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【结 构 式】 
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【分子编号】10919 【品名】1-Methyl-4-piperidone; 1-Methyltetrahydro-4(1H)-pyridinone; N-Methyl-4-piperidone;1-methylpiperidin-4-one 【CA登记号】1445-73-4 |
【 分 子 式 】C6H11NO 【 分 子 量 】113.15948 【元素组成】C 63.69% H 9.8% N 12.38% O 14.14% |
合成路线1
该中间体在本合成路线中的序号：(I)The condensation of 1-methyl-4-piperidone (I) with ethyl cyanoacetate (II) in refluxing acetic acid gives ethyl (1-methyl-4-piperidylidene)cyanoacetate (III), which by reaction with KCN in ethanol is converted to ethyl (1-methyl-4-cyano-4-piperidyl)cyanoacetate (IV). The decarboxylative hydrolysis of (IV) with refluxing aqueous HCl affords (1-methyl-4-carboxy-4-piperidyl)acetic acid (V), which is esterified with ethanol - HCl to its diethyl ester (VI). Finally, this compound is treated with ethylamine at 200 C.
| 【1】 Bruschweiler, C.; Schereier, E.; Sues, R.; Winkler, H.; Improvements in or relating to Spiropiperidyl-Succinimide Derivatives. CH 411895; CH 449628; GB 1041015 . |
| 【2】 Ghose, K.; RS-86. Drugs Fut 1986, 11, 4, 276. |
| 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) | 10919 | 1-Methyl-4-piperidone; 1-Methyltetrahydro-4(1H)-pyridinone; N-Methyl-4-piperidone;1-methylpiperidin-4-one | 1445-73-4 | C6H11NO | 详情 | 详情 |
| (II) | 11877 | Cyanoacetic acid ethyl ester; Ethyl 2-cyanoacetate; Ethyl cyanoacetate; Ethyl isocyanacetate | 105-56-6 | C5H7NO2 | 详情 | 详情 |
| (III) | 24889 | ethyl 2-cyano-2-(1-methyl-4-piperidinylidene)acetate | C11H16N2O2 | 详情 | 详情 | |
| (IV) | 24890 | ethyl 2-cyano-2-(4-cyano-1-methyl-4-piperidinyl)acetate | C12H17N3O2 | 详情 | 详情 | |
| (V) | 24891 | 4-(carboxymethyl)-1-methyl-4-piperidinecarboxylic acid | C9H15NO4 | 详情 | 详情 | |
| (VI) | 24892 | ethyl 4-(2-ethoxy-2-oxoethyl)-1-methyl-4-piperidinecarboxylate | C13H23NO4 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)Reaction of 1-methyl-4-piperidone (I) with phenyllithium (II) gives 1-methyl-4-phenyl-4-piperidinol (III), which is alkylated with (IV) in NaH/DMF to yield (V), followed by reduction with hydrazine/Raney-Ni.
| 【1】 Eistetter, K.; Kley, H.-P.; Menge, H.G.; Schaefer, H. (Byk Gulden Lomberg Chemische Fabrik GmbH); Anti-depressant and analgesic 4-phenoxypiperidines. US 4333942 . |
| 【2】 Menge, H.G.; Eistetter, K.; Schaefer, H.; Kley, H.-P.; B-777-81. Drugs Fut 1983, 8, 5, 387. |
| 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) | 10919 | 1-Methyl-4-piperidone; 1-Methyltetrahydro-4(1H)-pyridinone; N-Methyl-4-piperidone;1-methylpiperidin-4-one | 1445-73-4 | C6H11NO | 详情 | 详情 |
| (II) | 24014 | Phenyllithium | 591-51-5 | C6H5Li | 详情 | 详情 |
| (III) | 24016 | 1-methyl-4-phenyl-4-piperidinol | C12H17NO | 详情 | 详情 | |
| (IV) | 14153 | 4-Fluoronitrobenzene; 1-Fluoro-4-nitrobenzene | 350-46-9 | C6H4FNO2 | 详情 | 详情 |
| (V) | 36052 | 1-methyl-4-phenyl-4-piperidinyl 4-nitrophenyl ether; 1-methyl-4-(4-nitrophenoxy)-4-phenylpiperidine | C18H20N2O3 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(II)This compound can be obtained by two related ways: 1) By cyclization of ethyl 6-chlorocoumarin-3-carboxylate (I) and N-methyl-4-piperiodone (II) by means of sodium acetate in refluxing ethanol, followed by a treatment with refluxing concentrated hydrochloric acid. 2) The cyclization of (I) and (II) by means of ammonium acetate in refluxing ethanol, followed by a treatment with cool concentrated hydrochloric acid gives the lactam od the ethyl monoester of 4a-amino-8-chloro-2-methyl-1,2,3,4,4a,10a-hexahydro(10H)-benzopyrano[3,2-c]pyrid-10-ylmalonic acid (III), which is hydrolyzed with KOH in refluxing ethanol-water to give the corresponding free acid (IV). Finally, this compound is decarboxylated by a treatment with NaHCO3 in refluxing water.
