|
【结 构 式】 
|
【分子编号】17190 【品名】potassium ethanethioate 【CA登记号】10387-40-3 |
【 分 子 式 】C2H3KOS 【 分 子 量 】114.20952 【元素组成】C 21.03% H 2.65% K 34.23% O 14.01% S 28.08% |
合成路线1
该中间体在本合成路线中的序号：Halogenation of allylamine (I) with either bromine or sulfuryl chloride produced the corresponding (halomethyl)aziridines (II). Subsequent treatment of (II) with n-butyllithium at -78 C yielded 1-azabicyclobutane (III). Opening of the bicyclic system of (III) with formic acid followed by acid hydrolysis provided 3-hydroxyazetidine (IV). This was condensed with 2-(methylsulfanyl)thiazoline (V) to give thiazolinylazetidine (VI). Alternatively, 3-hydroxyazetidine (IV) was condensed with 2-chloroethyl isothiocyanate (VII) to give the intermediate thiourea (VIII), which cyclized to the thiazoline (VI). Conversion of the hydroxyl group of (VI) into the thioacetate (IX) was carried out by either coupling with thioacetic acid under Mitsunobu conditions or by conversion to mesylate (X) followed by displacement with potassium thioacetate. The required thiol (XI) was then obtained from (IX) by basic hydrolysis of the thioacetate ester.
| 【1】 Satoh, C.; Mihira, A.; Yamamoto, S.; Hayashi, K.; Kitamura, M.; Tamai, S.; Abe, T.; Kumagai, T.; Hikida, M.; L-084, a new oral carbapenem: Synthesis and structure-activity relationships of C2-substituted 1beta-methylcarbapenems. 38th Intersci Conf Antimicrob Agents Chemother (Sept 24 1998, San Diego) 1998, Abst F-64. |
| 【2】 Abe, T.; Isoda, T.; Sato, C.; Mihira, A.; Tamai, S.; Kumagai, T. (Lederle (Japan), Ltd.); 2-(1-(1,3-Thiazolin-2-yl)azetidin-3-yl)thio-carbapenem derivs.. EP 0632039; EP 0717042; JP 1996053453; US 5534510; US 5659043; US 5783703 . |
| 【3】 Abe, T.; Kumagai, T. (Lederle (Japan), Ltd.); Carbapenem-3-carboxylic acid ester derivs.. EP 0808315; JP 1999504039; US 5886172; WO 9721712 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 12893 | Ethanethioic S-acid | C2H4OS | 详情 | 详情 | ||
| 17190 | potassium ethanethioate | 10387-40-3 | C2H3KOS | 详情 | 详情 | |
| (IIa) | 31394 | 2-(chloromethyl)aziridine | C3H6ClN | 详情 | 详情 | |
| (IIb) | 31395 | 2-(bromomethyl)aziridine | C3H6BrN | 详情 | 详情 | |
| (I) | 13672 | Allylamine; 2-Propen-1-amine | 107-11-9 | C3H7N | 详情 | 详情 |
| (III) | 31396 | 1-azabicyclo[1.1.0]butane | C3H5N | 详情 | 详情 | |
| (IV) | 31397 | 3-azetidinol | C3H7NO | 详情 | 详情 | |
| (V) | 31398 | 2-(methylsulfanyl)-4,5-dihydro-1,3-thiazole; 4,5-dihydro-1,3-thiazol-2-yl methyl sulfide | 19975-56-5 | C4H7NS2 | 详情 | 详情 |
| (VI) | 31399 | 1-(4,5-dihydro-1,3-thiazol-2-yl)-3-azetidinol | C6H10N2OS | 详情 | 详情 | |
| (VII) | 31400 | 2-chloroethyl isothiocyanate; 1-chloro-2-isothiocyanatoethane | 6099-88-3 | C3H4ClNS | 详情 | 详情 |
| (VIII) | 31401 | N-(2-chloroethyl)-3-hydroxy-1-azetidinecarbothioamide | C6H11ClN2OS | 详情 | 详情 | |
| (IX) | 31402 | S-[1-(4,5-dihydro-1,3-thiazol-2-yl)-3-azetidinyl] ethanethioate | C8H12N2OS2 | 详情 | 详情 | |
| (X) | 31403 | 1-(4,5-dihydro-1,3-thiazol-2-yl)-3-azetidinyl methanesulfonate | C7H12N2O3S2 | 详情 | 详情 | |
