3-Aminopyridine → 3-[1-(N-isopropylglycyl)-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl]-5,5-dimethyl-1-{[2-(pyridin-3-ylamino)pyridin-4-yl]methyl}imidazolidine-2,4-dione

HRID 546610

反応式

HRID 546610 の反応式
Cl[C:2]1[CH:7]=[C:6]([CH2:8][N:9]2[C:13]([CH3:15])([CH3:14])[C:12](=[O:16])[N:11]([C:17]3[CH:25]=[C:24]4[C:20]([C:21]([CH3:34])([CH3:33])[CH2:22][N:23]4[C:26](=[O:32])[CH2:27][NH:28][CH:29]([CH3:31])[CH3:30])=[CH:19][CH:18]=3)[C:10]2=[O:35])[CH:5]=[CH:4][N:3]=1.[NH2:36][C:37]1[CH:38]=[N:39][CH:40]=[CH:41][CH:42]=1.CC1(C)C2C=CC(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=2OC2C1=CC=C(P(C1C=CC=CC=1)C1C=CC=CC=1)C=2.C(=O)([O-])[O-].[Cs+].[Cs+]>CN1CCCC1=O.ClCCl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:29]([NH:28][CH2:27][C:26]([N:23]1[C:24]2[C:20](=[CH:19][CH:18]=[C:17]([N:11]3[C:12](=[O:16])[C:13]([CH3:15])([CH3:14])[N:9]([CH2:8][C:6]4[CH:5]=[CH:4][N:3]=[C:2]([NH:36][C:37]5[CH:38]=[N:39][CH:40]=[CH:41][CH:42]=5)[CH:7]=4)[C:10]3=[O:35])[CH:25]=2)[C:21]([CH3:34])([CH3:33])[CH2:22]1)=[O:32])([CH3:31])[CH3:30]

参加物

8

反応物 4

HCID 100093-AminopyridineHCID 10796Cesium carbonateHCID 576259921-[(2-chloropyridin-4-yl)methyl]-3-[1-(N-isopropylglycyl)-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl]-5,5-dimethylimidazolidine-2,4-dioneHCID 86628973(9,9-dimethyl-9H-xanthene-3,6-diyl)bis(diphenylphosphine)

生成物 1

HCID 576260313-[1-(N-isopropylglycyl)-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl]-5,5-dimethyl-1-{[2-(pyridin-3-ylamino)pyridin-4-yl]methyl}imidazolidine-2,4-dione収率 12.6%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 6344Dichloromethane溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
140 °C

実験手順

To a solution of 249 mg of 1-[(2-chloropyridin-4-yl)methyl]-3-[1-(N-isopropylglycyl)-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl]-5,5-dimethylimidazolidine-2,4-dione obtained in stage a) below in 3 mL of N-methylpyrrolidinone are successively added, under argon, 94 mg of 3-aminopyridine, 29 mg of (9,9-dimethyl-9H-xanthene-3,6-diyl)bis(diphenylphosphine) (Xantphos), 22 mg of palladium acetate and 652 mg of caesium carbonate. The reaction mixture is heated at 140° C. for 1 hour by microwave, cooled to room temperature, diluted with 20 mL of dichloromethane and filtered, and the filtrate is concentrated under reduced pressure. The residue is triturated in 40 mL of water and the precipitate formed is filtered off and purified by chromatography on a column of silica, eluting with a mixture of dichloromethane and methanol (93/7 by volume) to give 35 mg of 3-[1-(N-isopropylglycyl)-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl]-5,5-dimethyl-1-{[2-(pyridin-3-ylamino)pyridin-4-yl]methyl}imidazolidine-2,4-dione, the characteristics of which are as follows:

後処理

  1. temperaturecooled to room temperature
  2. filtrationfiltered
  3. concentrationthe filtrate is concentrated under reduced pressure
  4. customThe residue is triturated in 40 mL of water
  5. customthe precipitate formed
  6. filtrationis filtered off
  7. custompurified by chromatography on a column of silica
  8. washeluting with a mixture of dichloromethane and methanol (93/7 by volume)

出典と根拠

ORDレコード
ord-3b40de847d8e458c9c38022bf8a6f693
出典データセット
uspto-grants-2011_05
特許番号
US07935819B2

関連ノート

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