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

HRID 1645825ノート

反応式

HRID 1645825 の反応式
[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

参加物

6

反応物 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 2302801H-indol-3-amineHCID 193602344-Chloro-3-fluoropyridine hydrochloride2 回

生成物 1

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

試薬・触媒・溶媒 1

HCID 13387N-methyl-2-pyrrolidone溶媒

実験手順

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.).

後処理

  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

出典と根拠

ORDレコード
ord-eebd6f0ed1eb4cca9235670b3e4ccb25
出典データセット
uspto-grants-1993_01
特許番号
US05177088

反応ノート

読み込み中…