Ethyl orthoformate → HCID 21114190, compound

HRID 1925838Notes

Reaction equation

HRID 1925838 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.[CH:24](OCC)(OCC)OCC.CC1C=CC(S(O)(=O)=O)=CC=1.O>CCO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:10]([C:19]3[O:20][CH:24]=[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

5

Reactant 3

HCID 31214Ethyl orthoformateHCID 521998p-Toluenesulfonic acid monohydrateHCID 588906866-(4-Chloro-2-methyl-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid hydrazide

Product 1

HCID 21114190HCID 21114190, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

6-(4-Chloro-2-methyl-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid hydrazide 20b (0.048 g, 0.144 mmol) is suspended in 3 mL absolute EtOH and HC(OEt)3 (0.60 mL, 3.54 mmol) is added followed by catalytic pTsOH.H2O. The reaction mixture is heated to reflux under N2. After 2 hours, the reaction mixture is cooled to room temperature and concentrated under reduced pressure. Purification by flash column chromatography (97:3 ethyl acetate:MeOH) provides 36 mg (73%) desired product as a light yellow solid. LC/MS ESI (+) m/z 344, 346 (M+Cl pattern) detected; 1H NMR (400 MHz, DMSO-d6) δ13.10 (bs, 1H), 9.39 (s, 1H), 8.49 (s, 1H), 8.10 (bs, 1H), 7.78 (bs, 1H), 7.20 (d, 1H), 7.00 (dd, 1H), 6.41 (bs, 1H), 2.18 (s, 3H).

Workup

  1. temperatureThe reaction mixture is heated
  2. temperatureto reflux under N2
  3. concentrationconcentrated under reduced pressure
  4. customPurification by flash column chromatography (97:3 ethyl acetate:MeOH)

Sources & evidence

ORD record
ord-dfcf40e2d6104c158437a596d20cf2da
Source dataset
uspto-grants-2012_05
Patent number
US08178693B2

Reaction notes

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