3-Furoic acid → 2-(2,6-Dichlorophenylamino)-1-methyl-7-furan-3-yl-1,8-dihydro-9H-imidazo[4,5-f]quinazoline-9-one

HRID 2296718Notes

Reaction equation

HRID 2296718 reaction equation
[O:1]1[CH:5]=[CH:4][C:3]([C:6](O)=O)=[CH:2]1.OC1C2N=NNC=2C=CC=1.Cl.CN(C)CCCN=C=NCC.[NH2:31][C:32]1[CH:50]=[CH:49][C:35]2[N:36]=[C:37]([NH:40][C:41]3[C:46]([Cl:47])=[CH:45][CH:44]=[CH:43][C:42]=3[Cl:48])[N:38]([CH3:39])[C:34]=2[C:33]=1[C:51]([NH2:53])=[O:52]>CN(C=O)C.CCOC(C)=O>[Cl:48][C:42]1[CH:43]=[CH:44][CH:45]=[C:46]([Cl:47])[C:41]=1[NH:40][C:37]1[N:38]([CH3:39])[C:34]2=[C:33]3[C:32](=[CH:50][CH:49]=[C:35]2[N:36]=1)[N:31]=[C:6]([C:3]1[CH:4]=[CH:5][O:1][CH:2]=1)[NH:53][C:51]3=[O:52]

Participants

7

Reactant 4

HCID 102683-Furoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 113939665-Amino-2-(2,6-dichlorophenylamino)-3-methyl-3H-benzoimidazole-4-carboxylic acid amideHCID 178418300HCID 178418300, compound

Product 1

HCID 1354499902-(2,6-Dichlorophenylamino)-1-methyl-7-furan-3-yl-1,8-dihydro-9H-imidazo[4,5-f]quinazoline-9-one

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Furan-3-carboxylic acid (20 mg, 0.18 mmol), hydroxybenzotriazole (24 mg, 0.18 mmol) and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (35 mg, 0.18 mmol) were stirred together in DMF (1 mL) for 15 min. 5-Amino-2-(2,6-dichlorophenylamino)-3-methyl-3H-benzoimidazole-4-carboxylic acid amide (Example 7)(50 mg, 0.15 mmol) was added, and stirring continued for 24 h. The solution was diluted with EtOAc and washed in turn with aqueous Na2CO3, water and brine. The organic layer was evaporated and the residue dissolved in MeOH (2 mL). Sodium methoxide in MeOH (25%, 0.1 mL) was added and the solution heated to reflux for 45 min. The cooled solution was partitioned between water and CH2Cl2. The organic layer was evaporated and the crude product stirred with MeOH (1 mL) for 1 h. The solid was filtered, washed with a few drops of MeOH and dried to yield the title compound, 8 (14 mg, 22%). mp>300° C. MS (ES) 428, 426 (MH+).

Workup

  1. washwashed in turn with aqueous Na2CO3, water and brine
  2. customThe organic layer was evaporated
  3. dissolutionthe residue dissolved in MeOH (2 mL)
  4. additionSodium methoxide in MeOH (25%, 0.1 mL) was added
  5. temperaturethe solution heated
  6. temperatureto reflux for 45 min
  7. customThe cooled solution was partitioned between water and CH2Cl2
  8. customThe organic layer was evaporated
  9. stirringthe crude product stirred with MeOH (1 mL) for 1 h
  10. filtrationThe solid was filtered
  11. washwashed with a few drops of MeOH
  12. customdried

Sources & evidence

ORD record
ord-75f2c4af94ea4f64a5863debf87bf745
Source dataset
uspto-grants-2002_12
Patent number
US06489328B2

Reaction notes

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