| (XI) | 31404 | 1-(4,5-dihydro-1,3-thiazol-2-yl)-3-azetidinylhydrosulfide; 1-(4,5-dihydro-1,3-thiazol-2-yl)-3-azetidinethiol | 179337-57-6 | C6H10N2S2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(III)1) The mesylation of 4(S)-hydroxypyrrolidin-2-one (I) with mesyl chloride and triethylamine in pyridine gives the corresponding ester (II), which is treated with potassium thioacetate (III) in refluxing acetonitrile yielding 4(R)-(acetylsulfanyl)pyrrolidin-2-one (IV). The hydrolysis of (IV) with sodium methoxide in methanol followed by acidification with aqueous HCl affords 4(R)-sulfanylpyrrolidin-2-one (V), which is condensed with (1R,5S,6S)-2-(diphenoxyphosphoryloxy)-6-[1(R)-hydroxyethyl]-1-methyl-1-carba-2-penem-3-carboxylic acid p-nitrobenzyl ester (VI) by means of ethyldiisopropylamine in acetonitrile to give (1R,5S,6S)-6-[1(R)-hydroxyethyl]-1-methyl-2-[5-oxopyrrolidin-3(R)-ylsulfanyl]-1-carba-2-penem-3-carboxylic acid p-nitrobenzyl ester (VII). The hydrogenolysis of (VII) with H2 over Pd/C in THF/aqueous phosphate buffer yields the sodium salt (VIII), which is finally esterified with pivaloyloxymethyl iodide (IX) in dimethylacetamide.
| 【1】 Yasuda, H.; Kuwahara, S.; Kawamoto, I.; Miyauchi, M.; Endo, R.; Hisaoka, M.; CS-834, a new oral carbapenem: I. Structure-activity relationships of 2-substituted 1beta-methylcarbapenems. 36th Intersci Conf Antimicrob Agents Chemother (Sept 15-18, New Orleans) 1996, Abst F105. |
| 【2】 Endo, R.; Yasuda, H.; Kawamoto, I.; Hisaoka, M.; Miyauchi, M.; Synthesis and structure-activity relationships of a novel oral carbapenem, CS-834. J Antibiot 1997, 50, 5, 429-39. |
| 【3】 Graul, A.; Castañer, R.M.; Castañer, J.; Leeson, P.; CS-834. Drugs Fut 1998, 23, 3, 261. |
| 【4】 Kawamoto, I.; Tanaka, T.; Endo, R.; Miyauchi, M.; Iwata, M. (Sankyo Co., Ltd.); 2-(Heterocyclylthio)carbapenem derivs. their preparation and their use as antibiotics. AU 8932386; EP 0337637; EP 0597821; JP 1990028180; JP 1990049783; US 5104867; US 5242914 . |
| 【5】 Kawamoto, I.; Miyauchi, M.; Endo, R. (Sankyo Co., Ltd.); Crystalline carbapenem deriv. EP 0599512; JP 1995165759 . |
| 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) | 17188 | (S)-4-hydroxy-2-pyrrolidone; (4S)-4-hydroxytetrahydro-2H-pyrrol-2-one; (S)-4-hydroxypyrrolidone | 68108-18-9 | C4H7NO2 | 详情 | 详情 |
| (II) | 17189 | (3S)-5-oxotetrahydro-1H-pyrrol-3-yl methanesulfonate | C5H9NO4S | 详情 | 详情 | |
| (III) | 17190 | potassium ethanethioate | 10387-40-3 | C2H3KOS | 详情 | 详情 |
| (IV) | 17191 | S-[(3R)-5-oxotetrahydro-1H-pyrrol-3-yl] ethanethioate | C6H9NO2S | 详情 | 详情 | |
| (V) | 17192 | (4R)-4-sulfanyltetrahydro-2H-pyrrol-2-one | 157429-42-0 | C4H7NOS | 详情 | 详情 |
| (VI) | 13224 | 4-nitrobenzyl (4R,5R,6S)-3-[(diphenoxyphosphoryl)oxy]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | 90776-59-3 | C29H27N2O10P | 详情 | 详情 |
| (VII) | 17194 | 4-nitrobenzyl (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-[[(3R)-5-oxotetrahydro-1H-pyrrol-3-yl]sulfanyl]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | C21H23N3O7S | 详情 | 详情 | |
