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【结 构 式】 
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【分子编号】28416 【品名】4-Fluoro-alpha-(4-methylphenylsulfanyl)benzyl isocyanide 【CA登记号】 |
【 分 子 式 】C15H12FNS 【 分 子 量 】257.3314232 【元素组成】C 70.01% H 4.7% F 7.38% N 5.44% S 12.46% |
合成路线1
该中间体在本合成路线中的序号：(XII)The condensation of pyruvic aldehyde dimethyl acetal (I) with dimethylformamide dimethyl acetal (II) afforded ketoenamine (III), which was condensed with N-methyl guanidine (IV) to give pyrimidine (V). Acid hydrolysis of the acetal function of (V) yielded pyrimidine carboxaldehyde (VI), which was converted to the imine (VIII) by treatment with 1-Boc-4-aminopiperidine (VII). Isonitrile (XII) was prepared by condensation of 4-fluorobenzaldehyde (IX) with formamide and p-thiocresol (X), followed by dehydration of the resulting formamide (XI) by means of POCl3 and Et3N. Reaction of isonitrile (XII) with imine (VIII) in the presence of 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) produced imidazole (XIII). Finally, acid deprotection of the Boc group of (XIII) provided the title compound.
| 【1】 Adams, J.L.; Gallagher, T.F.; Garigipati, R.S.; Boehm, J.C.; Sisko, J.; Peng, Z.-Q.; Lee, J.C.-L. (SmithKline Beecham plc); Certain 1,4,5-tri-substd. imidazole cpds. useful as cytokine. EP 0809499; JP 1998512555; US 5593992; WO 9621452 . |
| 【2】 Garigipati, R.S.; Adams, J.L.; Boehm, J.C. (SmithKline Beecham Corp.); Pyridyl imidazole cpds. and compsns.. US 5670527 . |
| 【3】 Adams, J.L.; Boehm, J.C.; Imidazole cpds., use and process of making. US 5593991 . |
| 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) | 25433 | 1,1-dimethoxyacetone | 6342-56-9 | C5H10O3 | 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) | 25434 | (E)-4-(dimethylamino)-1,1-dimethoxy-3-buten-2-one | C8H15NO3 | 详情 | 详情 | |
| (IV) | 28411 | N-Methylguanidine | 598-12-9 | C2H7N3 | 详情 | 详情 |
| (V) | 28412 | 4-(dimethoxymethyl)-N-methyl-2-pyrimidinamine | C8H13N3O2 | 详情 | 详情 | |
| (VI) | 28413 | 2-(methylamino)-4-pyrimidinecarbaldehyde | C6H7N3O | 详情 | 详情 | |
| (VII) | 28414 | 4-Amino-1-N-Boc-piperidine; tert-butyl 4-amino-1-piperidinecarboxylate; N-Boc-4-aminopiperidine | 87120-72-7 | C10H20N2O2 | 详情 | 详情 |
| (VIII) | 28415 | tert-butyl 4-([(Z)-[2-(methylamino)-4-pyrimidinyl]methylidene]amino)-1-piperidinecarboxylate | C16H25N5O2 | 详情 | 详情 | |
| (IX) | 12337 | 4-fluorobenzaldehyde | 459-57-4 | C7H5FO | 详情 | 详情 |
| (X) | 25437 | 4-methylphenylhydrosulfide | 106-45-6 | C7H8S | 详情 | 详情 |
| (XI) | 25438 | (4-fluorophenyl)[(4-methylphenyl)sulfanyl]methylformamide | C15H14FNOS | 详情 | 详情 | |
| (XII) | 28416 | 4-Fluoro-alpha-(4-methylphenylsulfanyl)benzyl isocyanide | C15H12FNS | 详情 | 详情 | |
| (XIII) | 28417 | tert-butyl 4-[4-(4-fluorophenyl)-5-[2-(methylamino)-4-pyrimidinyl]-1H-imidazol-1-yl]-1-piperidinecarboxylate | C24H29FN6O2 | 详情 | 详情 |