Potassium Carbonate → (4-(1-((R)-1-(2,4-dichlorophenyl)ethyl)-1H-benzo[d]imidazol-6-yl)-5,6-dihydropyridin-1(2H)-yl)((R)-piperidin-2-yl)methanone

HRID 2359118ノート

反応式

HRID 2359118 の反応式
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[CH:8][N:7]([C@@H:10]([C:12]3[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=3[Cl:19])[CH3:11])[C:6]=2[CH:20]=1.C(O[C:26]([N:28]1[CH2:33][CH:32]=[C:31](B(O)O)[CH2:30][CH2:29]1)=[O:27])(C)(C)C.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:19][C:13]1[CH:14]=[C:15]([Cl:18])[CH:16]=[CH:17][C:12]=1[C@H:10]([N:7]1[C:6]2[CH:20]=[C:2]([C:31]3[CH2:30][CH2:29][N:28]([C:26]([C@H:29]4[CH2:30][CH2:31][CH2:32][CH2:33][NH:28]4)=[O:27])[CH2:33][CH:32]=3)[CH:3]=[CH:4][C:5]=2[N:9]=[CH:8]1)[CH3:11]

参加物

7

反応物 3

HCID 11430Potassium CarbonateHCID 21931462(1-(tert-Butoxycarbonyl)-1,2,3,6-tetrahydropyridin-4-yl)boronic acidHCID 86688429(R)-6-bromo-1-(1-(2,4-dichlorophenyl)ethyl)-1H-benzo[d]imidazole

生成物 1

HCID 71569868(4-(1-((R)-1-(2,4-dichlorophenyl)ethyl)-1H-benzo[d]imidazol-6-yl)-5,6-dihydropyridin-1(2H)-yl)((R)-piperidin-2-yl)methanone

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 702Ethanol溶媒HCID 1140Toluene溶媒

反応条件

温度
100 °C

実験手順

A mixture of (R)-6-bromo-1-(1-(2,4-dichlorophenyl)ethyl)-1H-benzo[d]imidazole (1.3 g, 3.5 mmol), (N-t-butoxycarbonyl-1,2,3,6-tetrahydropyridin-4-yl)boronic acid pincol ester (1.2 g, 3.9 mmol), tetrakis(triphenylphosphine)palladium(0) (Pd(PPh3)4, 0.20 g, 0.18 mmol), and 2 M aqueous potassium carbonate (5.3 mL, 10.5 mmol) in toluene (10 mL) and ethanol (5 mL). The mixture was purged with nitrogen for 5 min, and then heated at 100° C. for 2 h. After cooling to room temperature, the mixture was extracted with ethyl acetate (20 mL). The organic layer was washed with brine, dried (Na2SO4), and concentrated in vacuo. The resulting crude material was purified by flash chromatography (SiO2, 0-100% ethyl acetate in hexanes) to afford the desired product in 90% purity (1.6 g, 3.4 mmol, 97%). MS: (ES) m/z calculated for C25H28Cl2N3O [M+H]+ 472.2. found 472.

後処理

  1. customThe mixture was purged with nitrogen for 5 min
  2. temperatureAfter cooling to room temperature
  3. extractionthe mixture was extracted with ethyl acetate (20 mL)
  4. washThe organic layer was washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe resulting crude material was purified by flash chromatography (SiO2, 0-100% ethyl acetate in hexanes)

出典と根拠

ORDレコード
ord-5c2ccf33a0b7435cbb04ec64cea5f4b5
出典データセット
uspto-grants-2014_04
特許番号
US08685959B2

反応ノート

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