Ethyl Acetate → 6-cyano-8-(cyclohexylmethoxy)-N-[(1R)-2-hydroxy-1-phenylethyl]-2-methylimidazo[1,2-a]pyridine-3-carboxamide

HRID 64461

反応式

HRID 64461 の反応式
Br[C:2]1[CH:3]=[C:4]([O:24][CH2:25][CH:26]2[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]2)[C:5]2[N:6]([C:8]([C:12]([NH:14][C@H:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH2:16][OH:17])=[O:13])=[C:9]([CH3:11])[N:10]=2)[CH:7]=1.C(OCC)(=O)C.[CH3:38][N:39]1CCCC1=O>[C-]#N.[Zn+2].[C-]#N.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Fe]>[C:38]([C:2]1[CH:3]=[C:4]([O:24][CH2:25][CH:26]2[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]2)[C:5]2[N:6]([C:8]([C:12]([NH:14][C@H:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH2:16][OH:17])=[O:13])=[C:9]([CH3:11])[N:10]=2)[CH:7]=1)#[N:39]

参加物

6

反応物 3

HCID 8857Ethyl AcetateHCID 13387N-methyl-2-pyrrolidoneHCID 867134786-bromo-8-(cyclohexylmethoxy)-N-[(1R)-2-hydroxy-1-phenylethyl]-2-methylimidazo[1,2-a]pyridine-3-carboxamide

生成物 1

HCID 867134776-cyano-8-(cyclohexylmethoxy)-N-[(1R)-2-hydroxy-1-phenylethyl]-2-methylimidazo[1,2-a]pyridine-3-carboxamide

試薬・触媒・溶媒 2

HCID 11186Zinc cyanide (Zn(CN)2)触媒2 回HCID 178477754HCID 178477754、化合物触媒

反応条件

温度
180 °C

実験手順

To a solution of 90 mg of 6-bromo-8-(cyclohexylmethoxy)-N-[(1R)-2-hydroxy-1-phenylethyl]-2-methylimidazo[1,2-a]pyridine-3-carboxamide in 1.8 ml of N-methyl-2-pyrrolidone were added 54 mg of zinc cyanide and 27 mg of [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium (II), followed by stirring at 180° C. for 30 minutes under a condition for microwave irradiation. To the reaction mixture was added 46 mg of zinc cyanide, followed by further stirring at 180° C. for 30 minutes under a condition for microwave irradiation. To the reaction mixture were added ethyl acetate and a saturated aqueous sodium hydrogen carbonate solution, followed by filtration through Celite. A layer separation operation of the obtained filtrate was carried out, the organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 7 mg of 6-cyano-8-(cyclohexylmethoxy)-N-[(1R)-2-hydroxy-1-phenylethyl]-2-methylimidazo[1,2-a]pyridine-3-carboxamide.

後処理

  1. stirringby further stirring at 180° C. for 30 minutes under a condition for microwave irradiation
  2. filtrationa saturated aqueous sodium hydrogen carbonate solution, followed by filtration through Celite
  3. customA layer separation operation of the obtained filtrate
  4. washthe organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography

出典と根拠

ORDレコード
ord-d606294be9834a4594300d4bcd62aef9
出典データセット
uspto-grants-2016_09
特許番号
US09447090B2

関連ノート

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