| 【1】 Baxter, M.G.; Elphick, A.R.; Miller, A.A.; Sawyer, D.A. (Glaxo Wellcome plc); 1,2,4-Triazine derivs., process for preparing such cpds., pharmaceutical compsns. and intermediates utilized for this process. CA 1133938; EP 0021121 . |
| 【2】 Castaner, J.; Prous, J.; Lortalamine. Drugs Fut 1986, 11, 5, 375. |
| 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) | 24822 | ethyl 6-chloro-2-oxo-2H-chromene-3-carboxylate | C12H9ClO4 | 详情 | 详情 | |
| (II) | 10919 | 1-Methyl-4-piperidone; 1-Methyltetrahydro-4(1H)-pyridinone; N-Methyl-4-piperidone;1-methylpiperidin-4-one | 1445-73-4 | C6H11NO | 详情 | 详情 |
| (III) | 24824 | ethyl (1S,9R,17S)-6-chloro-12-methyl-16-oxo-2-oxa-12,15-diazatetracyclo[7.5.3.0(1,10).0(3,8)]heptadeca-3,5,7-triene-17-carboxylate | C18H21ClN2O4 | 详情 | 详情 | |
| (IV) | 24825 | (1S,9R,17S)-6-chloro-12-methyl-16-oxo-2-oxa-12,15-diazatetracyclo[7.5.3.0(1,10).0(3,8)]heptadeca-3,5,7-triene-17-carboxylic acid | C16H17ClN2O4 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(II)Stobadine is obtained in a 3-step synthesis including the resolution of one of the enantiomers (V) Treatment of p-tolylhydrazine (I) with N-methyl-4-piperidone (II) yields 2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (III). After catalytic hydrogenation of (III), the (±)-cis isomer (IV) is obtained. In the following phase the resolution of (IV) is carried out with (+)-dibenzyoltartaric acid. After several recrystallizations, the optically pure (-)-cis-enantiomer is obtained. Treatment of the optically pure base with hydrochloric or another acid yields the corresponding salts.
| 【1】 Benes, L.; Stolc, S.; STOBADINE. Drugs Fut 1989, 14, 2, 135. |
| 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) | 20387 | 1-(4-methylphenyl)hydrazine | C7H10N2 | 详情 | 详情 | |
| (II) | 10919 | 1-Methyl-4-piperidone; 1-Methyltetrahydro-4(1H)-pyridinone; N-Methyl-4-piperidone;1-methylpiperidin-4-one | 1445-73-4 | C6H11NO | 详情 | 详情 |
| (III) | 20389 | 2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole | C13H16N2 | 详情 | 详情 | |
| (IV) | 20390 | (4aR,9bS)-2,8-dimethyl-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole | C13H18N2 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(XI)The reaction of 2-chloro-3,5-dinitrobenzoic acid (I) with thionil chloride, followed by treatment with diethyl ethoxymagnesium malonate gives diethyl 2-chloro-3,5-dinitrobenzoylmalonate (II), which is hydrolyzed and decarboxylated in hot sulfuric acid/propionic acid yielding 2-chloro-3,5-dinitroacetophenone (III). Reaction of (III) with thioglycolic acid by means of NaHCO3 in refluxing isopropanol gives the thioacetic acid compound (IV), which is cyclized in refluxing propionic acid yielding 3-methyl-5,7-dinitrobenzothiophene (V). Partial selective reduction of one of the nitro groups in (V) by means of ammonium sulfide in ethanol leads to 7-amino-3-methyl-5-nitrobenzothiophene (VI), which is diazotied by treatment with NaNO2 in hydrochloric acid. The following reaction with diethylamine in alkaline solution gives the triazene derivative (VII), which is finally fluorinated by reaction with anhydrous HF yielding 7-fluoro-3-methyl-5-nitrobenzothiophene (VIII). Catalytical reduction of (VIII) yields 5-amino-7-fluoro-3-methylbenzothiophene (IX), which is converted to 5-hydrazino-7-fluoro-3-methylbenzothiophene (X) by diazotation and subsequent reduction by means of stannous chloride in hydrochloric acid. The reaction of (X) with N-ethyl-4-piperidone (XI) in refluxing isopropanol gives the corresponding hydrazone, which is cyclized in refluxing isopropanol/HCl yiellding tiflucarbine base. Finally, this compound is converted to the lactate by means of lactic acid in acetone.
| 【1】 Urda, E.; Sahi, J.; Wen, Y.-H.; et al.; IXth Intl Symp Med Chem (September 14-18, Berlin) 1986, 30, 9, 977. |
| 【2】 Schollnhammer, G.; Seidel, P.-R. (Troponwerke GmbH & Co KG); 7,8,9,10-tetrahydrothieno[3,2-e]pyrido[4,3-b]indole, a process for their preparation and medicaments containing them. EP 0120439; US 4816461 . |
| 【3】 Glaser, T.; Seidel, P.-R.; Tiflucarbine. Drugs Fut 1987, 12, 6, 562. |
| 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) | 18524 | 2-sulfanylacetic acid | 68-11-1 | C2H4O2S | 详情 | 详情 |
| (A) | 28858 | diethyl ethoxymagnesiummalonate | C9H16MgO5 | 详情 | 详情 | |
| (I) | 28857 | 2-chloro-3,5-dinitrobenzoic acid | 2497-91-8 | C7H3ClN2O6 | 详情 | 详情 |
| (II) | 28859 | diethyl 2-(2-chloro-3,5-dinitrobenzoyl)malonate | C14H13ClN2O9 | 详情 | 详情 | |
| (III) | 28860 | 1-(2-chloro-3,5-dinitrophenyl)-1-ethanone | C8H5ClN2O5 | 详情 | 详情 | |
| (IV) | 28861 | 2-[(2-acetyl-4,6-dinitro-2,4-cyclohexadien-1-yl)sulfanyl]acetic acid | C10H10N2O7S | 详情 | 详情 | |
| (V) | 28862 | 3-methyl-5,7-dinitro-1-benzothiophene | C9H6N2O4S | 详情 | 详情 | |
| (VI) | 28863 | 3-methyl-5-nitro-1-benzothiophen-7-ylamine | C9H8N2O2S | 详情 | 详情 | |
| (VII) | 28864 | (E)-3,3-dimethyl-1-(3-methyl-5-nitro-1-benzothiophen-7-yl)-1-triazene | C11H12N4O2S | 详情 | 详情 | |
| (VIII) | 28865 | 7-fluoro-3-methyl-5-nitro-1-benzothiophene | C9H6FNO2S | 详情 | 详情 | |
| (IX) | 28866 | 7-fluoro-3-methyl-1-benzothiophen-5-amine | C9H8FNS | 详情 | 详情 | |
| (X) | 28867 | 1-(7-fluoro-3-methyl-1-benzothiophen-5-yl)hydrazine | C9H9FN2S | 详情 | 详情 | |
| (XI) | 10919 | 1-Methyl-4-piperidone; 1-Methyltetrahydro-4(1H)-pyridinone; N-Methyl-4-piperidone;1-methylpiperidin-4-one | 1445-73-4 | C6H11NO | 详情 | 详情 |
| (XII) | 28869 | 2-hydroxypropionic acid; Lactic acid | 50-21-5 | C3H6O3 | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(III)The synthesis of [14C]- and deuterium-labeled bisaramil hydrochloride has been reported: 1) The reduction of (14)CO2 with LiAlH4 in THF gives labeled formaldehyde (II), which by a Mannich reaction is condensed with ethylamine (IV) and N-methylpiperidin-4-one (III) by means of acetic acid in refluxing methanol to yield labeled 3-ethyl-7-methyl-3,7-diazabicyclo[3.3.1]nonan-9-one (V). The reduction of (V) with NaBH4 in methanol/NaOH affords a mixture of the alpha- and beta-isomers of the labeled 9-hydroxy derivative (VI + VII). After separation by its different solubility in isopropanol, the alpha-isomer is condensed with 4-chlorobenzoyl chloride (VIII) in hot pyridine to give [2,4-14C]-labeled bisaramil.