| (VIII) | 17195 | sodium (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-[[(3R)-5-oxopyrrolidinyl]sulfanyl]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | C14H17N2NaO5S | 详情 | 详情 | |
| (IX) | 11159 | iodomethyl pivalate | C6H11IO2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：Halogenation of allylamine (I) with either bromine or sulfuryl chloride produced the corresponding (halomethyl)aziridines (II). Subsequent treatment of (II) with n-butyllithium at -78 C yielded 1-azabicyclobutane (III). Opening of the bicyclic system of (III) with formic acid followed by acid hydrolysis provided 3-hydroxyazetidine (IV). This was condensed with 2-(methylsulfanyl)thiazoline (V) to give thiazolinylazetidine (VI). Alternatively, 3-hydroxyazetidine (IV) was condensed with 2-chloroethyl isothiocyanate (VII) to give the intermediate thiourea (VIII), which cyclized to the thiazoline (VI). Conversion of the hydroxyl group of (VI) into the thioacetate (IX) was carried out by either coupling with thioacetic acid under Mitsunobu conditions or by conversion to mesylate (X) followed by displacement with potassium thioacetate. The required thiol (XI) was then obtained from (IX) by basic hydrolysis of the thioacetate ester.
| 【1】 Satoh, C.; Mihira, A.; Yamamoto, S.; Hayashi, K.; Kitamura, M.; Tamai, S.; Abe, T.; Kumagai, T.; Hikida, M.; L-084, a new oral carbapenem: Synthesis and structure-activity relationships of C2-substituted 1beta-methylcarbapenems. 38th Intersci Conf Antimicrob Agents Chemother (Sept 24 1998, San Diego) 1998, Abst F-64. |
| 【2】 Abe, T.; Isoda, T.; Sato, C.; Mihira, A.; Tamai, S.; Kumagai, T. (Lederle (Japan), Ltd.); 2-(1-(1,3-Thiazolin-2-yl)azetidin-3-yl)thio-carbapenem derivs.. EP 0632039; EP 0717042; JP 1996053453; US 5534510; US 5659043; US 5783703 . |
| 【3】 Abe, T.; Kumagai, T. (Lederle (Japan), Ltd.); Carbapenem-3-carboxylic acid ester derivs.. EP 0808315; JP 1999504039; US 5886172; WO 9721712 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 12893 | Ethanethioic S-acid | C2H4OS | 详情 | 详情 | ||
| 17190 | potassium ethanethioate | 10387-40-3 | C2H3KOS | 详情 | 详情 | |
| (IIa) | 31394 | 2-(chloromethyl)aziridine | C3H6ClN | 详情 | 详情 | |
| (IIb) | 31395 | 2-(bromomethyl)aziridine | C3H6BrN | 详情 | 详情 | |
| (I) | 13672 | Allylamine; 2-Propen-1-amine | 107-11-9 | C3H7N | 详情 | 详情 |
| (III) | 31396 | 1-azabicyclo[1.1.0]butane | C3H5N | 详情 | 详情 | |
| (IV) | 31397 | 3-azetidinol | C3H7NO | 详情 | 详情 | |
| (V) | 31398 | 2-(methylsulfanyl)-4,5-dihydro-1,3-thiazole; 4,5-dihydro-1,3-thiazol-2-yl methyl sulfide | 19975-56-5 | C4H7NS2 | 详情 | 详情 |
| (VI) | 31399 | 1-(4,5-dihydro-1,3-thiazol-2-yl)-3-azetidinol | C6H10N2OS | 详情 | 详情 | |
| (VII) | 31400 | 2-chloroethyl isothiocyanate; 1-chloro-2-isothiocyanatoethane | 6099-88-3 | C3H4ClNS | 详情 | 详情 |
| (VIII) | 31401 | N-(2-chloroethyl)-3-hydroxy-1-azetidinecarbothioamide | C6H11ClN2OS | 详情 | 详情 | |
| (IX) | 31402 | S-[1-(4,5-dihydro-1,3-thiazol-2-yl)-3-azetidinyl] ethanethioate | C8H12N2OS2 | 详情 | 详情 | |
