|
【结 构 式】 
|
【分子编号】13624 【品名】1-Chloro-2-methylpropane; Isobutyl chloride 【CA登记号】513-36-0 |
【 分 子 式 】C4H9Cl 【 分 子 量 】92.56816 【元素组成】C 51.9% H 9.8% Cl 38.3% |
合成路线1
该中间体在本合成路线中的序号：(II)By reaction of theophylline sodium salt with isobutyl halogenide in N,N-dimethylformamide at 80 C.
| 【1】 Fedi, M.; Bonacchi, G. (Malesci Ist. Farmacobiol. SpA); Xanthine derivs., pharmaceutical compsns. containing same and their therapeutic use. US 4544556 . |
| 【2】 Bonacchi, G.; Manzini, S.; Dapporto, P.; Paoli, P.; Crystal structure of a new antibronchospastic drug: 1,3-dimethyl-7-isobutylxanthine (TE 06). In: Three-Dimensional Molecular Structure and Drug Action - 15th Course of International School of Crystallography (June 1-11, Erice) 1989, Poster No. 8. |
| 【3】 Manzini, S.; Fedi, M.; Bonacchi, G.; Agostini, O.; ISBUFYLLINE. Drugs Fut 1990, 15, 3, 228. |
合成路线2
该中间体在本合成路线中的序号：(IV)When 4-phenyl-3-oxobutanoic acid methyl ester (I) were reacted with thiourea (II), in the presence of sodium methoxide, condensation occurred with formation of 3,4-dihydro-6-benzyl-4-oxo-2-thioxopyrimidine (III). Reaction of the compound (III) with isobutyl chloride (IV) in alkaline medium afforded the required 2-(isobutylthio)-6-benzyl-3,4-dihydro-4-oxopyrimidine
| 【1】 Artico, M.; Selected non-nucleoside reverse transcriptase inhibitors (NNRTIs): the DABOs family. Drugs Fut 2002, 27, 2, 159. |
合成路线3
该中间体在本合成路线中的序号：(IV)When 4-(3-methylphenyl-3-oxobutanoic acid methyl ester (I) were reacted with thiourea (II), in the presence of sodium methoxide, condensation occurred with formation of 3,4-dihydro-6-(3-methylbenzyl)-4-oxo-2-thioxopyrimidine (III). Reaction of the compound (III) with isobutyl chloride (IV) in alkaline medium afforded the required 2-(isobutylthio)-6-(3-methylbenzyl)-3,4-dihydro-4-oxopyrimidine
| 【1】 Artico, M.; Selected non-nucleoside reverse transcriptase inhibitors (NNRTIs): the DABOs family. Drugs Fut 2002, 27, 2, 159. |
| 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) | 51787 | methyl (Z)-3-hydroxy-4-(3-methylphenyl)-2-butenoate | C12H14O3 | 详情 | 详情 | |
| (II) | 10180 | Thiourea | 62-56-6 | CH4N2S | 详情 | 详情 |
| (III) | 51801 | 6-(3-methylbenzyl)-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone | C12H12N2OS | 详情 | 详情 | |
| (IV) | 13624 | 1-Chloro-2-methylpropane; Isobutyl chloride | 513-36-0 | C4H9Cl | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(IV)When 2-methyl-4-phenyl-3-oxobutanoic acid methyl ester (I) were reacted with thiourea (II), in the presence of sodium methoxide, condensation occurred with formation of 5-methyl-3,4-dihydro-6-benzyl-4-oxo-2-thioxopyrimidine (III). Reaction of compound (III) with isobutyl chloride (IV) in alkaline medium afforded the required 2-(isobutylthio)-5-methyl-6-benzyl-3,4-dihydro-4-oxopyrimidine
| 【1】 Artico, M.; Selected non-nucleoside reverse transcriptase inhibitors (NNRTIs): the DABOs family. Drugs Fut 2002, 27, 2, 159. |
| 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) | 51789 | methyl (Z)-3-hydroxy-2-methyl-4-phenyl-2-butenoate | C12H14O3 | 详情 | 详情 | |
| (II) | 10180 | Thiourea | 62-56-6 | CH4N2S | 详情 | 详情 |
| (III) | 51800 | 6-benzyl-5-methyl-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone | C12H12N2OS | 详情 | 详情 | |
| (IV) | 13624 | 1-Chloro-2-methylpropane; Isobutyl chloride | 513-36-0 | C4H9Cl | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(IV)When 2-methyl-4-(3-methylphenyl)-3-oxobutanoic acid methyl ester (I) were reacted with thiourea (II), in the presence of sodium methoxide, condensation occurred with formation of 5-methyl-3,4-dihydro-6-(3-methylbenzyl)-4-oxo-2-thioxopyrimidine (III). Reaction of compound (III) with isobutyl chloride (IV) in alkaline medium afforded the required 2-(isobutylthio)-5-methyl-6-(3-methylbenzyl)-3,4-dihydro-4-oxopyrimidine
| 【1】 Artico, M.; Selected non-nucleoside reverse transcriptase inhibitors (NNRTIs): the DABOs family. Drugs Fut 2002, 27, 2, 159. |
| 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) | 51785 | methyl (Z)-3-hydroxy-2-methyl-4-(3-methylphenyl)-2-butenoate | C13H16O3 | 详情 | 详情 | |
| (II) | 10180 | Thiourea | 62-56-6 | CH4N2S | 详情 | 详情 |
| (III) | 51799 | 5-methyl-6-(3-methylbenzyl)-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone | C13H14N2OS | 详情 | 详情 | |
| (IV) | 13624 | 1-Chloro-2-methylpropane; Isobutyl chloride | 513-36-0 | C4H9Cl | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(VI)The condensation of 2-(2,6-difluorophenyl)acetic acid (I) with malonic acid monoethyl ester sodium salt (II) gives 4-(2,6-difluorophenyl)-3-oxobutyric acid ethyl ester (III), which is cyclized with thiourea (IV) to yield 6-(2,6-difluorobenzyl)-2-thioxo-1,2,3,4-tetrahydropyrimidin-4-one (V). Finally this compound is reacted with isobutyl chloride (VI) by means of K2CO3 to afford the target pyrimidinone.