| 【1】 Mlinko, S.; Simon Trompler, E.; Szammer, J.; Synthesis of bisaramil labelled with carbon-14 and deuterium. J Label Compd Radiopharm 1994, 34, 4, 313. |
| 【2】 Lapis, E.; YUTAC. Drugs Fut 1985, 10, 10, 837. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (III) | 10919 | 1-Methyl-4-piperidone; 1-Methyltetrahydro-4(1H)-pyridinone; N-Methyl-4-piperidone;1-methylpiperidin-4-one | 1445-73-4 | C6H11NO | 详情 | 详情 |
| (V) | 10920 | 3-Ethyl-7-methyl-3,7-diazabicyclo[3.3.1]nonan-9-one | C10H18N2O | 详情 | 详情 | |
| (V) | 44684 | 3-ethyl-7-methyl-3,7-diazabicyclo[3.3.1]nonan-9-one | C10H18N2O | 详情 | 详情 | |
| (VI) | 10921 | 3-Ethyl-7-methyl-3,7-diazabicyclo[3.3.1]nonan-9-ol | C10H20N2O | 详情 | 详情 | |
| (VI) | 44685 | 3-ethyl-7-methyl-3,7-diazabicyclo[3.3.1]nonan-9-ol | C10H20N2O | 详情 | 详情 | |
| (VII) | 10922 | 3-Ethyl-7-methyl-3,7-diazabicyclo[3.3.1]nonan-9-ol | C10H20N2O | 详情 | 详情 | |
| (VII) | 44686 | 3-ethyl-7-methyl-3,7-diazabicyclo[3.3.1]nonan-9-ol | C10H20N2O | 详情 | 详情 | |
| (VIII) | 10295 | p-Chlorobenzoyl chloride; 4-Chlorobenzoyl chloride | 122-01-0 | C7H4Cl2O | 详情 | 详情 |
合成路线7
该中间体在本合成路线中的序号：(III)2) Hexadeuteroethyl alcohol (IX) is treated with red phosphorus and I2 at reflux temperature to give pentadeuteroethyl iodide (X), which is condensed with potassium phthalimide (XI) in DMF, yielding N-(pentadeuteroethyl)phthalimide (XII). The hydrolysis of (XII) with hydrazine and HCl affords pentadeuteroethylamine (XIII), which is condensed with 1-methylpiperidin-4-one (III) and formaldehyde (XIV) in a Mannich reaction to give 3-methyl-7-(pentadeuteroethyl)-3,7-diazabicyclo[3.3.1]nonan-9-one (XV). The reduction of (XV) with NaBH4 as before yields the diastereomeric mixture (XVI + XVII). Finally, the alpha-isomer (XVI) is condensed with 4-chlorobenzoyl chloride (VIII) as before to give the pentadeuterium-labeled bisaramil.
| 【1】 Mlinko, S.; Simon Trompler, E.; Szammer, J.; Synthesis of bisaramil labelled with carbon-14 and deuterium. J Label Compd Radiopharm 1994, 34, 4, 313. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (III) | 10919 | 1-Methyl-4-piperidone; 1-Methyltetrahydro-4(1H)-pyridinone; N-Methyl-4-piperidone;1-methylpiperidin-4-one | 1445-73-4 | C6H11NO | 详情 | 详情 |
| (VIII) | 10295 | p-Chlorobenzoyl chloride; 4-Chlorobenzoyl chloride | 122-01-0 | C7H4Cl2O | 详情 | 详情 |
| (IX) | 10924 | Ethyl alcohol; Ethanol | 1516-08-1 | C2H6O | 详情 | 详情 |
| (IX) | 44687 | Ethanol-d6 | C2H6O | 详情 | 详情 | |
| (X) | 10925 | Iodoethane;ethyl iod | 75-03-6 | C2H5I | 详情 | 详情 |
| (X) | 44688 | 1-iodoethane-d5 | C2H5I | 详情 | 详情 | |
| (XI) | 10926 | (1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)potassium | C8H4KNO2 | 详情 | 详情 | |
| (XII) | 10927 | 2-Ethyl-1H-isoindole-1,3(2H)-dione | 5022-29-7 | C10H9NO2 | 详情 | 详情 |
| (XII) | 44689 | 2-ethyl-1H-isoindole-1,3(2H)-dione | C10H9NO2 | 详情 | 详情 | |
| (XIII) | 10928 | Ethanamine | 75-04-7 | C2H7N | 详情 | 详情 |
| (XIII) | 44690 | ethylamine; 1-ethanamine | C2H7N | 详情 | 详情 | |
| (XV) | 10929 | 3-Ethyl-7-methyl-3,7-diazabicyclo[3.3.1]nonan-9-one | C10H18N2O | 详情 | 详情 | |
| (XV) | 44691 | 3-ethyl-7-methyl-3,7-diazabicyclo[3.3.1]nonan-9-one | C10H18N2O | 详情 | 详情 | |
| (XVI) | 10921 | 3-Ethyl-7-methyl-3,7-diazabicyclo[3.3.1]nonan-9-ol | C10H20N2O | 详情 | 详情 | |
| (XVI) | 44692 | 3-ethyl-7-methyl-3,7-diazabicyclo[3.3.1]nonan-9-ol | C10H20N2O | 详情 | 详情 | |
| (XVII) | 10922 | 3-Ethyl-7-methyl-3,7-diazabicyclo[3.3.1]nonan-9-ol | C10H20N2O | 详情 | 详情 | |
| (XVII) | 44693 | 3-ethyl-7-methyl-3,7-diazabicyclo[3.3.1]nonan-9-ol | C10H20N2O | 详情 | 详情 |
合成路线8
该中间体在本合成路线中的序号：(II)The reaction of N-methyl-4-piperidone (II) with phenyllithium (I) in benzene-ethyl ether below 10 C gives 4-hydroxy-1-methyl-4.phenypiperidine (III), which is dehydrated by treating with refuxing concentrated HCl.
