|
【结 构 式】 
|
【分子编号】33531 【品名】propiophenone 【CA登记号】93-55-0 |
【 分 子 式 】C9H10O 【 分 子 量 】134.1778 【元素组成】C 80.56% H 7.51% O 11.92% |
合成路线1
该中间体在本合成路线中的序号：(II)By a Grignard reaction between 3-trifluoromethylphenylmagnesium bromide (I) and propiophenone (II) in ethyl ether.
| 【1】 Edit, T.; et al. (Gedeon Richter Ltd.); alpha-Substituted benzhydrol derivatives and a process for the preparation thereof. BE 0818801; DE 2438399; FR 2240725; GB 1478185; JP 50062959; US 4039589 . |
| 【2】 Castaner, J.; Hillier, H.; Flumecinol. Drugs Fut 1978, 3, 10, 742. |
合成路线2
该中间体在本合成路线中的序号：(IV)By reaction of alpha,m-(dichloropropiophenone (I) with tert-butylamine (B) in refluxing acetonitrile or by reaction of alpha-bromo-m-chloropropiophenone (VI) with tert-butylamine (B) in acetonitrile at room temperature. The starting product (I) can be obtained in two different ways: 1) The Grignard condensation of m-chlorobenzonitrile (II) with ethyl magnesium bromide (A) in refluxing ether gives m-chloropropiophenone (III), which is then treated with SO2Cl2 in tetrachloroethane. 2) The reaction of propiophenone (IV) with SO2Cl2 in tetrachloroethane gives alpha-chloropropiophenone (V), which is then chlorinated in the ring by means of SO2Cl2 and AlCl3 in tetrachloroethane. The starting product (VI) is obtained by bromination of m-chloropropiophenone (III) with Br2 in methylene chloride
| 【1】 Mehta, N.B.; Yeowell, D.A.; Intermediates for biologically active ketones. CA 977778 . |
| 【2】 Mehta, N.B.; Yeowell, D.A.; Amino-propiophenones et medicaments contenant ces substances. DE 2059618; DE 2064934; FR 2081326; US 3819706 . |
| 【3】 Hopkins, S.J.; Castaner, J.; Bupropion. Drugs Fut 1978, 3, 10, 723. |
| 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) | 17895 | 2-Amino-2-methylpropane; tert-butylamine; 2-methyl-2-propanamine | 75-64-9 | C4H11N | 详情 | 详情 |
| (A) | 24239 | bromo(ethyl)magnesium；ethylmagnesium bromide | 925-90-6 | C2H5BrMg | 详情 | 详情 |
| (I) | 33569 | 2-chloro-1-(3-chlorophenyl)-1-propanone | C9H8Cl2O | 详情 | 详情 | |
| (II) | 33570 | 3-chlorobenzonitrile | 766-84-7 | C7H4ClN | 详情 | 详情 |
| (III) | 33571 | 3'-chloropropiophenone; 1-(3-chlorophenyl)-1-propanone | 34841-35-5 | C9H9ClO | 详情 | 详情 |
| (IV) | 33531 | propiophenone | 93-55-0 | C9H10O | 详情 | 详情 |
| (V) | 33572 | 2-chloro-1-phenyl-1-propanone | C9H9ClO | 详情 | 详情 | |
| (VI) | 33573 | 2-bromo-1-(3-chlorophenyl)-1-propanone | C9H8BrClO | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(IX)Propiophenone (IX) was condensed with diethyl oxalate to give diketone (X). Reaction with hydrazine (III) afforded pyrazole (XI). Nitration of (XI) by nitronium tetrafluoborate in acetonitrile gave a mixture of para- and ortho-nitrated compounds (XIIa-b), which were used without separation. Ester hydrolysis, followed by chlorination to (XIIIa-b) and condensation with 1-aminopiperidine (VI) gave the corresponding mixture of para- and ortho-nitro amides, which were separated by flash chromatography. The required para-isomer (XIV) was reduced by hydrazine and Raney Nickel to aniline (XV). This was finally converted to the title iodide via the reaction of the diazonium salt with NaI.
| 【1】 Fan, P.; Liu, Q.; Lan, R.; et al.; Structure-activity relationships of pyrazole derivatives as cannabinoid receptor antagonists. J Med Chem 1999, 42, 4, 769. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIIa) | 35786 | ethyl 1-(2,4-dichlorophenyl)-4-methyl-5-(2-nitrophenyl)-1H-pyrazole-3-carboxylate | C19H15Cl2N3O4 | 详情 | 详情 | |
| (XIIb) | 35787 | ethyl 1-(2,4-dichlorophenyl)-4-methyl-5-(4-nitrophenyl)-1H-pyrazole-3-carboxylate | C19H15Cl2N3O4 | 详情 | 详情 | |
| (XIIIa) | 35788 | 1-(2,4-dichlorophenyl)-4-methyl-5-(2-nitrophenyl)-1H-pyrazole-3-carbonyl chloride | C17H10Cl3N3O3 | 详情 | 详情 | |
| (XIIIb) | 35789 | 1-(2,4-dichlorophenyl)-4-methyl-5-(4-nitrophenyl)-1H-pyrazole-3-carbonyl chloride | C17H10Cl3N3O3 | 详情 | 详情 | |
| (III) | 35778 | 1-(2,4-dichlorophenyl)hydrazine | 5446-18-4 | C6H6Cl2N2 | 详情 | 详情 |
| (VI) | 35781 | 1-piperidinylamine; 1-piperidinamine | 2213-43-6 | C5H12N2 | 详情 | 详情 |
| (IX) | 33531 | propiophenone | 93-55-0 | C9H10O | 详情 | 详情 |
| (X) | 35784 | C13H13LiO4 | 详情 | 详情 | ||
| (XI) | 35785 | ethyl 1-(2,4-dichlorophenyl)-4-methyl-5-phenyl-1H-pyrazole-3-carboxylate | C19H16Cl2N2O2 | 详情 | 详情 | |
| (XIV) | 35790 | 1-(2,4-dichlorophenyl)-4-methyl-5-(4-nitrophenyl)-N-(1-piperidinyl)-1H-pyrazole-3-carboxamide | C22H21Cl2N5O3 | 详情 | 详情 | |
| (XV) | 35791 | 5-(4-aminophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(1-piperidinyl)-1H-pyrazole-3-carboxamide | C22H23Cl2N5O | 详情 | 详情 |