| (X) | 31403 | 1-(4,5-dihydro-1,3-thiazol-2-yl)-3-azetidinyl methanesulfonate | C7H12N2O3S2 | 详情 | 详情 | |
| (XI) | 31404 | 1-(4,5-dihydro-1,3-thiazol-2-yl)-3-azetidinylhydrosulfide; 1-(4,5-dihydro-1,3-thiazol-2-yl)-3-azetidinethiol | 179337-57-6 | C6H10N2S2 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(A)Protection of alcohol (I) with TBDMSCl and imidazole gives silyl compound (II) which is N-methylated by means of NaH and MeI and then deprotected with HCl to yield derivative (III). Mesylation of (III) with MsCl in presence of Et3N followed by thioacetylation with AcSK (A) affords thioacetate (IV) which is then hydrolyzed with NaOMe to yield (V). Treatment of (VI) with diphenylphosphoryl chloride (B) and DIEA in acetonitrile yields (VII), which is then condensed with mercaptan (V) by means of DIEA in the same solvent to provide carbapenem (VIII). Deprotection of the carboxyl moiety of (VIII) by hydrogenation with H2 over Pd/C affords carboxylate (IX), which is finally esterified with pivaloyloxymethyl iodide (X) in N,N-dimethylacetamide or DMF.
| 【1】 Miyauchi, M.; Ohya, S.; Kawamoto, I.; Shibayama, T.; Kanno, O.; Synthesis and biological evaluation of new oral carbapenems with 1-methyl-5-oxopyrrolidin-3-ylthio moiety. J Antibiot 1999, 52, 10, 900. |
| 【2】 Kawamoto, I.; Tanaka, T.; Endo, R.; Miyauchi, M.; Iwata, M. (Sankyo Co., Ltd.); 2-(Heterocyclylthio)carbapenem derivs. their preparation and their use as antibiotics. AU 8932386; EP 0337637; EP 0597821; JP 1990028180; JP 1990049783; US 5104867; US 5242914 . |
| 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) | 16074 | Diphenyl phosphoryl chloride; 1,1'-Diphenylphosphoryl chloride; Chlorodiphenyl Phosphate; Diphenyl chlorophosphate; Diphenylchlorophosphate | 2524-64-3 | C12H10ClO3P | 详情 | 详情 |
| (A) | 17190 | potassium ethanethioate | 10387-40-3 | C2H3KOS | 详情 | 详情 |
| (I) | 17188 | (S)-4-hydroxy-2-pyrrolidone; (4S)-4-hydroxytetrahydro-2H-pyrrol-2-one; (S)-4-hydroxypyrrolidone | 68108-18-9 | C4H7NO2 | 详情 | 详情 |
| (II) | 41640 | (4S)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-pyrrolidinone | C10H21NO2Si | 详情 | 详情 | |
| (III) | 41641 | (4S)-4-hydroxy-1-methyl-2-pyrrolidinone | C5H9NO2 | 详情 | 详情 | |
| (IV) | 41642 | S-[(3R)-1-methyl-5-oxopyrrolidinyl] ethanethioate | C7H11NO2S | 详情 | 详情 | |
| (V) | 41643 | (4R)-1-methyl-4-sulfanyl-2-pyrrolidinone | C5H9NOS | 详情 | 详情 | |
| (VI) | 37720 | 4-nitrobenzyl (4R,5R,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3,7-dioxo-1-azabicyclo[3.2.0]heptane-2-carboxylate | C17H18N2O7 | 详情 | 详情 | |
| (VII) | 13224 | 4-nitrobenzyl (4R,5R,6S)-3-[(diphenoxyphosphoryl)oxy]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | 90776-59-3 | C29H27N2O10P | 详情 | 详情 |
| (VIII) | 41644 | 4-nitrobenzyl (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3-[[(3R)-1-methyl-5-oxopyrrolidinyl]sulfanyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | C22H25N3O7S | 详情 | 详情 | |
| (IX) | 41645 | sodium (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3-[[(3R)-1-methyl-5-oxopyrrolidinyl]sulfanyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | C15H19N2NaO5S | 详情 | 详情 | |