| 【1】 Frank, M.; Clarke, H.Jr. (Novartis Corp.); Nouveaux benzomorphanes et leur preparation. DE 1445845; DE 1795599; FR 1440638; FR 4024M; GB 1050227; US 3320265 . |
| 【2】 Block, F.B.; et al. (Novartis Corp.); Certain 2,6-methano-3-benzazocines. US 3341538 . |
| 【3】 Castaner, J.; Prous, J.; MPTP. Drugs Fut 1986, 11, 5, 384. |
合成路线9
该中间体在本合成路线中的序号：(II)Naratriptan can be obtained by several related ways: 1) The reaction of 5-bromoindole (I) with 1-methylpiperidin-4-one (II) by means of KOH in methylated spirit (or methanol) at room temperature gives 5-bromo-3-(4-(hydroxy-1-methylpiperidin-4-yl)-1H-indole (III) (1, 2), which is condensed with N-methylvinylsulfonamide (IV) by means of palladium acetate and tri-p-tolyl phosphine in hot (110 C) DMF to afford (E)-N-methyl-2-[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indol-5-yl]vinylsulfonamide (V). Finally, this compound is hydrogenated with H2 over Pd/C in DMF/water/HCl, DMF/water/methanol/HCl, or water/methanesulfonic acid. 2) The reaction of indole (I) with piperidone (II) or with 4-hydroxy-1-methylpiperidine (VI) by means of KOH in refluxing methylated spirit or 1-propanol gives 5-bromo-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole (VII), which is then condensed with N-methylvinylsufonamide (IV) as before, yielding the substituted sulfonamide (V), already obtained. 3) The hydrogenation of the tetrahydropyridine (VII) with H2 over PtO2 in methanol/HCl gives 5-bromo-3-(1-methylpiperidin-4-yl)-1H-indole (VIII), which is finally condensed with N-methylvinylsulfonamide (IV) as before yielding N-methyl-2-[3-(1-methylpiperidin-4-yl)-1H-indol-5-yl]vinylsulfonamide (XI). Finally, this compound is hydrogenated with H2 over Pd/C in ethanol/DMF/HCl. 4) The reaction of 5-bromoindole (I) with sulfonamide (IV) by means of palladium acetate as before gives 2-(1H-indol-3-yl)-N-methylvinylsulfonamide (IX), which is condensed with piperidone (II) by means of refluxing KOH as before, yielding the substituted tetrahydropyridine (V), already obtained. 5) The condensation of sulfonamide (IX) with piperidone (II), by means of KOH at room temperature as before gives N-methyl-2-[3-(4-hydroxy-1-methylpiperidin-4-yl)-1H-indol-3-yl] vinylsulfonamide (X), which is dehydrated to tetrahydropyridine (V) with KOH in refluxing methylated spirit. 6) The cyclization of 2-(4-hydrazinophenyl)-N-methylethanesulfonamide (XII) with 2-(1-methylpiperidin-4-yl)acetaldehyde (XIII) by means of HCl in water. 7) The reaction of 2-(1H-indol-5-yl)-N-methylethanesulfonamide (XIV) with piperidone (II) by means of KOH in refluxing methanol, yielding N-methyl-2-[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indol-5-yl] ethylsulfonamide (XV), which is finally hydrogenated with H2 over Pd/C in ethanol/DMF.
