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

HRID 64461

반응식

HRID 64461 반응식
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]

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 11186Zinc cyanide (Zn(CN)2)촉매2회HCID 178477754HCID 178477754, 화합물촉매

반응 조건

온도
180 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-d606294be9834a4594300d4bcd62aef9
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09447090B2

연결된 노트

불러오는 중…