3-Aminopyridine → 3-[1-(N,N-dimethylglycyl)-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 546607

반응식

HRID 546607 반응식
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]([CH3:33])([CH3:32])[CH2:22][N:23]4[C:26](=[O:31])[CH2:27][N:28]([CH3:30])[CH3:29])=[CH:19][CH:18]=3)[C:10]2=[O:34])[CH:5]=[CH:4][N:3]=1.[NH2:35][C:36]1[CH:37]=[N:38][CH:39]=[CH:40][CH:41]=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>[CH3:29][N:28]([CH3:30])[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:35][C:36]5[CH:37]=[N:38][CH:39]=[CH:40][CH:41]=5)[CH:7]=4)[C:10]3=[O:34])[CH:25]=2)[C:21]([CH3:33])([CH3:32])[CH2:22]1)=[O:31]

참가 물질

8

반응물 4

HCID 100093-AminopyridineHCID 10796Cesium carbonateHCID 576260011-(2-chloropyridin-4-ylmethyl)-3-[1-(2-dimethylamino-acetyl)-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl]-5,5-dimethyl-imidazolidine-2,4-dioneHCID 86628973(9,9-dimethyl-9H-xanthene-3,6-diyl)bis(diphenylphosphine)

생성물 1

HCID 576260243-[1-(N,N-dimethylglycyl)-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-dione수율 27.7%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 6344Dichloromethane용매HCID 13387N-methyl-2-pyrrolidone용매

반응 조건

온도
140 °C

실험 절차

To a solution of 242 mg of 1-[(2-chloropyridin-4-yl)methyl]-3-[1-(N,N-dimethylglycyl)-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl]-5,5-dimethylimidazolidine-2,4-dione obtained in stage a) below in 2 mL of N-methylpyrrolidinone are successively added, under argon, 70 mg of 3-aminopyridine, 29 mg of (9,9-dimethyl-9H-xanthene-3,6-diyl)bis(diphenylphosphine) (Xantphos), 11 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 10 mL of dichloromethane and filtered, and the filtrate is concentrated under reduced pressure. The residue is taken up in 30 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 75 mg of 3-[1-(N,N-dimethylglycyl)-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:

후처리

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

출처 및 근거

ORD 기록
ord-d0d7df76b2b34daabe922e5b8370743e
출처 데이터셋
uspto-grants-2011_05
특허 번호
US07935819B2

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