| 【1】 Mealy, N.; Castaner, J.; Naratriptan. Drugs Fut 1996, 21, 5, 476. |
| 【2】 Oxford, A.W.; Butina, D.; Owen, M.R. (Glaxo Wellcome plc); Indole derivs. AU 8820692; EP 0303507; GB 2208646; JP 1989207288; US 4997841 . |
| 【3】 Blatcher, P.; Carter, M.; Hornby, R.; Owen, M.R. (Glaxo Wellcome plc); Process for the preparation of N-methyl-3-(1-methyl-4-piperidinyl)-1H-indole-5-ethanesulfonamide. WO 9509166 . |
| 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) | 13309 | 5-Bromo-1H-indole; 5-Bromoindole | 10075-50-0 | C8H6BrN | 详情 | 详情 |
| (II) | 10919 | 1-Methyl-4-piperidone; 1-Methyltetrahydro-4(1H)-pyridinone; N-Methyl-4-piperidone;1-methylpiperidin-4-one | 1445-73-4 | C6H11NO | 详情 | 详情 |
| (III) | 13311 | 4-(5-Bromo-1H-indol-3-yl)-1-methyl-4-piperidinol | 66306-26-9 | C14H17BrN2O | 详情 | 详情 |
| (IV) | 13312 | N-Methyl-1-ethylenesulfonamide | C3H7NO2S | 详情 | 详情 | |
| (V) | 13313 | (E)-N-Methyl-2-[3-(1-methyl-1,2,3,6-tetrahydro-4-pyridinyl)-1H-indol-5-yl]-1-ethenesulfonamide | 166306-28-1 | C17H21N3O2S | 详情 | 详情 |
| (VI) | 13314 | 4-Hydroxy-1-methylpiperidine; 1-Methyl-4-piperidinol; 4-Hydroxy-N-methylpiperidine; N-Methyl-4-hydroxypiperidine | 106-52-5 | C6H13NO | 详情 | 详情 |
| (VII) | 13315 | 5-Bromo-3-(1-methyl-1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole | 116480-53-6 | C14H15BrN2 | 详情 | 详情 |
| (VIII) | 13316 | 5-Bromo-3-(1-methyl-4-piperidinyl)-1H-indole | 66306-26-9 | C14H17BrN2 | 详情 | 详情 |
| (IX) | 13317 | (E)-2-(1H-Indol-5-yl)-N-methyl-1-ethenesulfonamide | C11H12N2O2S | 详情 | 详情 | |
| (X) | 13318 | (E)-2-[3-(4-Hydroxy-1-methyl-4-piperidinyl)-1H-indol-5-yl]-N-methyl-1-ethenesulfonamide | C17H23N3O3S | 详情 | 详情 | |
| (XI) | 13319 | (E)-N-Methyl-2-[3-(1-methyl-4-piperidinyl)-1H-indol-5-yl]-1-ethenesulfonamide | C17H23N3O2S | 详情 | 详情 | |
| (XII) | 13320 | 2-(4-Hydrazinophenyl)-N-methyl-1-ethanesulfonamide | C9H15N3O2S | 详情 | 详情 | |
| (XIII) | 13321 | 2-(1-Methyl-4-piperidinyl)acetaldehyde | C8H15NO | 详情 | 详情 | |
| (XIV) | 13322 | 2-(1H-Indol-5-yl)-N-methyl-1-ethanesulfonamide | C11H14N2O2S | 详情 | 详情 | |
| (XV) | 13323 | N-Methyl-2-[3-(1-methyl-1,2,3,6-tetrahydro-4-pyridinyl)-1H-indol-5-yl]-1-ethanesulfonamide | C17H23N3O2S | 详情 | 详情 |
合成路线10
该中间体在本合成路线中的序号：(I)YM-796 can be obtained by two different ways: 1) The Wittig condensation of 1-methylpiperidin-4-one (I) with 2-(diethoxyphosphoryl)acetic acid ethyl ester (II) by means of NaH in dimethoxyethane gives 2-(1-methylpiperidin-4-ylidene) acetic acid ethyl ester (III), which is cyclized with ethyl lactate (IV) by means of NaH in DMSO yielding 2,8-dimethyl-3-oxo-1-oxa-8-azaspiro[4.5]decane-4-carboxylic acid ethyl ester (V). The decarboxylation of (V) with refluxing aqueous 1N HCl affords 2,8-dimethyl-1-oxa-8-azaspiro[4.5]decan-3-one (VI), which is submitted to a new Wittig condensation with methyltriphenylphosphonium iodide (or bromide) (VII) by means of NaH in DMSO to give racemic 2,8-dimethyl-3-methylene-1-oxa-8-azaspiro[4.5]decane (VIII). Finally, this compound is submitted to optical resolution with L-tartaric acid or with di-p-toluoyl-D-tartaric acid. 2) The Wittig condensation of 4-oxopiperidine-1-carboxylic acid ethyl ester (IX) with phosphorane (VII) as before gives the corresponding methylene derivative (X), which is submitted to alkoxybromination with N-bromosuccinimide (NBS) and (S)-3-butyn-2-ol (XI) yielding (S)-4-(bromomethyl)-4-(1-methyl-2-propynyloxy)piperidine-1-carboxylic acid ethyl ester (XII). The radical cyclization of (XII) with NaBH4 catalyzed by bis(dimethylglyoximato)(pyridine)cobalt(III) chloride [chlorocobaloxime(III)] affords (S)-2-methyl-3-methylene-1-oxa-8-azaspiro[4.5]decane-8-carboxylic acid ethyl ester (XIII), which is finally reduced with sodium bis(2-methoxyethoxy)aluminum hydride (vitride) in toluene and treated with fumaric acid to obtain the sesquifumarate salt.
| 【1】 Ngo, J.; Martel, A.M.; Castaner, J.; YM-796. Drugs Fut 1997, 22, 2, 144. |
| 【2】 Tsukamoto, S.; Kondo, Y.; Igarashi, S.; An efficient synthesis of (S)-(-)-2,8-dimethyl-3-methylene-1-oxa-8-azaspiro[4.5]decane by cobaloxime(I)-mediated radical cyclization. Heterocycles 1995, 41, 8, 1771-1778. |
| 【3】 Tsukamoto, S.; Fujii, M.; Yasunaga, T.; Matsuda, K.; Wanibuchi, F.; Hidaka, K.; Furuya, T.; Tamura, T.; Synthesis and structure-activity studies of a series of 1-oxa-8-azaspiro[4.5]decanes as M1 muscarinic agonists. Chem Pharm Bull 1995, 43, 5, 842-852. |
| 【4】 Tsukamoto, S.-I.; Nagaoka, H.; Usuda, S.; Harada, M.; Tamura, T. (Yamanouchi Pharmaceutical Co., Ltd.); Heterocyclic spiro cpds. and their preparation. AU 8823449; EP 0311313; JP 1990036183; US 4996210 . |
