Water → 4,5-Difluoro-3-(2-fluoro-4-iodophenyl)-1H-benzofuro[6,7-d]imidazol-2(3H)-one

HRID 1261397Notes

Reaction equation

HRID 1261397 reaction equation
C1N=CN([C:6](N2C=NC=C2)=[O:7])C=1.[F:13][C:14]1[C:19]2[CH:20]=[CH:21][O:22][C:18]=2[C:17]([NH2:23])=[C:16]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([I:31])=[CH:27][C:26]=2[F:32])[C:15]=1[F:33].O>C(Cl)Cl.C1COCC1>[F:33][C:15]1[C:16]2[N:24]([C:25]3[CH:30]=[CH:29][C:28]([I:31])=[CH:27][C:26]=3[F:32])[C:6](=[O:7])[NH:23][C:17]=2[C:18]2[O:22][CH:21]=[CH:20][C:19]=2[C:14]=1[F:13]

Participants

6

Reactant 3

HCID 962WaterHCID 682631,1'-CarbonyldiimidazoleHCID 683132694,5-Difluoro-N6-(2-fluoro-4-iodo-phenyl)-benzofuran-6,7-diamine2×

Product 1

HCID 672379484,5-Difluoro-3-(2-fluoro-4-iodophenyl)-1H-benzofuro[6,7-d]imidazol-2(3H)-oneYield 53.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

For scale up synthesis, CDI(92.4 g, 570 mmol) was added to a solution of 4,5-difluoro-N6-(2-fluoro-4-iodo-phenyl)-benzofuran-6,7-diamine (153.6 g, 380.1 mmol) in 1500 mL of DCM at 0° C. The solution was then warmed to room temperature and stirred for approximately 48 hours. Analysis showed 0.3% remaining of 4,5-difluoro-N6-(2-fluoro-4-iodo-phenyl)-benzofuran-6,7-diamine with 86.1% purity. The solution was filtered to give crude gray solid with 96.4% purity. The crude was dissolved in 1.5 L of THF and then water (1.5 L) was added. The suspension was then concentrated to 1.7 L and filtered to give 87 g of product with 98.0% purity (53.2% yield). 1H NMR (DMSO-d6, 400 MHz): δ 12.29 (bs, 1H), 8.09 (d, 1H), 7.94 (dd, 1H), 7.76 (d, 1H), 7.47 (t, 1H), 7.19 (d, 1H).

Workup

  1. filtrationThe solution was filtered
  2. customto give crude gray solid with 96.4% purity
  3. concentrationThe suspension was then concentrated to 1.7 L
  4. filtrationfiltered

Sources & evidence

ORD record
ord-21457e63ac7a423c95f7b77ec9940341
Source dataset
uspto-grants-2013_06
Patent number
US08470878B2

Reaction notes

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