Methanesulfonic anhydride → ethyl 4-((5-chloro-1-methyl-6-oxo-1,6-dihydropyridin-3-ylamino)(4-chloro-2-fluorophenyl)methyl)-1-(2,4-dimethoxypyrimidin-5-yl)-5-isopropyl-1H-pyrazole-3-carboxylate

HRID 869078ノート

反応式

HRID 869078 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8](O)[C:9]2[C:10]([C:27]([O:29][CH2:30][CH3:31])=[O:28])=[N:11][N:12]([C:17]3[C:18]([O:25][CH3:26])=[N:19][C:20]([O:23][CH3:24])=[N:21][CH:22]=3)[C:13]=2[CH:14]([CH3:16])[CH3:15])=[C:4]([F:33])[CH:3]=1.CS(OS(C)(=O)=O)(=O)=O.[NH2:43][C:44]1[CH:45]=[C:46]([Cl:52])[C:47](=[O:51])[N:48]([CH3:50])[CH:49]=1>C(Cl)Cl>[Cl:52][C:46]1[C:47](=[O:51])[N:48]([CH3:50])[CH:49]=[C:44]([NH:43][CH:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][C:4]=2[F:33])[C:9]2[C:10]([C:27]([O:29][CH2:30][CH3:31])=[O:28])=[N:11][N:12]([C:17]3[C:18]([O:25][CH3:26])=[N:19][C:20]([O:23][CH3:24])=[N:21][CH:22]=3)[C:13]=2[CH:14]([CH3:16])[CH3:15])[CH:45]=1

参加物

5

反応物 3

HCID 81560Methanesulfonic anhydrideHCID 717560735-Amino-3-chloro-1-methyl-1,2-dihydropyridin-2-oneHCID 89601495ethyl 4-((4-chloro-2-fluorophenyl)(hydroxy)methyl)-1-(2,4-dimethoxypyrimidin-5-yl)-5-isopropyl-1H-pyrazole-3-carboxylate

生成物 1

HCID 89602440ethyl 4-((5-chloro-1-methyl-6-oxo-1,6-dihydropyridin-3-ylamino)(4-chloro-2-fluorophenyl)methyl)-1-(2,4-dimethoxypyrimidin-5-yl)-5-isopropyl-1H-pyrazole-3-carboxylate収率 80.3%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

A solution of 485 mg (0.944 mmol) ethyl 4-((4-chloro-2-fluorophenyl)(hydroxy)methyl)-1-(2,4-dimethoxypyrimidin-5-yl)-5-isopropyl-1H-pyrazole-3-carboxylate (product from step 184.3), 0.658 ml (4.72 mmol) TEA in 19 ml CH2Cl2 was cooled down to 0° C. 411 mg (1.41 mmol) methanesulfonic anhydride was added and the solution was allowed to warm to RT. 229 mg (1.416 mmol) 5-amino-3-chloro-1-methylpyridin-2(1H)-one (intermediate W1) was added and the solution was stirred for 1.5 hour. The mixture was diluted with CH2Cl2 and washed with 1M NaHCO3 solution. The water phase was extracted with CH2Cl2. The combined organic phases were dried (Na2SO4), filtered and evaporated. The crude product was purified by column chromatography (Silicagel, heptane, EtOAc) to give 474 mg (0.758 mmol, 80% yield) of the title compound as a brown oil. LCMS: (M+H)=619/621; tR=1.13 min (LC-MS 4). HPLC: tR=5.52 min (HPLC 7). TLC: Rf=0.09 (Heptane/EtOAc 1:2).

後処理

  1. washwashed with 1M NaHCO3 solution
  2. extractionThe water phase was extracted with CH2Cl2
  3. dry with materialThe combined organic phases were dried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated
  6. customThe crude product was purified by column chromatography (Silicagel, heptane, EtOAc)

出典と根拠

ORDレコード
ord-aa5a1928384e4e149688c5a58c38351f
出典データセット
uspto-grants-2015_03
特許番号
US08969341B2

反応ノート

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