| 【5】 Tsukamoto, S.; Kohinata, T.; Fujii, M.; Tomisawa, S. (Yamanouchi Pharmaceutical Co., Ltd.); (-)-(S)-2,8-Dimethyl-3-methylene-1-oxa-8-azaspiro[4,5]decane L-tartrate. EP 0590150; JP 1993508699; WO 9220683 . |
| 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) | 10919 | 1-Methyl-4-piperidone; 1-Methyltetrahydro-4(1H)-pyridinone; N-Methyl-4-piperidone;1-methylpiperidin-4-one | 1445-73-4 | C6H11NO | 详情 | 详情 |
| (II) | 10019 | Ethyl 2-(diethoxyphosphoryl)acetate; Triethyl phosphonoacetate | 867-13-0 | C8H17O5P | 详情 | 详情 |
| (III) | 13480 | ethyl 2-(1-methyl-4-piperidinylidene)acetate | C10H17NO2 | 详情 | 详情 | |
| (IV) | 13481 | ethyl lactate; ethyl 2-hydroxypropanoate | 97-64-3 | C5H10O3 | 详情 | 详情 |
| (V) | 13482 | ethyl 2,8-dimethyl-3-oxo-1-oxa-8-azaspiro[4.5]decane-4-carboxylate | C13H21NO4 | 详情 | 详情 | |
| (VI) | 13483 | 2,8-Dimethyl-1-oxa-8-azaspiro[4.5]decan-3-one | C10H17NO2 | 详情 | 详情 | |
| (VII) | 13484 | Methyl(triphenyl)phosphonium iodide; Methyltriphenylphosphonium iodide | 2065-66-9 | C19H18IP | 详情 | 详情 |
| (VIII) | 13485 | 2,8-Dimethyl-3-methylene-1-oxa-8-azaspiro[4.5]decane | C11H19NO | 详情 | 详情 | |
| (IX) | 13486 | Ethyl 4-oxo-1-piperidinecarboxylate; N-Carbethoxy-4-piperidone | 29976-53-2 | C8H13NO3 | 详情 | 详情 |
| (X) | 13487 | ethyl 4-methylene-1-piperidinecarboxylate | C9H15NO2 | 详情 | 详情 | |
| (XI) | 13488 | (2S)-3-Butyn-2-ol; (S)-(-)-3-Butyn-2-ol | 2914-69-4 | C4H6O | 详情 | 详情 |
| (XII) | 13489 | ethyl 4-(bromomethyl)-4-[[(1S)-1-methyl-2-propynyl]oxy]-1-piperidinecarboxylate | C13H20BrNO3 | 详情 | 详情 | |
| (XIII) | 13490 | ethyl (2S)-2-methyl-3-methylene-1-oxa-8-azaspiro[4.5]decane-8-carboxylate | C13H21NO3 | 详情 | 详情 |
合成路线11
该中间体在本合成路线中的序号：(II)Condensation of 5-nitroindole (I) with 1-methyl-4-piperidone (II) in the presence of KOH produced tetrahydropyridinyl indole (III). Subsequent catalytic hydrogenation of (III) over Pd/C gave the 5-amino-3-piperidinylindole (VI). In a related procedure, 5-aminoindole (IV) was condensed with piperidone (II), and the resulting tetrahydropyridine (V) was hydrogenated to yield (VI). Aminoindole (VI) was finally condensed with 4-fluorobenzoyl chloride (VII) to produce the corresponding amide, which was isolated as the fumarate salt.
| 【1】 Audia, J.E.; Dressman, B.A.; Droste, J.J.; Fritz, J.E.; Kaldor, S.W.; Koch, D.J.; Krushinski, J.H. Jr.; Nissen, J.S.; Rocco, V.P.; Schaus, J.M.; Thompson, D.C. (Eli Lilly and Company); 5-Substd.-3-(1,2,3,6-tetrahydropyridin-4-yl)- and 3-(piperidin-4-yl)-1H-indoles: New 5-HT1F agonists. EP 0733628; JP 1999502816; US 5708008; WO 9629075 . |
| 【2】 Johnson, K.W.; Phebus, L.A. (Eli Lilly and Company); Use of a serotonin 5-HT1F agonist in the manufacture of a medicament for treating or ameliorating the symptoms of common cold or allergic rhinitis. EP 0824917; US 5962473; WO 9806402 . |
| 【3】 Johnson, K.W.; Phebus, L.A. (Eli Lilly and Company); A method for the prevention of migraine. WO 9811895 . |
| 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) | 26916 | 5-Nitroindole; 5-nitro-1H-indole | 6146-52-7 | C8H6N2O2 | 详情 | 详情 |
| (II) | 10919 | 1-Methyl-4-piperidone; 1-Methyltetrahydro-4(1H)-pyridinone; N-Methyl-4-piperidone;1-methylpiperidin-4-one | 1445-73-4 | C6H11NO | 详情 | 详情 |
| (III) | 26917 | 3-(1-methyl-1,2,3,6-tetrahydro-4-pyridinyl)-5-nitro-1H-indole | C14H15N3O2 | 详情 | 详情 | |
| (IV) | 26918 | Indole-5-amine; 1H-indol-5-ylamine; 5-Aminoindole | 5192-03-0 | C8H8N2 | 详情 | 详情 |
| (V) | 26919 | 3-(1-methyl-1,2,3,6-tetrahydro-4-pyridinyl)-1H-indol-5-amine | C14H17N3 | 详情 | 详情 | |
| (VI) | 26920 | 3-(1-methyl-4-piperidinyl)-1H-indol-5-amine | C14H19N3 | 详情 | 详情 | |
| (VII) | 17263 | 4-fluorobenzoyl chloride | 403-43-0 | C7H4ClFO | 详情 | 详情 |
合成路线12
该中间体在本合成路线中的序号：(X)Condensation between 5-bromoindole (I) in ether and oxalyl chloride (II) in dichloromethane followed by treatment with dimethylamine provides N,N-dimethyaminoglyoxyl derivative (III), which is then reduced with LiAlH4 in THF to yield compound (IV). Coupling of (IV) with benzoyl chloride (V) by means of Et3N and DMAP in dichloromethane affords benzoylindole derivative (VI), which is then subjected to reaction with tributylstannyl derivative (VII) in toluene in the presence of Pd(PPh3)4 to furnish compound (VIII). Treatment of (VIII) with NaOH in refluxing MeOH gives indole (IX), which is converted into the final product by reduction with LiAlH4 in refluxing THF) and treatment with HCl for the formation of the corresponding hydrochloride salt. Alternatively, the target compound can be obtained as follows: treatment of (IV) with KH in ether and tert-butyllithium in pentane followed by reaction with N-methylpiperidinone (X) affords hydroxy derivative (XI), which is finally converted into the desired product.
