N-methyl-2-pyrrolidone → 1-[(3-Fluoro-4-pyridinyl)amino]-3-methyl-5-(phenylmethoxy)-1H-indole

HRID 1029736노트

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HRID 1029736 반응식
[CH3:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([O:11][CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH:9]=2)[N:4]([NH2:19])[CH:3]=1.CN1CCCC1=O.Cl.Cl[C:29]1[CH:34]=[CH:33][N:32]=[CH:31][C:30]=1[F:35].C(=O)(O)[O-].[Na+]>C(OCC)(=O)C>[F:35][C:30]1[CH:31]=[N:32][CH:33]=[CH:34][C:29]=1[NH:19][N:4]1[C:5]2[C:10](=[CH:9][C:8]([O:11][CH2:12][C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)=[CH:7][CH:6]=2)[C:2]([CH3:1])=[CH:3]1

참가 물질

6

반응물 4

HCID 13387N-methyl-2-pyrrolidoneHCID 516892Sodium BicarbonateHCID 193602344-Chloro-3-fluoropyridine hydrochlorideHCID 199004803-methyl-5-(phenylmethoxy)-1H-indol-1-amine

생성물 1

HCID 199004651-[(3-Fluoro-4-pyridinyl)amino]-3-methyl-5-(phenylmethoxy)-1H-indole수율 60.5%

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

반응 조건

온도
80 °C

실험 절차

To a solution consisting of 3-methyl-5-(phenylmethoxy)-1H-indol-1-amine (4.81 g) and 1-methyl-2-pyrrolidinone (83 ml) was added 4-chloro-3-fluoro pyridine hydrochloride (3.20 g). The resulting mixture was heated at 80° C. for 2 hours. Upon cooling to room temperature, dilute aqueous sodium bicarbonate and ethyl acetate were added to the reaction mixture. The layers were separated and the aqueous phase was extracted with EtOAc (3x). The combined organic layers were washed successively with water (2x) and brine (1x), and thereafter dried (MgSO4). Filtration and concentration gave the crude product. Purification via flash column chromatography (silica gel, 50% ethyl acetate/dichloromethane) afforded 4.0 g of the desired product as a solid, m.p. 210°-213° C.

후처리

  1. temperatureUpon cooling to room temperature
  2. customThe layers were separated
  3. extractionthe aqueous phase was extracted with EtOAc (3x)
  4. washThe combined organic layers were washed successively with water (2x) and brine (1x)
  5. dry with materialdried (MgSO4)
  6. filtrationFiltration and concentration
  7. customgave the crude product
  8. customPurification via flash column chromatography (silica gel, 50% ethyl acetate/dichloromethane)

출처 및 근거

ORD 기록
ord-955271f5865940cca5a7f76918920b6f
출처 데이터셋
uspto-grants-1992_04
특허 번호
US05102891

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