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

HRID 1425809Notes

Reaction equation

HRID 1425809 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, 1H), 8.05 (d, J=8.4 Hz, 1H), 7.84 (d, J=7.2 Hz, 1H), 7.74-7.72 (m, 1H), 7.64 (d, J=7.6 Hz, 1H), 7.59-7.56 (m, 1H), 7.11-7.05 (m, 4H), 6.93 (d, J=7.2 Hz, 2H), 6.82 (d, J=7.6 Hz, 2H), 5.39 (s, 2H), 3.81 (s, 3H), 3.19 (s, 6H). 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-c483ab8d1a794152a4ee5a453f7a1571
Source dataset
uspto-grants-2015_01
Patent number
US08933074B2

Reaction notes

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