1,1'-Carbonyldiimidazole → 2-(3-[1,3]dioxolan-2-ylmethylphenyl)-1H-benzimidazole-4-carboxamide

HRID 2374678Notes

Reaction equation

HRID 2374678 reaction equation
[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[CH2:6][C:7]1[CH:8]=[C:9]([CH:13]=[CH:14][CH:15]=1)[C:10](O)=O.C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.Cl.[NH2:30][C:31]1[C:39]([NH2:40])=[CH:38][CH:37]=[CH:36][C:32]=1[C:33]([NH2:35])=[O:34]>N1C=CC=CC=1.CN(C)C=O>[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[CH2:6][C:7]1[CH:8]=[C:9]([C:10]2[NH:40][C:39]3[CH:38]=[CH:37][CH:36]=[C:32]([C:33]([NH2:35])=[O:34])[C:31]=3[N:30]=2)[CH:13]=[CH:14][CH:15]=1

Participants

6

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 247269923-(1,3-Dioxolan-2-ylmethyl)benzoic acidHCID 534228072,3-Diaminobenzamide dihydrochloride

Product 1

HCID 685329682-(3-[1,3]dioxolan-2-ylmethylphenyl)-1H-benzimidazole-4-carboxamide

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 3-(1,3-dioxolan-2-ylmethyl)benzoic acid (1.0 g, 4.80 mmol) in a mixture of pyridine (5 mL) and N,N-dimethylformamide (5 mL) was treated with 1,1′-carbonyldiimidazole (0.856 g, 5.28 mmol) at 45° C. for 2 hours. 2,3-diaminobenzamide dihydrochloride (synthesized as described in U.S. Pat. No. 6,737,421, column 11, EXAMPLE 2, step (e), 1.08 g, 4.80 mmol) was added and the mixture stirred at ambient temperature overnight. The mixture was concentrated and the residue purified by flash chromatography on silica gel with 10% methanol in 2:1 ethyl acetate/hexane. The product was dissolved in acetic acid (20 mL) and the solution heated at 60° C. for 2 hours and at 80° C. for 1.5 hours, cooled and concentrated and the residue partitioned between ethyl acetate and sodium bicarbonate solution. The organic phase was concentrated and the residue purified on silica gel with 10% methanol in 2:1 ethyl acetate/hexane to give 1.13 g of the title compound. MS (APCI) m/z 324 (M+H)+.

Workup

  1. addition6,737,421, column 11, EXAMPLE 2, step (e), 1.08 g, 4.80 mmol) was added
  2. concentrationThe mixture was concentrated
  3. customthe residue purified by flash chromatography on silica gel with 10% methanol in 2:1 ethyl acetate/hexane
  4. dissolutionThe product was dissolved in acetic acid (20 mL)
  5. temperaturethe solution heated at 60° C. for 2 hours and at 80° C. for 1.5 hours
  6. temperaturecooled
  7. concentrationconcentrated
  8. customthe residue partitioned between ethyl acetate and sodium bicarbonate solution
  9. concentrationThe organic phase was concentrated
  10. customthe residue purified on silica gel with 10% methanol in 2:1 ethyl acetate/hexane

Sources & evidence

ORD record
ord-122f71de75334f9e97dce1aa73f82b77
Source dataset
uspto-grants-2008_12
Patent number
US07462724B2

Reaction notes

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