| 【1】 Arora, J.; et al.; 5-Bicyclopiperidinetryptamine derivatives as selective 5-HT1D agonists. Soc Neurosci Abst 2000, 26, Part 1, Abst 145.14. |
| 【2】 Slassi, A.; Edwards, L.; Meng, Q.; Rakhit, S. (NPS Allelix Corp.); 5-Cyclo indole cpds. as 5-HT1D receptor ligands. EP 0944595; JP 2001504501; WO 9823587 . |
| 【3】 Rakhit, S.; Edwards, L.; Slassi, A.; Meng, Q. (NPS Allelix Corp.); 5-Cyclo indole cpds.. US 5998438 . |
| 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) | 13309 | 5-Bromo-1H-indole; 5-Bromoindole | 10075-50-0 | C8H6BrN | 详情 | 详情 |
| (II) | 29841 | Oxalyl chloride; 2-Chloro-2-oxoacetyl chloride | 79-37-8 | C2Cl2O2 | 详情 | 详情 |
| (III) | 40926 | 2-(5-bromo-1H-indol-3-yl)-N,N-dimethyl-2-oxoacetamide | C12H11BrN2O2 | 详情 | 详情 | |
| (IV) | 49717 | N-[2-(5-bromo-1H-indol-3-yl)ethyl]-N,N-dimethylamine; 2-(5-bromo-1H-indol-3-yl)-N,N-dimethyl-1-ethanamine | C12H15BrN2 | 详情 | 详情 | |
| (V) | 10463 | Benzoyl chloride | 98-88-4 | C7H5ClO | 详情 | 详情 |
| (VI) | 49718 | [5-bromo-3-[2-(dimethylamino)ethyl]-1H-indol-1-yl](phenyl)methanone | C19H19BrN2O | 详情 | 详情 | |
| (VII) | 49719 | tert-butyl 4-(tributylstannyl)-3,6-dihydro-1(2H)-pyridinecarboxylate | C22H43NO2Sn | 详情 | 详情 | |
| (VIII) | 49720 | tert-butyl 4-[1-benzoyl-3-[2-(dimethylamino)ethyl]-1H-indol-5-yl]-3,6-dihydro-1(2H)-pyridinecarboxylate | C29H35N3O3 | 详情 | 详情 | |
| (IX) | 49721 | tert-butyl 4-[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl]-3,6-dihydro-1(2H)-pyridinecarboxylate | C22H31N3O2 | 详情 | 详情 | |
| (X) | 10919 | 1-Methyl-4-piperidone; 1-Methyltetrahydro-4(1H)-pyridinone; N-Methyl-4-piperidone;1-methylpiperidin-4-one | 1445-73-4 | C6H11NO | 详情 | 详情 |
| (XI) | 49722 | 4-[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl]-1-methyl-4-piperidinol | C18H27N3O | 详情 | 详情 |
合成路线13
该中间体在本合成路线中的序号：(V)1-(4-Fluorophenyl)-2-(4-pyridyl)ethanone (I) was brominated in HOAc to yield bromoketone (II). Reaction of (II) with ammonium oxalate in formamide at 200 C produced a 1:1 mixture of imidazole (III) and oxazole (IV). After isolation of the desired oxazole (IV), its lithiation with n-butyllithium followed by addition to N-methyl-4-piperidinone (V) furnished the corresponding carbinol .
| 【1】 Zimmerlin, A.G.; Di Padova, F.E.; Revesz, L.; Manning, U.; Gram, H.; Hiestand, P.; Buhl, T.; Feifel, R.; SAR of 4-hydroxypiperidine and hydroxyalkyl substituted heterocycles as novel p38 MAP kinase inhibitors. Bioorg Med Chem Lett 2000, 10, 11, 1261. |
| 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) | 45005 | 1-(4-fluorophenyl)-2-(4-pyridinyl)-1-ethanone | C13H10FNO | 详情 | 详情 | |
| (II) | 45006 | 2-bromo-1-(4-fluorophenyl)-2-(4-pyridinyl)-1-ethanone | 4736-60-1 | C13H9BrFNO | 详情 | 详情 |
| (III) | 45007 | 4-[4-(4-fluorophenyl)-1,3-oxazol-5-yl]pyridine | C14H9FN2O | 详情 | 详情 | |
| (IV) | 33798 | 4-[4-(4-fluorophenyl)-1H-imidazol-5-yl]pyridine | C14H10FN3 | 详情 | 详情 | |
| (V) | 10919 | 1-Methyl-4-piperidone; 1-Methyltetrahydro-4(1H)-pyridinone; N-Methyl-4-piperidone;1-methylpiperidin-4-one | 1445-73-4 | C6H11NO | 详情 | 详情 |
合成路线14
该中间体在本合成路线中的序号：(XLI)The thiazolopyridine derivatives (II) and (III) can be obtained in several ways. Treatment of N-Boc-4-piperidinone (XXXVI) with pyrrolidine in the presence of p-TsOH·H2O in refluxing cyclohexane, followed by cyclization of the resulting enamine with cyanamide and elemental sulfur in MeOH gives 2-amino-5-Boc-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine (XXXVII), which by Sandmeyer reaction with CuBr2 and t-BuONO in DMF at 40 °C affords the 2-bromo compound (XXXVIII). After removal of the N-Boc-protecting group of intermediate (XXXVIII) with TFA, reductive methylation of the deprotected amine (XXXIX) with formaldehyde and NaBH(OAc)3 in the presence of AcOH and Et3N in CH2Cl2 yields 2-bromo-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine (XL) , optionally isolated as the corresponding tosylate salt (1). Alternatively, cyclization of 1-methyl-4-piperidinone (XLI) with cyanamide and sulfur in the presence of pyrrolidine in i-PrOH at 50 °C yields 2-amino-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine (XLII), which is converted to the corresponding bromide (XL) by diazotization with NaNO2 in the presence of HBr in H2O. Metalation of the bromo derivative (XL) with BuLi in THF at –78 °C, followed by quenching with CO2 affords the lithium carboxylate (II) , which is converted to the carboxylic acid (III) by treatment with HCl in EtOH. Alternatively, cyanation of bromide (XL) with NaCN/CuCN in DMAc at 150 °C yields nitrile (XLIII), which is hydrolyzed to carboxylate (II) using LiOH in EtOH . In one further method, deamination of intermediate (XXXVII) by diazotization with NaNO2 and H2SO4 in the presence of hypophosphorous acid in H2O gives 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine (XLIV) , which is carboxylated to compound (II) by metalation with BuLi in THF at –78 °C and subsequent quenching with CO2 , or by acylation with trichloroacetyl chloride and Et3N in toluene, followed by haloform reaction of the resultant trichloromethyl ketone in the presence of LiOH .