| (X) | 11159 | iodomethyl pivalate | C6H11IO2 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(A)Alcohol (I) is protected with TBDMSCl and imidazole to give silyl compound (II), which is N-methylated by means of NaH and MeI and then deprotected with HCl to yield derivative (III). Mitsunobu reaction of (III) with 4-nitrobenzoic acid in presence of PPh3 and DEAD, followed by ester hydrolysis with K2CO3, provides alcohol (IV). Mesylation of (IV) with MsCl in presence of Et3N, followed by thioacetylation with AcSK (A), affords thioacetate (V), which is then hydrolyzed with NaOMe to yield (VI). Treatment of (VII) with diphenylphosphoryl chloride (B) in CH3CN and DIEA in CH3CN yields (VIII), which is then condensed with mercaptan (VI) by means of DIEA in the same solvent to provide carbapenem (IX). Deprotection of the carboxyl moiety of (IX) by hydrogenation with H2 over Pd/C affords carboxylate (X), which is finally esterified with pivaloyloxymethyl iodide (XI) in N,N-dimethylacetamide or DMF.
| 【1】 Miyauchi, M.; Ohya, S.; Kawamoto, I.; Shibayama, T.; Kanno, O.; Synthesis and biological evaluation of new oral carbapenems with 1-methyl-5-oxopyrrolidin-3-ylthio moiety. J Antibiot 1999, 52, 10, 900. |
| 【2】 Kawamoto, I.; Tanaka, T.; Endo, R.; Miyauchi, M.; Iwata, M. (Sankyo Co., Ltd.); 2-(Heterocyclylthio)carbapenem derivs. their preparation and their use as antibiotics. AU 8932386; EP 0337637; EP 0597821; JP 1990028180; JP 1990049783; US 5104867; US 5242914 . |
| 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) | 16074 | Diphenyl phosphoryl chloride; 1,1'-Diphenylphosphoryl chloride; Chlorodiphenyl Phosphate; Diphenyl chlorophosphate; Diphenylchlorophosphate | 2524-64-3 | C12H10ClO3P | 详情 | 详情 |
| (A) | 17190 | potassium ethanethioate | 10387-40-3 | C2H3KOS | 详情 | 详情 |
| (I) | 17188 | (S)-4-hydroxy-2-pyrrolidone; (4S)-4-hydroxytetrahydro-2H-pyrrol-2-one; (S)-4-hydroxypyrrolidone | 68108-18-9 | C4H7NO2 | 详情 | 详情 |
| (II) | 41640 | (4S)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-pyrrolidinone | C10H21NO2Si | 详情 | 详情 | |
| (III) | 41641 | (4S)-4-hydroxy-1-methyl-2-pyrrolidinone | C5H9NO2 | 详情 | 详情 | |
| (IV) | 41648 | (4R)-4-hydroxy-1-methyl-2-pyrrolidinone | C5H9NO2 | 详情 | 详情 | |
| (V) | 41649 | S-[(3S)-1-methyl-5-oxopyrrolidinyl] ethanethioate | C7H11NO2S | 详情 | 详情 | |
| (VI) | 41650 | (4S)-1-methyl-4-sulfanyl-2-pyrrolidinone | C5H9NOS | 详情 | 详情 | |
| (VII) | 37720 | 4-nitrobenzyl (4R,5R,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3,7-dioxo-1-azabicyclo[3.2.0]heptane-2-carboxylate | C17H18N2O7 | 详情 | 详情 | |
| (VIII) | 13224 | 4-nitrobenzyl (4R,5R,6S)-3-[(diphenoxyphosphoryl)oxy]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | 90776-59-3 | C29H27N2O10P | 详情 | 详情 |
| (IX) | 41646 | 4-nitrobenzyl (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3-[[(3S)-1-methyl-5-oxopyrrolidinyl]sulfanyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | C22H25N3O7S | 详情 | 详情 | |
