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【结 构 式】 
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【分子编号】47518 【品名】2-Amino-4-nitrotoluene; 5-Nitro-o-toluidine; 4-Nitro-2-aminotoluene; 2-methyl-5-nitrophenylamine; 2-methyl-5-nitroaniline 【CA登记号】99-55-8 |
【 分 子 式 】C7H8N2O2 【 分 子 量 】152.1528 【元素组成】C 55.26% H 5.3% N 18.41% O 21.03% |
与该中间体有关的原料药合成路线共 3 条
合成路线1
该中间体在本合成路线中的序号：(V)The condensation of 1-(3-pyridyl)ethanone (I) with dimethylformamide dimethylacetal (II) gives 3-(dimethylamino)-1-(3-pyridyl)-2-propen-1-one (III), which is cyclized with 1-(2-methyl-5-nitrophenyl)guanidine (IV) [obtained by reaction of 2-methyl-5-nitroaniline (V) with cyanamide (VI)] in refluxing isopropanol to yield the pyrimidine derivative (VII). Reduction of the nitro group of (VII) with H2 over Pd/C in THF affords the corresponding amino compound (VIII), which is finally condensed with 4-(4-methylpiperazin-1-ylmethyl)benzoyl chloride (IV) in pyridine.
| 【1】 Castaner, J.; Fernandez, R.; de Bree, F.; Sorbera, L.A.; Imatinib Mesilate. Drugs Fut 2001, 26, 6, 545. |
| 【2】 Buchdunger, E.; Mett, H.; Meyer, T.; Lydon, N.B.; Zimmermann, J.; Potent and selective inhibitors of the Abl-kinase: Phenylaminopyrimidine (PAP) derivatives. Bioorg Med Chem Lett 1997, 7, 2, 187. |
| 【3】 Zimmermann, J. (Novartis AG); Pyrimidine derivs. and process for their preparation. EP 0564409; JP 1994087834; US 5521184 . |
| 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) | 12027 | 1-(3-Pyridinyl)-1-ethanone; 1-(3-Pyridinyl)ethanone | 350-03-8 | C7H7NO | 详情 | 详情 |
| (II) | 11984 | N-(Dimethoxymethyl)-N,N-dimethylamine;dimethylformamide dimethylacetal;1,1-dimethoxy-N,N-dimethylmethanamine； Dimethoxy-N,N-dimethylmethanamine; N,N-Dimethylformamide dimethyl acetal | 4637-24-5 | C5H13NO2 | 详情 | 详情 |
| (III) | 47516 | (E)-3-(dimethylamino)-1-(3-pyridinyl)-2-propen-1-one | 123367-26-0 | C10H12N2O | 详情 | 详情 |
| (IV) | 47517 | N-(2-methyl-5-nitrophenyl)guanidine | 152460-07-6 | C8H10N4O2 | 详情 | 详情 |
| (V) | 47518 | 2-Amino-4-nitrotoluene; 5-Nitro-o-toluidine; 4-Nitro-2-aminotoluene; 2-methyl-5-nitrophenylamine; 2-methyl-5-nitroaniline | 99-55-8 | C7H8N2O2 | 详情 | 详情 |
| (VI) | 19648 | Cyanamide | 420-04-2 | CH2N2 | 详情 | 详情 |
| (VII) | 47519 | N-(2-methyl-5-nitrophenyl)-N-[4-(3-pyridinyl)-2-pyrimidinyl]amine; N-(2-methyl-5-nitrophenyl)-4-(3-pyridinyl)-2-pyrimidinamine | 152460-09-8 | C16H13N5O2 | 详情 | 详情 |
| (VIII) | 47520 | 4-methyl-N(3)-[4-(3-pyridinyl)-2-pyrimidinyl]-1,3-benzenediamine; N-(5-amino-2-methylphenyl)-N-[4-(3-pyridinyl)-2-pyrimidinyl]amine | 152460-10-1 | C16H15N5 | 详情 | 详情 |
| (IX) | 47521 | 4-[(4-methyl-1-piperazinyl)methyl]benzoyl chloride | 148077-69-4 | C13H17ClN2O | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)