The tetrahydrothiazolopyridine intermediate (XLIV) can also be prepared by a different procedure. After protection of 4-aminopyridine (XLV) as the N-Boc derivative (XLVI) with Boc2O in THF, treatment with BuLi in cold THF, followed by elemental sulfur yields the 3-sulfanylpyridine (XLVI). Cyclization of the Boc-protected amino thiol (XLVI) with formic acid at reflux, followed by KOH in H2O or Et2O leads to thiazolo[5,4-c]pyridine (XLVII), which is converted to the target intermediate (XLIV) by quaternization with iodomethane in DMF at 80 °C and then reduction with NaBH4 in MeOH .
| 【1】 Nagasawa, Sato, K., Yagi, T., H., Kitani, Y. (Daiichi Sankyo Co., Ltd.).Process for producing thiazole derivative. CA 2545730, EP 1683800, US 7547786, US 2007135476, US 2009192313. |
| 【2】 Ohta, T., Komoyira, S., Yoshimo, T. et al. (Daiichi Sankyo Co., Ltd.).Diamine derivatives. CA 2451605, CA 2456841, EP 1405852, EP 1415992, JP 2008143905, US 2005020645, US 2005119486, US 2005245565, US 2008015215, US 2009270446, US 7342014, US 7365205, WO 2003000657, WO 2003000680, WO 2003016302. |
| 【3】 Ohta, T., Komoriya, S., Yoshino, T. et al. (Daiichi Sankyo Co., Ltd.). Diamine derivatives. CA 2511493, EP 1577301, JP 2007070369, JP 2008138011, US 2006252837, US 2009281074, US 7576135, WO 2004058715. |
| 【4】 Schwartz, H.M., Wu, W.-S., Marr, P.W., Jones, J.B. Predicting the enantiomeric selectivity of chymotrypsin. Homologous series of ester substances. J Am Chem Soc 1978, 100(16): 5199-203. |
| 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) | 69421 | lithium 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxylate | C8H9LiN2O2S | 详情 | 详情 | |
| (III) | 69422 | 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxylic acid hydrochloride | C8H10N2O2S.HCl | 详情 | 详情 | |
| (XVIII) | 69458 | tert-butyl (3-mercaptopyridin-4-yl)carbamate | C10H14N2O2S | 详情 | 详情 | |
| (XXXVI) | 18620 | tert-butyl 4-oxo-1-piperidinecarboxylate;BOC-Piperidone;N-(tert-Butoxycarbonyl)-4-piperidone; N-Boc-4-piperidone | 79099-07-3 | C10H17NO3 | 详情 | 详情 |
| (XXXVII) | 69450 | 2-amino-5-Boc-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine；tert-butyl 2-amino-6,7-dihydrothiazolo[5,4-c]pyridine-5(4H)-carboxylate；Thiazolo[5,4-c]pyridine-5(4H)-carboxylicacid, 2-amino-6,7-dihydro-, 1,1-dimethylethyl ester;2-Amino-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-5-carboxylicacid tert-butyl ester;2-Amino-6,7-dihydro-4H-thiazolo[5,4-c]pyridine-5-carboxylic acid tert-butylester | 365996-05-0 | C11H17N3O2S | 详情 | 详情 |
| (XXXVIII) | 69451 | tert-butyl 2-bromo-6,7-dihydrothiazolo[5,4-c]pyridine-5(4H)-carboxylate；Thiazolo[5,4-c]pyridine-5(4H)-carboxylicacid, 2-bromo-6,7-dihydro-, 1,1-dimethylethyl ester;2-Bromo-5-(tert-butoxycarbonyl)-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine；2-Bromo-6,7-dihydro-4H-thiazolo[5,4-c]pyridine-5-carboxylic acid tert-butylester;2-Bromo-6,7-dihydro[1,3]thiazolo[5,4-c]pyridine-5(4H)-carboxylic acidtert-butyl ester | 365996-06-1 | C11H15BrN2O2S | 详情 | 详情 |
| (XXXIX) | 69452 | 2-bromo-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine 2,2,2-trifluoroacetate | C8H8BrF3N2O2S | 详情 | 详情 | |
| (XL) | 69453 | 2-bromo-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine | C7H9BrN2S | 详情 | 详情 | |
| (XLI) | 10919 | 1-Methyl-4-piperidone; 1-Methyltetrahydro-4(1H)-pyridinone; N-Methyl-4-piperidone;1-methylpiperidin-4-one | 1445-73-4 | C6H11NO | 详情 | 详情 |
| (XLII) | 69454 | 2-amino-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine;5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-amine | C7H11N3S | 详情 | 详情 | |
| (XLIII) | 69455 | 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carbonitrile | C8H9N3S | 详情 | 详情 | |
| (XLIV) | 69456 | 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine | 259809-24-0 | C7H10N2S | 详情 | 详情 |
| (XLV) | 25661 | 4-pyridinamine; 4-aminopyridine | 5044-74-5 | C5H6N2 | 详情 | 详情 |
| (XLVI) | 69457 | tert-butyl pyridin-4-ylcarbamate;4-(Boc-amino)pyridine;4-(tert-Butoxycarbonylamino)pyridine | 98400-69-2 | C10H14N2O2 | 详情 | 详情 |
| (XLVII) | 69459 | 4,5,6,7-tetrahydro-thiazolo[5,4-c]pyridine | C6H8N2S | 详情 | 详情 |