| (X) | 41647 | sodium (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3-[[(3S)-1-methyl-5-oxopyrrolidinyl]sulfanyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | C15H19N2NaO5S | 详情 | 详情 | |
| (XI) | 11159 | iodomethyl pivalate | C6H11IO2 | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(IX)Protection of 4-piperidone (I) with trityl chloride and TEA gives 1-tritylpiperidin-4-one (II), which is condensed with ethyl 2-oxoacetate (III) by means of pyrrolidine in refluxing benzene to yield 3-(ethoxycarbonylmethylene)-1-tritylpiperidin-4-one (IV). The deprotection and simultaneous reduction of compound (IV) with NaBH4 in methanol affords the 4-hydroxypiperidine derivative (V), which is condensed with 2-bromo-1-cyclopropyl-2-(2-fluorophenyl)ethanone (VI) by means of K2CO3 in DMF to provide the adduct (VII). Reaction of the OH group of (VII) with CBr4 and PPh3 in dichloromethane gives the 4-bromopiperidine derivative (VIII), which by reaction with potassium thioacetate (IX) in ethanol provides the 4-(acetylthio)piperidine derivative (X). Selective hydrolysis of compound (X) with HCl in ethanol yields the 4-sulfanylpiperidine derivative (XI), which is finally submitted to a new hydrolysis with HCl in acetic acid.
| 【1】 Castaner, J.; Mealy, N.E.; Doggrell, S.A.; CS-747 and R-99224. Drugs Fut 2001, 21, 9, 835. |
| 【2】 Asai, F.; Sugidachi, A.; Ikeda, T.; Koike, H.; Inoue, T.; Takata, K.; Iwamura, R.; Kita, J.; Yoneda, K. (Sankyo Co., Ltd.; Ube Industries, Ltd.); Cyclic amine derivs.. EP 0934928; JP 1998120649; US 6087379; WO 9808811 . |
| 【3】 Shibakawa, N.; Iwabuchi, H.; Sugidachi, A.; Ikeda, T.; Iwamura, R.; Kuroki, Y.; Inoue, T.; Asai, F. (Sankyo Co., Ltd.; Ube Industries, Ltd.); Cyclic amino cpds.. EP 1063230; WO 9943648 . |
| 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) | 27115 | 4-piperidinone | 40064-34-4 | C5H9NO | 详情 | 详情 |
| (II) | 48590 | 1-trityl-4-piperidinone | C24H23NO | 详情 | 详情 | |
| (III) | 48591 | Ethyl glyoxylate; Ethyl oxoacetate; Glyoxylic acid ethyl ester | 924-44-7 | C4H6O3 | 详情 | 详情 |
| (IV) | 48592 | ethyl 2-(4-oxo-1-trityl-3-piperidinylidene)acetate | C28H27NO3 | 详情 | 详情 | |
| (V) | 48593 | ethyl 2-(4-hydroxy-3-piperidinylidene)acetate | C9H15NO3 | 详情 | 详情 | |
| (VI) | 48584 | 2-bromo-1-cyclopropyl-2-(2-fluorophenyl)-1-ethanone | 204205-33-4 | C11H10BrFO | 详情 | 详情 |
| (VII) | 48594 | ethyl 2-[1-[2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4-hydroxy-3-piperidinylidene]acetate | C20H24FNO4 | 详情 | 详情 | |
| (VIII) | 48595 | ethyl 2-[4-bromo-1-[2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-3-piperidinylidene]acetate | C20H23BrFNO3 | 详情 | 详情 | |
| (IX) | 17190 | potassium ethanethioate | 10387-40-3 | C2H3KOS | 详情 | 详情 |
| (X) | 48596 | ethyl 2-[4-(acetylsulfanyl)-1-[2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-3-piperidinylidene]acetate | C22H26FNO4S | 详情 | 详情 | |
| (XI) | 48597 | ethyl 2-[1-[2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4-sulfanyl-3-piperidinylidene]acetate | C20H24FNO3S | 详情 | 详情 |