Potassium Carbonate → 4-(4-methoxyphenyl)-1,3-dimethyl-5-(4-(quinolin-2-ylmethoxy)phenyl)-1H-imidazol-2(3H)-one

HRID 1258271Notes

Reaction equation

HRID 1258271 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]([CH3:23])[C:10](=[O:22])[N:11]([CH3:21])[C:12]=2[C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].Cl.Cl[CH2:32][C:33]1[CH:42]=[CH:41][C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[N:34]=1>>[CH3:20][O:19][C:16]1[CH:15]=[CH:14][C:13]([C:12]2[N:11]([CH3:21])[C:10](=[O:22])[N:9]([CH3:23])[C:8]=2[C:5]2[CH:6]=[CH:7][C:2]([O:1][CH2:32][C:33]3[CH:42]=[CH:41][C:40]4[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=4)[N:34]=3)=[CH:3][CH:4]=2)=[CH:18][CH:17]=1

Participants

4

Reactant 3

HCID 11430Potassium CarbonateHCID 30838232-(Chloromethyl)quinoline hydrochlorideHCID 593547664-(4-hydroxyphenyl)-5-(4-methoxyphenyl)-1,3-dimethyl-1H-imidazol-2(3H)-one

Product 1

HCID 593547624-(4-methoxyphenyl)-1,3-dimethyl-5-(4-(quinolin-2-ylmethoxy)phenyl)-1H-imidazol-2(3H)-oneYield 39.5%

Conditions

Temperature
80 °C

Procedure

To a stirred solution of 4-(4-hydroxyphenyl)-5-(4-methoxyphenyl)-1,3-dimethyl-1H-imidazol-2(3H)-one (0.35 g, 1.12 mmol) in AcN (20 mL) was added K2CO3 (0.46 g, 3.3 mmol) at RT. The reaction mixture was heated to 80° C. for 30 min, and then 2-(chloromethyl)quinoline hydrochloride (0.29 g, 1.35 mmol) was added and the mixture stirred for an additional 3 h at 80° C. Then the mixture was concentrated in vacuo and the residue was dissolved in EtOAc (30 mL). The organic layer was washed with water, dried over Na2SO4, filtered, and then concentrated in vacuo to obtain the crude product. The crude material was purified via silica gel column chromatography eluting with 80% EtOAc/20% hexanes to afford 4-(4-methoxyphenyl)-1,3-dimethyl-5-(4-(quinolin-2-ylmethoxy)phenyl)-1H-imidazol-2(3H)-one (0.2 g, 39%) as a solid. 1H NMR (500 MHz, CDCl3): δ 8.21 (d, J=7.2 Hz, 1 H), 8.05 (d, J=8.4 Hz, 1 H), 7.84 (d, J=7.2 Hz, 1 H), 7.74-7.72 (m, 1 H), 7.64 (d, J=7.6 Hz, 1 H), 7.59-7.56 (m, 1 H), 7.11-7.05 (m, 4 H), 6.93 (d, J=7.2 Hz, 2 H), 6.82 (d, J=7.6 Hz, 2 H), 5.39 (s, 2 H), 3.81 (s, 3 H), 3.19 (s, 6 H). MS: M+H: m/z=452.2 and HPLC: 97%, (Condition-H).

Workup

  1. concentrationThen the mixture was concentrated in vacuo
  2. dissolutionthe residue was dissolved in EtOAc (30 mL)
  3. washThe organic layer was washed with water
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto obtain the crude product
  8. customThe crude material was purified via silica gel column chromatography
  9. washeluting with 80% EtOAc/20% hexanes

Sources & evidence

ORD record
ord-33f26e94d1ba4533b4f7b6b0b027cdc6
Source dataset
uspto-grants-2013_06
Patent number
US08466148B2

Reaction notes

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