Hydrochloric Acid → N-(1-(2,4-difluorophenyl)-1H-pyrazol-5-yl)acetamide

HRID 383566

반응식

HRID 383566 반응식
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:13]([NH2:14])=[CH:12][CH:11]=[N:10]1.[CH3:15][C:16](OC(C)=O)=[O:17].CCN(CC)CC.[OH-].[K+].Cl>ClCCCl.CN(C1C=CN=CC=1)C.C(Cl)Cl.CCO.CC(O)=O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:13]([NH:14][C:16](=[O:17])[CH3:15])=[CH:12][CH:11]=[N:10]1

참가 물질

11

반응물 5

HCID 313Hydrochloric AcidHCID 7918Acetic Anhydride2회HCID 8471TriethylamineHCID 14797Potassium HydroxideHCID 433167681-(2,4-Difluorophenyl)-1H-pyrazol-5-amine

생성물 1

HCID 67199804N-(1-(2,4-difluorophenyl)-1H-pyrazol-5-yl)acetamide

시약·촉매·용매 5

HCID 142844-(Dimethylamino)pyridine촉매HCID 111,2-Dichloroethane용매HCID 176Acetic Acid용매HCID 702Ethanol용매HCID 6344Dichloromethane용매

반응 조건

온도
80 °C

실험 절차

A solution of 1-(2,4-difluorophenyl)-1H-pyrazol-5-amine (5.00 g, 26 mmol), in 80 mL of 1,2-DCE was added DMAP (0.94 g, 7.7 mmol), Ac2O (12 mL, 128 mmol) and Et3N (18 mL, 128 mmol). The dark brown reaction mixture was heated at 80° C. in an oil bath for 18 h. After cooling to RT, it was diluted with 20 mL of DCM and washed with saturated aqueous solution of sodium bicarbonate, and brine. The resulting organic solution was then dried over magnesium sulfate and concentrated under reduced pressure to give viscous brown oil which contains the bis-acylated product along with residual amount of Ac2O and AcOH. The viscous brown oil was dissolved in 50 mL of EtOH and treated with KOH (5.0 g 129 mmol). After the reaction mixture was stirred at RT for 4 h, it was acidified with 2 N HCl to pH 4. The volatile portion was removed on the rotovap. The residue was diluted with 150 mL of EtOAc, washed with saturated aqueous solution of sodium bicarbonate, and brine. The resulting organic solution was then dried over magnesium sulfate and concentrated under reduced pressure. Purification of the crude material on an ISCO 80 g column (60-100% EtOAc in hexanes) afforded N-(1-(2,4-difluorophenyl)-1H-pyrazol-5-yl)acetamide as an off-white solid. MS (ES+): 238.1 (M+H)+.

후처리

  1. temperatureAfter cooling to RT
  2. washwashed with saturated aqueous solution of sodium bicarbonate, and brine
  3. dry with materialThe resulting organic solution was then dried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customto give viscous brown oil which
  6. customThe volatile portion was removed on the rotovap
  7. additionThe residue was diluted with 150 mL of EtOAc
  8. washwashed with saturated aqueous solution of sodium bicarbonate, and brine
  9. dry with materialThe resulting organic solution was then dried over magnesium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customPurification of the crude material on an ISCO 80 g column (60-100% EtOAc in hexanes)

출처 및 근거

ORD 기록
ord-e76ac1841d114f8aabc2b15d1f452ecb
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08367671B2

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