Sodium Carbonate → N-methyl-1-(3-thien-2-ylphenyl)-1H-benzimidazole-5-carboxamide

HRID 28667Notes

Reaction equation

HRID 28667 reaction equation
Br[C:2]1[CH:3]=[C:4]([N:8]2[C:12]3[CH:13]=[CH:14][C:15]([C:17]([NH:19][CH3:20])=[O:18])=[CH:16][C:11]=3[N:10]=[CH:9]2)[CH:5]=[CH:6][CH:7]=1.[S:21]1[CH:25]=[CH:24][CH:23]=[C:22]1B(O)O.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:20][NH:19][C:17]([C:15]1[CH:14]=[CH:13][C:12]2[N:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([C:22]4[S:21][CH:25]=[CH:24][CH:23]=4)[CH:3]=3)[CH:9]=[N:10][C:11]=2[CH:16]=1)=[O:18]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27339602-Thiopheneboronic acidHCID 673693471-(3-bromophenyl)-N-methyl-1H-benzimidazole-5-carboxamide

Product 1

HCID 11638545N-methyl-1-(3-thien-2-ylphenyl)-1H-benzimidazole-5-carboxamide

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(3-bromophenyl)-N-methyl-1H-benzimidazole-5-carboxamide (20 mg, 0.06 mmol) and thiophene-2-boronic acid (9.0 mg. 0.073 mmol) in anhydrous DMF (0.6 mL) was added Pd(PPh3)4 (3.5 mg, 0.003 mmol) followed by a solution of Na2CO3 (19 mg, 0.18 mmol) in water (0.16 mL). The reaction was irradiated in the microwave for 10 min (200 W, 150° C.). After cooling, the reaction mixture was filtered through Celite and washed with EtOAc (15 mL). The combined organic layer was washed with saturated aqueous NaHCO3 solution (10 mL) followed by saturated aqueous solution brine (3×10 mL), dried (MgSO4) and evaporated to dryness. The crude product was purified by solid-phase extraction (Isolute SAX, followed by Isolute SCX), giving N-methyl-1-(3-thien-2-ylphenyl)-1H-benzimidazole-5-carboxamide as an off-white solid; 1H NMR (400 MHz, MeOH-d4): δ 8.57 (s, 1H), 8.27 (d, J=2 Hz, 1H), 7.89-7.86 (m, 2H), 7.78 (d, J=7.8 Hz, 1H), 7.66-7.62 (m, 2H), 7.52-7.54 (m, 2H), 7.45 (d, J=5.1 Hz, 1H), 7.12 (dd, J=3.5 Hz, 1.5 Hz, 1H), 2.97 (s, 3H); MS (ES+): m/z 333.9 (100%) [MH+].

Workup

  1. customThe reaction was irradiated in the microwave for 10 min (200 W, 150° C.)
  2. temperatureAfter cooling
  3. filtrationthe reaction mixture was filtered through Celite
  4. washwashed with EtOAc (15 mL)
  5. washThe combined organic layer was washed with saturated aqueous NaHCO3 solution (10 mL)
  6. dry with materialdried (MgSO4)
  7. customevaporated to dryness
  8. customThe crude product was purified by solid-phase extraction (Isolute SAX, followed by Isolute SCX)

Sources & evidence

ORD record
ord-4181985908194abfa800130886e71e98
Source dataset
uspto-grants-2008_09
Patent number
US07419995B2

Reaction notes

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