N,N'-Dicyclohexylurea → HCID 10345144、化合物

HRID 2357505ノート

反応式

HRID 2357505 の反応式
ON1C2C=CC=CC=2N=N1.[NH:11]1[CH2:15][CH2:14][CH:13]([C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[NH:18][CH:17]=2)[CH2:12]1.CN1CCOCC1.[CH3:32][N:33]([CH3:51])[C:34]1([C:44]2[CH:49]=[CH:48][C:47]([F:50])=[CH:46][CH:45]=2)[CH2:39][CH2:38][C:37](=[CH:40][C:41](O)=[O:42])[CH2:36][CH2:35]1.C1(N=C=NC2CCCCC2)CCCCC1.C(NC1CCCCC1)(NC1CCCCC1)=O.[OH-].[Na+]>CN(C)C=O.O>[CH3:51][N:33]([CH3:32])[C:34]1([C:44]2[CH:45]=[CH:46][C:47]([F:50])=[CH:48][CH:49]=2)[CH2:39][CH2:38][C:37](=[CH:40][C:41]([N:11]2[CH2:15][CH2:14][CH:13]([C:16]3[C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[NH:18][CH:17]=3)[CH2:12]2)=[O:42])[CH2:36][CH2:35]1

参加物

10

反応物 7

HCID 4277N,N'-DicyclohexylureaHCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 184096763-(pyrrolidin-3-yl)-1H-indoleHCID 67386288[4-Dimethylamino-4-(4-fluorophenyl)-cyclohexylidene)-acetic acid

生成物 1

HCID 10345144HCID 10345144、化合物収率 52%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

1-hydroxybenzotriazole (1.08 mg, 8 mmole), 3-pyrrolidine-3-yl-1H-indole (744 mg, 4 mmole) and N-methylmorpholine (0.888 ml, 8 mmole) were added in succession under argon to a solution of [4-dimethylamino-4-(4-fluorophenyl)-cyclohexylidene)-acetic acid (1.055 g, 4 mmole) in dry dimethylformamide (40 ml). The clear solution was cooled in an ice bath and dicyclohexylcarbodiimide (1.65 g, 8 mmole) was added. The reaction mixture was stirred for 5 days at room temperature, the dicyclohexylurea precipitating out little by little. The reaction mixture was worked up by separating the precipitated urea and adding the filtrate to a mixture of saturated NaCl solution (40 ml) and saturated NaHCO3 solution (10 ml). Further urea thereupon precipitated out, which was separated. The filtrate was diluted with water (300 ml) and 5M sodium hydroxide (7 ml, 35 mmole) was added. The crude product of 2-(4-dimethylamino-4-(4-fluorophenyl)cyclohexylidene)-1-[3-(1H-indol-3-yl)pyrrolidine-1-yl]-ethanone thereupon precipitated out as a beige-coloured solid (1.67 g). The chromatographic separation on silica gel (80 g) was carried out with EE/methanol (1:1). 2-(4-dimethylamino-4-(4-fluorophenyl)cyclohexylidene)-1-[3-(1H-indol-3-yl)pyrrolidine-1-yl]-ethanone was thereby obtained as a diastereoisomer mixture in a yield of 52% (916 mg) in the form of a colourless solid with a melting point of 109°-112° C.

後処理

  1. temperatureThe clear solution was cooled in an ice bath
  2. customby separating the precipitated urea
  3. additionadding the filtrate
  4. additionto a mixture of saturated NaCl solution (40 ml) and saturated NaHCO3 solution (10 ml)
  5. customFurther urea thereupon precipitated out
  6. customwhich was separated
  7. additionwas added
  8. customThe crude product of 2-(4-dimethylamino-4-(4-fluorophenyl)cyclohexylidene)-1-[3-(1H-indol-3-yl)pyrrolidine-1-yl]-ethanone thereupon precipitated out as a beige-coloured solid (1.67 g)
  9. customThe chromatographic separation on silica gel (80 g)

出典と根拠

ORDレコード
ord-2e52962d14994765a3a2d19e72997bbb
出典データセット
uspto-grants-2010_07
特許番号
US07759385B2

反応ノート

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