Hydrochloric Acid → HCID 11164856, compound

HRID 216595Notes

Reaction equation

HRID 216595 reaction equation
[CH:1]1([CH2:4][O:5][NH:6][C:7]([C:9]2[C:25]([NH:26][C:27]3[CH:32]=[CH:31][C:30]([C:33]#[N:34])=[CH:29][C:28]=3[CH3:35])=[C:24]([F:36])[C:12]3[N:13]=[C:14](COCC[Si](C)(C)C)[NH:15][C:11]=3[CH:10]=2)=[O:8])[CH2:3][CH2:2]1.Cl.[OH-].[Na+]>CCO>[CH:1]1([CH2:4][O:5][NH:6][C:7]([C:9]2[C:25]([NH:26][C:27]3[CH:32]=[CH:31][C:30]([C:33]#[N:34])=[CH:29][C:28]=3[CH3:35])=[C:24]([F:36])[C:12]3[N:13]=[CH:14][NH:15][C:11]=3[CH:10]=2)=[O:8])[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 313Hydrochloric Acid2×HCID 14798Sodium HydroxideHCID 86617120HCID 86617120, compound

Product 1

HCID 11164856HCID 11164856, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
50 °C

Procedure

To a slurry of a 1:1 mixture of N1:N3 isomers 6-(4-cyano-2-methyl-phenylamino)-7-fluoro-(2-trimethylsilanyl-ethoxymethyl)-benzoimidazole-5-carboxylic acid cyclopropylmethyoxy-amide 11zz (28 mg, 0.055 mmol) in 0.5 mL EtOH is added 0.5 mL 10% HCl. The reaction mixture is heated to 50° C. with stirring overnight (Whitten et al., J. Org. Chem., 1986, 51, 1891-1894). An additional 0.5 mL 10% HCl is added and the reaction mixture stirred at 70° C. overnight. The reaction mixture is cooled to room temperature and neutralized to pH ˜8 with 1.5 mL 1N NaOH. The reaction mixture is extracted with ethyl acetate, dried (MgSO4) and concentrated under reduced pressure to give 14 mg (60%) of 90% pure product as a mixture of rotatomers: MS APCI (+) m/z 380 (M+1) detected; MS APCI (−) m/z 378 (M−1) detected; 1H NMR (400 MHz, MeOH-d4) δ 8.41 (bs, 1H), 7.75 (m, 1H), 7.50 (s, 1H), 7.38 (d, 1H), 6.51 (m, 1H), 3.72 (d, 0.5H), 3.65 (d, 1.5H), 2.41 (s, 3H), 0.98 (1H, m), 0.58 (d, 1.5H), 0.40 (d, 0.5H), 0.25 (d, 1.5H), 0.19 (d, 0.5H).

Workup

  1. additionTo a slurry of a 1:1 mixture of N1
  2. stirringthe reaction mixture stirred at 70° C. overnight
  3. extractionThe reaction mixture is extracted with ethyl acetate
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-6f1f6bfa30ed4f8c9826e404c19c2daf
Source dataset
uspto-grants-2012_06
Patent number
US08193230B2

Reaction notes

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