Potassium Carbonate → HCID 86281646, compound

HRID 1776737Notes

Reaction equation

HRID 1776737 reaction equation
[CH3:1][C:2]([CH3:28])([CH2:6][C:7]1[NH:11][C:10]2[CH:12]=[CH:13][C:14]([O:16][CH2:17][C:18]3[CH:27]=[CH:26][C:25]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[N:19]=3)=[CH:15][C:9]=2[N:8]=1)[C:3]([OH:5])=[O:4].Br[CH2:30][C:31]1[CH:39]=[CH:38][C:34]2=[N:35][O:36][N:37]=[C:33]2[CH:32]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[N:35]1[O:36][N:37]=[C:33]2[CH:32]=[C:31]([CH2:30][N:11]3[C:10]4[CH:12]=[CH:13][C:14]([O:16][CH2:17][C:18]5[CH:27]=[CH:26][C:25]6[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=6)[N:19]=5)=[CH:15][C:9]=4[N:8]=[C:7]3[CH2:6][C:2]([CH3:28])([CH3:1])[C:3]([OH:5])=[O:4])[CH:39]=[CH:38][C:34]=12

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27355875-(Bromomethyl)-2,1,3-benzoxadiazoleHCID 178441531HCID 178441531, compound

Product 1

HCID 86281646HCID 86281646, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A suspension of 2,2-dimethyl-3-(5-(quinolin-2-ylmethoxy)-1H-benzo[d]imidazol-2-yl)propanoic acid (300 mg, 0.75 mmol), 5-(bromomethyl)benzo[c][1,2,5]oxadiazole (168 mg, 0.75 mmol) and potassium carbonate (310 mg, 2.25 mmol) in DMF (20 mL) was heated to 70° C. for 18 h. The mixture was cooled to RT and concentrated to dryness. The residue was dissolved in THF/MeOH (18 mL, 1:1) and treated with 5% aq. NaOH (2 mL). The mixture was stirred at 40° C. for 16 h. The reaction was allowed to cool to RT and then concentrated to dryness. The residue was diluted with water (30 mL), washed with EtOAc (20 mL), and then treated with 6N aq. HCl to ˜pH 6. The aqueous was then extracted with DCM (2×30 mL). The organics were combined, dried with Na2SO4, filtered and concentrated to dryness. The residue was purified by reverse phase HPLC to afford the title compound. MS (ESI): mass calcd. for C29H26N6O4, 507.19; m/z found, 507.9 [M+H]+. 1H NMR (300 MHz, DMSO-d6) δ 8.44 (d, J=8.6, 1H), 8.11-7.98 (m, 3H), 7.85-7.77 (m, 1H), 7.71 (d, J=8.5, 1H), 7.68-7.61 (m, 2H), 7.58-7.52 (m, 1H), 3.35-3.33 (m, 2H), 7.50-7.43 (m, 1H), 7.38-7.33 (m, 1H), 7.21-7.12 (m, 1H), 5.84 (s, 2H), 5.47 (s, 2H), 1.30 (s, 6H).

Workup

  1. temperatureThe mixture was cooled to RT
  2. concentrationconcentrated to dryness
  3. dissolutionThe residue was dissolved in THF/MeOH (18 mL, 1:1)
  4. additiontreated with 5% aq. NaOH (2 mL)
  5. temperatureto cool to RT
  6. concentrationconcentrated to dryness
  7. additionThe residue was diluted with water (30 mL)
  8. washwashed with EtOAc (20 mL)
  9. additiontreated with 6N aq. HCl
  10. extractionThe aqueous was then extracted with DCM (2×30 mL)
  11. dry with materialdried with Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated to dryness
  14. customThe residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-88de38487cf14451838c2929196f9ff7
Source dataset
uspto-grants-2016_02
Patent number
US09265770B2

Reaction notes

Loading…