Cesium carbonate → 3-(Benzyloxy)-1-methyl-5-(4-phenyl-1H-imidazol-1-yl)pyridin-2(1H)-one

HRID 625949ノート

反応式

HRID 625949 の反応式
[CH2:1]([O:8][C:9]1[C:10](=[O:17])[N:11]([CH3:16])[CH:12]=[C:13](Br)[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:18]1([C:24]2[N:25]=[CH:26][NH:27][CH:28]=2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C([O-])([O-])=O.[Cs+].[Cs+].CNC1CCCCC1NC>CN(C=O)C.[Cu]I>[CH2:1]([O:8][C:9]1[C:10](=[O:17])[N:11]([CH3:16])[CH:12]=[C:13]([N:27]2[CH:28]=[C:24]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[N:25]=[CH:26]2)[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 5510741-N,2-N-dimethylcyclohexane-1,2-diamine2 回HCID 674178603-(benzyloxy)-5-bromo-1-methylpyridin-2(1H)-oneHCID 178418822HCID 178418822、化合物

生成物 1

HCID 699362433-(Benzyloxy)-1-methyl-5-(4-phenyl-1H-imidazol-1-yl)pyridin-2(1H)-one収率 53%

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒2 回HCID 6228Dimethylformamide溶媒

反応条件

温度
110 °C

実験手順

3-(Benzyloxy)-5-bromo-1-methylpyridin-2(1H)-one (50 mg, 0.170 mmol), 4-phenylimidazole (29 mg, 0.201 mmol), Cs2CO3 (111 mg, 0.340 mmol), CuI (2 mg, 10.50 μmol), and N,N′-dimethyl-1,2-cyclohexanediamine (6 μl, 0.038 mmol) were combined in DMF (0.5 mL) in a screw cap vial. The vial was sealed then heated to 110° C. After stirring overnight the mixture was cooled to RT. CuI (2 mg) and N,N′-dimethyl-1,2-cyclohexanediamine (6 uL) were added and heating continued at 110° C. After 6 h the mixture was cooled to RT. The mixture was filtered using a 0.45 μm PTFE syringe filter then purified by preparative reversed-phase HPLC (20×150 mm Waters Sunfire (0.1% TFA), 5-50% CH3CN/water over 20 min at 20 mL/min). Fractions containing the product were pooled then passed through Dowex 1×2-400 ion exchange resin (prewashed with 1M NaOH, H2O, MeOH) washing with MeOH. The filtrate was concentrated to give the title compound (32 mg, 53%) as an amber film. 1H NMR (500 MHz, CDCl3): δ 7.78 (d, J=7.7 Hz, 2 H); 7.59 (s, 1 H); 7.45-7.36 (m, 9 H); 7.13 (d, J=2.5 Hz, 1 H); 6.73 (d, J=2.5 Hz, 1 H); 5.19 (s, 2 H); 3.65 (s, 3 H). LC/MS (M+H)+ 358.

後処理

  1. customcap vial
  2. customThe vial was sealed
  3. temperaturewas cooled to RT
  4. temperatureheating
  5. customcontinued at 110° C
  6. temperatureAfter 6 h the mixture was cooled to RT
  7. filtrationThe mixture was filtered
  8. filtrationfilter
  9. customthen purified by preparative reversed-phase HPLC (20×150 mm Waters Sunfire (0.1% TFA), 5-50% CH3CN/water over 20 min at 20 mL/min)
  10. additionFractions containing the product
  11. washwashing with MeOH
  12. concentrationThe filtrate was concentrated

出典と根拠

ORDレコード
ord-124be449038e493ea8493ad484568fae
出典データセット
uspto-grants-2016_04
特許番号
US09309199B2

反応ノート

読み込み中…