Potassium Carbonate → (4-(3-chloropyrazin-2-yloxy)phenyl)(1H-benzo[d]imidazol-2-yl)methanone

HRID 2191923Notes

Reaction equation

HRID 2191923 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]([C:12]1[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=1)=[O:11].C([O-])([O-])=O.[K+].[K+].[Cl:25][C:26]1[C:31](Cl)=[N:30][CH:29]=[CH:28][N:27]=1.CC(OC)(C)C.C(Cl)Cl>CN(C=O)C>[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]([C:12]1[CH:17]=[CH:16][C:15]([O:18][C:31]2[C:26]([Cl:25])=[N:27][CH:28]=[CH:29][N:30]=2)=[CH:14][CH:13]=1)=[O:11]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 785752,3-DichloropyrazineHCID 21918119Dcm mtbeHCID 59326874(1H-benzo[d]imidazol-2-yl)(4-hydroxyphenyl)methanone

Product 1

HCID 46207940(4-(3-chloropyrazin-2-yloxy)phenyl)(1H-benzo[d]imidazol-2-yl)methanone

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of compound (1H-benzo[d]imidazol-2-yl)(4-hydroxyphenyl)methanone (100 g, 0.42 mol) in anhydrous DMF (1.1 L) was added K2CO3 (145 g, 1.05 mol, 2.5 eq.) and 2,3-dichloropyrazine (75.08 g, 0.50 mol, 1.2 eq.). The reaction was stirred at 90° C. for 18 h. LCMS analysis of the reaction mixture showed that the reaction was complete. The reaction mixture was cooled to ambient temperature and ice-water (3 L) was added, stirred for 30 minutes. The resulting solid was filtered and washed with water (3 L) followed by MTBE (2×500 mL) and dried under vacuum. The solid was treated with 50% MTBE/DCM at 50° C. for 1 h and filtered hot, washed with 50% MTBE/DCM and dried under vacuum overnight to obtain product. Mother liquor was refluxed with 50% MTBE/DCM for 2 h and filtered hot and washed with 50% MTBE/DCM to get another batch of product. MS (ESI, pos. ion) m/z: 351.0 (M+1). IC50 (uM) +.

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. stirringstirred for 30 minutes
  3. filtrationThe resulting solid was filtered
  4. washwashed with water (3 L)
  5. customdried under vacuum
  6. additionThe solid was treated with 50% MTBE/DCM at 50° C. for 1 h
  7. filtrationfiltered hot
  8. washwashed with 50% MTBE/DCM
  9. customdried under vacuum overnight
  10. customto obtain product
  11. filtrationfiltered hot
  12. washwashed with 50% MTBE/DCM
  13. customto get another batch of product

Sources & evidence

ORD record
ord-e27b90ab0aaa4e329a23d65732fc8daa
Source dataset
uspto-grants-2012_12
Patent number
US08329700B2

Reaction notes

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