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

HRID 410187

반응식

HRID 410187 반응식
[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

참가 물질

6

반응물 3

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

생성물 1

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

시약·촉매·용매 2

HCID 679Dimethyl Sulfoxide용매HCID 8857Ethyl Acetate용매

반응 조건

온도
80 °C

실험 절차

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) +++++.

후처리

  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

출처 및 근거

ORD 기록
ord-39b4b9cfc4b44c0e8bd30f1e7835c411
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08759532B2

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