Cesium carbonate → 3-[4-({3-[1-(N,N-dimethylglycyl)-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl]-5,5-dimethyl-2,4-dioxoimidazolidin-1-yl}methyl)-pyridin-2-yl]-1,1-dimethylurea

HRID 546609

반응식

HRID 546609 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.[CH3:35][N:36]([CH3:40])[C:37]([NH2:39])=[O:38].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+]>O1CCOCC1.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:39][C:37](=[O:38])[N:36]([CH3:40])[CH3:35])[CH:7]=4)[C:10]3=[O:34])[CH:25]=2)[C:21]([CH3:33])([CH3:32])[CH2:22]1)=[O:31]

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 11737N,N-DimethylureaHCID 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 576259763-[4-({3-[1-(N,N-dimethylglycyl)-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl]-5,5-dimethyl-2,4-dioxoimidazolidin-1-yl}methyl)-pyridin-2-yl]-1,1-dimethylurea수율 19.9%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 312751,4-Dioxane용매

실험 절차

To a solution of 242 mg of 1-(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-dione obtained in stage a) of Example 31B in 10 mL of dioxane are successively added, under argon, 33 mg of N,N-dimethylurea, 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 refluxed for 6 hours, cooled to room temperature, filtered and washed with three times 10 mL of dichloromethane, and the filtrate is concentrated under reduced pressure. The residue is triturated in 20 mL of water and the precipitate formed is filtered off and purified twice by chromatography on a column of silica, eluting with a mixture of dichloromethane and methanol (93/7 by volume) to give 40 mg of 3-[4-({3-[1-(N,N-dimethylglycyl)-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl]-5,5-dimethyl-2,4-dioxoimidazolidin-1-yl}methyl)-pyridin-2-yl]-1,1-dimethylurea, the characteristics of which are as follows:

후처리

  1. temperatureThe reaction mixture is refluxed for 6 hours
  2. filtrationfiltered
  3. washwashed with three times 10 mL of dichloromethane
  4. concentrationthe filtrate is concentrated under reduced pressure
  5. customThe residue is triturated in 20 mL of water
  6. customthe precipitate formed
  7. filtrationis filtered off
  8. custompurified twice by chromatography on a column of silica
  9. washeluting with a mixture of dichloromethane and methanol (93/7 by volume)

출처 및 근거

ORD 기록
ord-f96d97cfd9c345ddbe11d4bc0db1668e
출처 데이터셋
uspto-grants-2011_05
특허 번호
US07935819B2

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