1,1-Triethoxypropane; 1,1-Diethoxypropyl ethyl ether; Triethyl orthopropionate | 115-80-0 | C9H20O3 | 详情 | 详情 |
| (XII) | 45754 | ethyl (2R,3R)-3-[4-bromo-2-(2-bromoethyl)butyl]-2,4-dimethyl-4-pentenoate | C15H26Br2O2 | 详情 | 详情 | |
| (XIII) | 45755 | ethyl (1R,2S,4R)-4-(2-bromoethyl)-2-isopropenyl-1-methylcyclohexanecarboxylate | 74181-34-3 | C15H25BrO2 | 详情 | 详情 |
| (XIV) | 45756 | ethyl (1R,2S,4R)-2-isopropenyl-1-methyl-4-vinylcyclohexanecarboxylate | C15H24O2 | 详情 | 详情 | |
| (XV) | 45757 | [(1R,2S,4R)-2-isopropenyl-1-methyl-4-vinylcyclohexyl]methanol | C13H22O | 详情 | 详情 | |
| (XVI) | 45758 | 1-[(1R,3S,4R)-4-(hydroxymethyl)-3-isopropenyl-4-methylcyclohexyl]-1-ethanone | C13H22O2 | 详情 | 详情 | |
| (XVII) | 45759 | (1R,2S,4R)-4-acetyl-2-isopropenyl-1-methylcyclohexanecarbaldehyde | C13H20O2 | 详情 | 详情 | |
| (XVIII) | 27301 | methylene(triphenyl)phosphorane | C19H17P | 详情 | 详情 |
合成路线7
该中间体在本合成路线中的序号：(I)Reaction of triethyl orthopropionate (I) with malononitrile (II) at reflux temperature provided (1-ethoxypropylidene)malononitrile (III). Cyclopentanone (IV) was condensed with tert-butyl carbazate (V) to afford the corresponding hydrazone (VI). Subsequent reduction with sodium cyanoborohydride, followed by acid deprotection furnished cyclopentylhydrazine (VII). Then, condensation of (VII) with malononitrile derivative (III) produced pyrazole (VIII). Partial hydrolysis of the cyano group of (VIII) using concentrated sulfuric acid gave carboxamide (IX).
| 【1】 Bacon, E.R.; Singh, B.; Lesher, G.Y.; Lesher, L.E. (Sanofi-Synthelabo); 6-Heterocyclyl pyrazolo[3,4-d]pyrimidin-4-ones and compsns. and method of use. US 5294612 . |
| 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) | 10395 | 1,1,1-Triethoxypropane; 1,1-Diethoxypropyl ethyl ether; Triethyl orthopropionate | 115-80-0 | C9H20O3 | 详情 | 详情 |
| (II) | 12061 | Malononitrile | 109-77-3 | C3H2N2 | 详情 | 详情 |
| (III) | 26907 | 2-(1-ethoxypropylidene)malononitrile | C8H10N2O | 详情 | 详情 | |
| (IV) | 15113 | cyclopentanone | 120-92-3 | C5H8O | 详情 | 详情 |
| (V) | 10893 | tert-butyl 1-hydrazinecarboxylate; tert-butyl carbazate | 870-46-2 | C5H12N2O2 | 详情 | 详情 |
| (VI) | 26908 | tert-butyl 2-cyclopentylidene-1-hydrazinecarboxylate | C10H18N2O2 | 详情 | 详情 | |
| (VII) | 26909 | 1-cyclopentylhydrazine | C5H12N2 | 详情 | 详情 | |
| (VIII) | 26910 | 5-amino-1-cyclopentyl-3-ethyl-1H-pyrazole-4-carbonitrile | C11H16N4 | 详情 | 详情 | |
| (IX) | 26911 | 5-amino-1-cyclopentyl-3-ethyl-1H-pyrazole-4-carboxamide | C11H18N4O | 详情 | 详情 |