| 【1】 Artico, M.; Selected non-nucleoside reverse transcriptase inhibitors (NNRTIs): the DABOs family. Drugs Fut 2002, 27, 2, 159. |
| 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) | 51809 | 2,6-Difluorophenylacetic acid | 85068-28-6 | C8H6F2O2 | 详情 | 详情 |
| (II) | 14338 | potassium 3-ethoxy-3-oxopropanoate | 6148-64-7 | C5H7KO4 | 详情 | 详情 |
| (III) | 51810 | ethyl 4-(2,6-difluorophenyl)-3-oxobutanoate | C12H12F2O3 | 详情 | 详情 | |
| (IV) | 10180 | Thiourea | 62-56-6 | CH4N2S | 详情 | 详情 |
| (V) | 51811 | 6-(2,6-difluorobenzyl)-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone | C11H8F2N2OS | 详情 | 详情 | |
| (VI) | 13624 | 1-Chloro-2-methylpropane; Isobutyl chloride | 513-36-0 | C4H9Cl | 详情 | 详情 |
合成路线7
该中间体在本合成路线中的序号：(VI)The condensation of 2-(2,6-difluorophenyl)acetic acid (I) with 2-methylmalonic acid monoethyl ester sodium salt (II) gives 4-(2,6-difluorophenyl)-2-methyl-3-oxobutyric acid ethyl ester (III), which is cyclized with thiourea (IV) to yield 6-(2,6-difluorobenzyl)-5-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-4-one (V). Finally this compound is reacted with isobutyl chloride (VI) by means of K2CO3 to afford the target pyrimidinone.
| 【1】 Artico, M.; Selected non-nucleoside reverse transcriptase inhibitors (NNRTIs): the DABOs family. Drugs Fut 2002, 27, 2, 159. |
| 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) | 51809 | 2,6-Difluorophenylacetic acid | 85068-28-6 | C8H6F2O2 | 详情 | 详情 |
| (II) | 51813 | potassium 3-ethoxy-2-methyl-3-oxopropanoate | C6H9KO4 | 详情 | 详情 | |
| (III) | 51814 | ethyl 4-(2,6-difluorophenyl)-2-methyl-3-oxobutanoate | C13H14F2O3 | 详情 | 详情 | |
| (IV) | 10180 | Thiourea | 62-56-6 | CH4N2S | 详情 | 详情 |
| (V) | 51815 | 6-(2,6-difluorobenzyl)-5-methyl-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone | C12H10F2N2OS | 详情 | 详情 | |
| (VI) | 13624 | 1-Chloro-2-methylpropane; Isobutyl chloride | 513-36-0 | C4H9Cl | 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 alkylation of 6-(2,6-difluorobenzyl)-5-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-4-one (I) with isobutyl chloride (II) by means of K2CO3 gives 6-(2,6-difluorobenzyl)-2-(isobutylsulfanyl)-5-methylpyridmidin-4(3H)-one (III), which is then methylated with Me-Cl and LDA in THF/HMPA to yield the target alpha-methylbenzyl pyrimidinone.
| 【1】 Artico, M.; Selected non-nucleoside reverse transcriptase inhibitors (NNRTIs): the DABOs family. Drugs Fut 2002, 27, 2, 159. |
| 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) | 51815 | 6-(2,6-difluorobenzyl)-5-methyl-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone | C12H10F2N2OS | 详情 | 详情 | |
| (II) | 13624 | 1-Chloro-2-methylpropane; Isobutyl chloride | 513-36-0 | C4H9Cl | 详情 | 详情 |
| (III) | 51823 | 6-(2,6-difluorobenzyl)-2-(isobutylsulfanyl)-5-methyl-4(3H)-pyrimidinone | C16H18F2N2OS | 详情 | 详情 |