1,3-Dimethyl-2-imidazolidinone → N-[4-(4-Fluoro-2-methoxy-phenyl)-6-methyl-pyridazin-3-yl]-3-methanesulfonyl-N-methyl-5-trifluoromethyl-benzamide

HRID 403374ノート

反応式

HRID 403374 の反応式
Cl[C:2]1[N:7]=[N:6][C:5]([N:8]([CH3:25])[C:9](=[O:24])[C:10]2[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[C:12]([S:20]([CH3:23])(=[O:22])=[O:21])[CH:11]=2)=[C:4]([C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][C:27]=2[O:33][CH3:34])[CH:3]=1.[Cl-].C[Zn+].[CH3:38]N1CCN(C)C1=O.C(=O)(O)[O-].[Na+]>O1CCCC1.C(OCC)(=O)C>[F:32][C:29]1[CH:30]=[CH:31][C:26]([C:4]2[CH:3]=[C:2]([CH3:38])[N:7]=[N:6][C:5]=2[N:8]([CH3:25])[C:9](=[O:24])[C:10]2[CH:15]=[C:14]([C:16]([F:18])([F:17])[F:19])[CH:13]=[C:12]([S:20]([CH3:23])(=[O:21])=[O:22])[CH:11]=2)=[C:27]([O:33][CH3:34])[CH:28]=1

参加物

7

反応物 4

HCID 66611,3-Dimethyl-2-imidazolidinoneHCID 516892Sodium BicarbonateHCID 71766083HCID 71766083、化合物HCID 178477797HCID 178477797、化合物

生成物 1

HCID 71766084N-[4-(4-Fluoro-2-methoxy-phenyl)-6-methyl-pyridazin-3-yl]-3-methanesulfonyl-N-methyl-5-trifluoromethyl-benzamide

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
60 °C

実験手順

To a solution of N-[6-chloro-4-(4-fluoro-2-methoxy-phenyl)-pyridazin-3-yl]-3-methanesulfonyl-N-methyl-5-trifluoromethyl-benzamide (100 mg, 193 mmol, example 1) in tetrahydrofuran (2 mL) was added methylzinc chloride (2M solution in tetrahydrofuran, 145 μL, 290 mmol) and 1,3-dimethyl-2-imidazolidinone (400 μL, CAS RN 80-73-9) and PEPPSI-IPr (2.62 mg, 3.86 μmol, CAS RN 905459-27-0). The reaction mixture was stirred at 60° C. for 5 hours, poured on 10% aqueous sodium bicarbonate solution (30 mL) and ethyl acetate (30 mL) and the layers were separated. The aqueous layer was extracted a second time with ethyl acetate (30 mL). The organic layers were washed with brine (30 mL), dried over magnesium sulfate, filtered and concentrated under vacuum. The compound was purified by silica gel chromatography on a 20 g column using an MPLC (Flashmaster) system eluting with a gradient of n-heptane:ethyl acetate (100:0 to 0:100). Light brown solid (70 mg, 72.9%). MS (ESI+): m/z=498.110 ([M+H]+).

後処理

  1. customthe layers were separated
  2. extractionThe aqueous layer was extracted a second time with ethyl acetate (30 mL)
  3. washThe organic layers were washed with brine (30 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe compound was purified by silica gel chromatography on a 20 g column
  8. washeluting with a gradient of n-heptane:ethyl acetate (100:0 to 0:100)

出典と根拠

ORDレコード
ord-5da0f6f10d2f47c9acf258a59ff8efdd
出典データセット
uspto-grants-2014_06
特許番号
US08748434B2

反応ノート

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