Cesium carbonate → 2-(4-(1-methyl-1H-benzo[d]imidazol-2-ylamino)phenoxy)nicotinonitrile

HRID 410187

反応式

HRID 410187 の反応式
[CH3:1][N:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[N:4]=[C:3]1[NH:11][C:12]1[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=1.C(=O)([O-])[O-].[Cs+].[Cs+].F[C:26]1[N:33]=[CH:32][CH:31]=[CH:30][C:27]=1[C:28]#[N:29]>CS(C)=O.CCOC(C)=O>[CH3:1][N:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[N:4]=[C:3]1[NH:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][C:26]2[N:33]=[CH:32][CH:31]=[CH:30][C:27]=2[C:28]#[N:29])=[CH:14][CH:13]=1

参加物

6

反応物 3

HCID 10796Cesium carbonateHCID 27832543-Cyano-2-fluoropyridineHCID 593270144-(1-methyl-1H-benzoimidazol-2-ylamino)-phenol

生成物 1

HCID 593271972-(4-(1-methyl-1H-benzo[d]imidazol-2-ylamino)phenoxy)nicotinonitrile

試薬・触媒・溶媒 2

HCID 679Dimethyl Sulfoxide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
80 °C

実験手順

To a solution of 4-(1-methyl-1H-benzo[d]imidazol-2-ylamino)phenol (120 mg, 0.5 mmol) in DMSO (1 mL) was added cesium carbonate (196 mg, 0.6 mmol) and 2-fluoronicotinonitrile (61 mg, 0.5 mmol). The resulting mixture was heated to 80° C. for 16 h. After cooling to RT, the reaction mixture was diluted with EtOAc and washed with water and brine several times to remove DMSO. The aqueous layer was back extracted with EtOAc (3×) and the combined organic layer was dried (Na2SO4) and concentrated. The crude product was chromatographed through a Redi-Sep® pre-packed silica gel column (40 g), eluting with a gradient of 0% to 5% of MeOH in CH2Cl2, followed by trituration with ether, to provide 2-(4-(1-methyl-1H-benzo[d]imidazol-2-ylamino)phenoxy)nicotinonitrile as off-white solid. MS (ESI, pos. ion) m/z: 342.2 (M+1). IC50 (uM) +++++.

後処理

  1. temperatureAfter cooling to RT
  2. washwashed with water and brine several times
  3. customto remove DMSO
  4. extractionThe aqueous layer was back extracted with EtOAc (3×)
  5. dry with materialthe combined organic layer was dried (Na2SO4)
  6. concentrationconcentrated
  7. customThe crude product was chromatographed through a Redi-Sep® pre-packed silica gel column (40 g)
  8. washeluting with a gradient of 0% to 5% of MeOH in CH2Cl2

出典と根拠

ORDレコード
ord-39b4b9cfc4b44c0e8bd30f1e7835c411
出典データセット
uspto-grants-2014_06
特許番号
US08759532B2

関連ノート

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