Water → 3-(3-Fluoro-4-pyridinylamino)-1H-indole hydrochloride

HRID 376871노트

반응식

HRID 376871 반응식
[NH2:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[NH:4][CH:3]=1.Cl.[Cl:12][C:13]1[CH:18]=[CH:17][N:16]=[CH:15][C:14]=1[F:19].O.C(=O)([O-])[O-].[Na+].[Na+]>CN1CCCC1=O>[ClH:12].[F:19][C:14]1[CH:15]=[N:16][CH:17]=[CH:18][C:13]=1[NH:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[NH:4][CH:3]=1

참가 물질

6

반응물 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 2302801H-indol-3-amineHCID 193602344-Chloro-3-fluoropyridine hydrochloride2회

생성물 1

HCID 193601303-(3-Fluoro-4-pyridinylamino)-1H-indole hydrochloride수율 121.7%

시약·촉매·용매 1

HCID 13387N-methyl-2-pyrrolidone용매

실험 절차

A solution of 3-aminoindole (7 g) and 4-chloro-3-fluoropyridine hydrochloride (13 g) in 200 mL of 1-methyl-2-pyrrolidinone was stirred at 75-80° C. for two hours, after which additional 4-chloro-3-fluoropyridine hydrochloride (5 g) was added. After stirring a total of three hours the mixture was cooled, stirred with water, basified with sodium carbonate and extracted with ethyl acetate. The dried (anhydrous magnesium sulfate) organic layer was filtered and concentrated to 20 g of a dark oil. Elution through silica gel first with dichloromethane and then with 50% ethyl acetate in dichloromethane via flash column chromatography yielded 17 g of a dark oil. This oil was eluted through silica with ether via flash column chromatography to yield 10.6 g of a dark oil. This oil was eluted through silica with 20% ethyl acetate in dichloromethane via HPLC to yield 8 g of a dark oil. A six gram portion was converted to the hydrochloride salt in methanol/ether to yield 3.5 g of a solid, m.p. >250° C. Recrystallization from 30% methanol in ether yielded 2.7 g of crystals, m.p. 256-258° C. (dec.).

후처리

  1. temperaturewas cooled
  2. extractionextracted with ethyl acetate
  3. dry with materialThe dried (anhydrous magnesium sulfate) organic layer
  4. filtrationwas filtered
  5. concentrationconcentrated to 20 g of a dark oil
  6. washElution through silica gel first with dichloromethane

출처 및 근거

ORD 기록
ord-2ac882812dc2475399bc318c639c80e5
출처 데이터셋
uspto-grants-2000_02
특허 번호
US06022880

반응 노트

불러오는 중…