Cesium carbonate → Ethyl 8-[(3,5-difluoropyridine-4-yl)methoxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylate

HRID 1844185ノート

反応式

HRID 1844185 の反応式
Cl[CH2:2][C:3]1[C:8]([F:9])=[CH:7][N:6]=[CH:5][C:4]=1[F:10].C(=O)([O-])[O-].[Cs+].[Cs+].[OH:17][C:18]1[C:19]2[N:20]([C:24]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[C:25]([CH3:27])[N:26]=2)[CH:21]=[CH:22][CH:23]=1>CN(C=O)C.O>[F:10][C:4]1[CH:5]=[N:6][CH:7]=[C:8]([F:9])[C:3]=1[CH2:2][O:17][C:18]1[C:19]2[N:20]([C:24]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[C:25]([CH3:27])[N:26]=2)[CH:21]=[CH:22][CH:23]=1

参加物

6

反応物 3

HCID 10796Cesium carbonateHCID 21717316Ethyl 8-hydroxy-2-methylimidazo[1,2-a]pyridine-3-carboxylateHCID 867182084-(Chloromethyl)-3,5-difluoropyridine

生成物 1

HCID 86718212Ethyl 8-[(3,5-difluoropyridine-4-yl)methoxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylate

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
60 °C

実験手順

At RT, 1.86 g of 4-(chloromethyl)-3,5-difluoropyridine (Example 115A, 9.1 mmol, 2.0 equivalent) and 4.44 g of caesium carbonate (13.6 mmol, 3 equivalent) were added to 1.0 g of ethyl 8-hydroxy-2-methylimidazo[1,2-a]pyridine-3-carboxylate (Example 3A, 4.54 mmol, 1.0 equivalent) in 100 ml of DMF, and the mixture was stirred at 60° C. for 1 h. The mixture was then diluted with 500 ml of water and extracted twice with in each case 300 ml of ethyl acetate. The combined organic phases were washed with 400 ml of saturated aqueous sodium chloride solution, dried over sodium sulphate and concentrated using a rotary evaporator. The residue obtained was purified on a silica gel column (mobile phase: cyclohexane/ethyl acetate 7:1 to 1:1). This gave 900 mg (54% of theory) and 200 mg (13% of theory; purity about 85%) of the title compound.

後処理

  1. extractionextracted twice with in each case 300 ml of ethyl acetate
  2. washThe combined organic phases were washed with 400 ml of saturated aqueous sodium chloride solution
  3. dry with materialdried over sodium sulphate
  4. concentrationconcentrated
  5. customa rotary evaporator
  6. customThe residue obtained
  7. customwas purified on a silica gel column (mobile phase: cyclohexane/ethyl acetate 7:1 to 1:1)

出典と根拠

ORDレコード
ord-01ae87594b5c40dcb2b0eac28b45d450
出典データセット
uspto-grants-2015_02
特許番号
US08946215B2

反応ノート

読み込み中…