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

HRID 1673145Notes

Reaction equation

HRID 1673145 reaction equation
[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[CH2:6][C:7]1[CH:15]=[CH:14][C:10]([C:11](O)=O)=[CH:9][CH:8]=1.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:15]=[CH:14][C:10]([C:11]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:9][CH:8]=1

Participants

6

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 247269914-(1,3-Dioxolan-2-ylmethyl)benzoic acidHCID 534228072,3-Diaminobenzamide dihydrochloride

Product 1

HCID 673532482-(4-[1,3]-Dioxolan-2-ylmethylphenyl)-1H-benzimidazole-4-carboxamide

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 4-(1,3-dioxolan-2-ylmethyl)benzoic acid (1.0 g, 4.80 mmol) in 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 heated in acetic acid (30 mL) at 80° C. for 3 hours. After cooling, the mixture was concentrated and the residue partitioned between ethyl acetate and sodium bicarbonate solution. After filtering, the filtrate was concentrated and the residue purified by flash chromatography on silica gel (0-15% methanol in 2:1 ethyl acetate/hexane) to give 1.14 g of the title compound. MS (DCI) 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. temperaturethe residue heated in acetic acid (30 mL) at 80° C. for 3 hours
  4. temperatureAfter cooling
  5. concentrationthe mixture was concentrated
  6. customthe residue partitioned between ethyl acetate and sodium bicarbonate solution
  7. filtrationAfter filtering
  8. concentrationthe filtrate was concentrated
  9. customthe residue purified by flash chromatography on silica gel (0-15% methanol in 2:1 ethyl acetate/hexane)

Sources & evidence

ORD record
ord-2fe37a1f41394aca875be80c8390741f
Source dataset
uspto-grants-2011_08
Patent number
US07999117B2

Reaction notes

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