Phosgene → HCID 178426106, compound

HRID 1925837Notes

Reaction equation

HRID 1925837 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:10]([C:19]([NH:21][NH2:22])=[O:20])=[CH:11][C:12]3[NH:16][CH:15]=[N:14][C:13]=3[C:17]=2[F:18])=[C:4]([CH3:23])[CH:3]=1.[C:24](Cl)(Cl)=[O:25]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:10]([C:19]3[O:20][C:24]([OH:25])=[N:22][N:21]=3)=[CH:11][C:12]3[NH:16][CH:15]=[N:14][C:13]=3[C:17]=2[F:18])=[C:4]([CH3:23])[CH:3]=1

Participants

4

Reactant 2

HCID 6371PhosgeneHCID 588906866-(4-Chloro-2-methyl-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid hydrazide

Product 1

HCID 178426106HCID 178426106, compoundYield 99%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

6-(4-Chloro-2-methyl-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid hydrazide 20b (0.050 g, 0.150 mmol) is suspended in PhMe (2 mL) and a 20% phosgene solution in PhMe (0.24 mL, 0.45 mmol) is added. The reaction mixture is stirred at reflux under N2 for 1 hour and then cooled to room temperature. The reaction mixture is quenched by the addition of a 1:1 mixture of THF and 10% HCl (20 mL). The layers are separated and the aqueous layer is extracted with THF (3×). The combined organic layer is washed with brine, dried (Na2SO4) and concentrated under reduced pressure to give 54 mg (99%) of desired product as a yellow solid: LC/MS ESI (+) m/z 360, 362 (M+Cl pattern) detected; 1H NMR (400 MHz, DMSO-d6) δ 12.64 (s, 1H), 8.83 (s, 1H), 7.88 (s, 1H), 7.30 (s, 1H), 7.20 (d, 1H), 7.00 (dd, 1H), 6.38 (dd, 1H), 2.30 (s, 3H).

Workup

  1. temperatureat reflux under N2 for 1 hour
  2. customThe reaction mixture is quenched by the addition of a 1:1 mixture of THF and 10% HCl (20 mL)
  3. customThe layers are separated
  4. extractionthe aqueous layer is extracted with THF (3×)
  5. washThe combined organic layer is washed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-139a988b8a8b4d58b8c4b8317a9b9b65
Source dataset
uspto-grants-2012_05
Patent number
US08178693B2

Reaction notes

Loading…