Sodium hydride → 3-Chloro-N-[4-(4-fluoro-2-methoxy-phenyl)-pyridin-3-yl]-5-methanesulfonyl-N-methyl-benzamide

HRID 878294

反応式

HRID 878294 の反応式
N1CCC[C@H]1C(O)=O.[H-].[Na+].[F:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:23]=[CH:22][N:21]=[CH:20][C:19]=2[N:24]([CH3:38])[C:25](=[O:37])[C:26]2[CH:31]=[C:30]([S:32]([CH3:35])(=[O:34])=[O:33])[CH:29]=[C:28](I)[CH:27]=2)=[C:14]([O:39][CH3:40])[CH:13]=1.CS([O-])(=O)=O.[Na+].[NH4+].[Cl-:48]>CS(C)=O.[Cu]I.CCOC(C)=O>[Cl:48][C:28]1[CH:27]=[C:26]([CH:31]=[C:30]([S:32]([CH3:35])(=[O:34])=[O:33])[CH:29]=1)[C:25]([N:24]([C:19]1[CH:20]=[N:21][CH:22]=[CH:23][C:18]=1[C:15]1[CH:16]=[CH:17][C:12]([F:11])=[CH:13][C:14]=1[O:39][CH3:40])[CH3:38])=[O:37]

参加物

9

反応物 5

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 145742L-ProlineHCID 638112Sodium methanesulfonateHCID 70663452N-[4-(4-fluoro-2-methoxy-phenyl)-pyridin-3-yl]-3-iodo-5-methanesulfonyl-N-methyl-benzamide

生成物 1

HCID 601969973-Chloro-N-[4-(4-fluoro-2-methoxy-phenyl)-pyridin-3-yl]-5-methanesulfonyl-N-methyl-benzamide

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 679Dimethyl Sulfoxide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of L-proline (27.8 mg, 242 μmol) in DMSO (3 ml) was added sodium hydride (9.66 mg, 242 μmol, 60% dispersion in mineral oil). The mixture was stirred at room temperature for 30 minutes then copper(I)iodide (46.0 mg, 242 μmol) and N-[4-(4-fluoro-2-methoxy-phenyl)-pyridin-3-yl]-3-iodo-5-methanesulfonyl-N-methyl-benzamide (150 mg, 302 μmol) and sodium methanesulfonate (247 mg, 2.42 mmol) were added. The reaction mixture was stirred for 4 hours at 120° C. The reaction mixture was poured on 30 mL 10% aqueous NH4Cl solution and 30 mL EtOAc and the layers were separated. The aqueous layer was extracted a second time with 30 mL EtOAc. The organic layers were washed with 30 mL brine, dried over MgSO4, filtered and concentrated under vacuum. The residue was purified by silica gel chromatography on a 20 g column using an MPLC (Flashmaster) system eluting with a gradient of n-heptane:EtOAc (100:0 to 0:100). Light yellow solid (121 mg, 89.3%). MS (ESI): m/z=449.071 [M+H]+.

後処理

  1. stirringThe reaction mixture was stirred for 4 hours at 120° C
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted a second time with 30 mL EtOAc
  4. washThe organic layers were washed with 30 mL brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe residue was purified by silica gel chromatography on a 20 g column
  9. washeluting with a gradient of n-heptane:EtOAc (100:0 to 0:100)

出典と根拠

ORDレコード
ord-112823149ffa45968b5d6ea8863ba856
出典データセット
uspto-grants-2015_03
特許番号
US08987307B2

関連ノート

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