| 【1】 Kompella A, Bhujanga Rao AKS, Venkaiah Chowdary N, et aL 2004. Process for the preparation of the anti-cancer drug imatinib and its analogs via aminolysis of a (chloromethyl benzamide intermediate. WO 2004108699(本专利申请人为: Natco Pharma Limited, India) |
| 【2】 Szczepek W, Luniewski W, Kaczmarek L, et aL 2006.A process for preparation of imatinib base. W0 2006071130(本专利申请人为: Instytut Farmaceutyczny, Pol) |
| 【3】 Szakacs Z,Beni S,VargaZ,et aL 2005. Acid-base profiling of imatinib(gleevec) and its fragments. J Med Chem,8(1): 249一255 |
| 【4】 Zimmermann J.Buchdunger E, Mett H, et aL 1997. Potent and selective inhibitors of the abl-kinase: phenylaminopyrimidine (PAP) derivatives. Bioorg Med Chem Lett,7(2): 187～191 |
| 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) | 47518 | 2-Amino-4-nitrotoluene; 5-Nitro-o-toluidine; 4-Nitro-2-aminotoluene; 2-methyl-5-nitrophenylamine; 2-methyl-5-nitroaniline | 99-55-8 | C7H8N2O2 | 详情 | 详情 |
| (II) | 47517 | N-(2-methyl-5-nitrophenyl)guanidine | 152460-07-6 | C8H10N4O2 | 详情 | 详情 |
| (III) | 47516 | (E)-3-(dimethylamino)-1-(3-pyridinyl)-2-propen-1-one | 123367-26-0 | C10H12N2O | 详情 | 详情 |
| (IV) | 47519 | N-(2-methyl-5-nitrophenyl)-N-[4-(3-pyridinyl)-2-pyrimidinyl]amine; N-(2-methyl-5-nitrophenyl)-4-(3-pyridinyl)-2-pyrimidinamine | 152460-09-8 | C16H13N5O2 | 详情 | 详情 |
| (V) | 47520 | 4-methyl-N(3)-[4-(3-pyridinyl)-2-pyrimidinyl]-1,3-benzenediamine; N-(5-amino-2-methylphenyl)-N-[4-(3-pyridinyl)-2-pyrimidinyl]amine | 152460-10-1 | C16H15N5 | 详情 | 详情 |
| (VI) | 49112 | 4-(Chloromethyl)benzoyl chloride; p-(Chloromethyl)benzoyl chloride | 876-08-4 | C8H6Cl2O | 详情 | 详情 |
| (VII) | 66476 | 4-(chloromethyl)-N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)benzamide | 404844-11-7 | C24H20ClN5O | 详情 | 详情 |
| (VIII) | 10061 | 1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine | 109-01-3 | C5H12N2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(I)
| 【1】 Huang AL,Xing L.Zelikovitch L,et al.2006.Multi-step process for preparing imatinib. US 2006149061. |
| 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) | 47518 | 2-Amino-4-nitrotoluene; 5-Nitro-o-toluidine; 4-Nitro-2-aminotoluene; 2-methyl-5-nitrophenylamine; 2-methyl-5-nitroaniline | 99-55-8 | C7H8N2O2 | 详情 | 详情 |
| (II) | 66477 | 4-(3-Pyridyl)-2-chloropyrimidine;2-Chloro-4-(3-pyridyl)pyrimidine;2-Chloro-4-(pyridin-3-yl)pyrimidine | 483324-01-2 | C9H6ClN3 | 详情 | 详情 |
| (III) | 47519 | N-(2-methyl-5-nitrophenyl)-N-[4-(3-pyridinyl)-2-pyrimidinyl]amine; N-(2-methyl-5-nitrophenyl)-4-(3-pyridinyl)-2-pyrimidinamine | 152460-09-8 | C16H13N5O2 | 详情 | 详情 |
| (IV) | 47520 | 4-methyl-N(3)-[4-(3-pyridinyl)-2-pyrimidinyl]-1,3-benzenediamine; N-(5-amino-2-methylphenyl)-N-[4-(3-pyridinyl)-2-pyrimidinyl]amine | 152460-10-1 | C16H15N5 | 详情 | 详情 |
| (V) | 47521 | 4-[(4-methyl-1-piperazinyl)methyl]benzoyl chloride | 148077-69-4 | C13H17ClN2O | 详情 | 详情 |
Extended Information