Potassium Carbonate → 6-(4-Chloro-2-methyl-phenylamino)-7-fluoro-3-oxazol-5-ylmethyl-3H-benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amide

HRID 217031Notes

Reaction equation

HRID 217031 reaction equation
[CH:1]1([CH2:4][O:5][NH:6][C:7]([C:9]2[C:20]([NH:21][C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][C:23]=3[CH3:29])=[C:19]([F:30])[C:12]3[N:13]=[CH:14][N:15]([CH2:16][CH:17]=[O:18])[C:11]=3[CH:10]=2)=[O:8])[CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].[N+:37]([CH2:39]S(C1C=CC(C)=CC=1)(=O)=O)#[C-:38]>CO>[CH:1]1([CH2:4][O:5][NH:6][C:7]([C:9]2[C:20]([NH:21][C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][C:23]=3[CH3:29])=[C:19]([F:30])[C:12]3[N:13]=[CH:14][N:15]([CH2:16][C:17]4[O:18][CH:39]=[N:37][CH:38]=4)[C:11]=3[CH:10]=2)=[O:8])[CH2:2][CH2:3]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 161915Tosylmethyl isocyanideHCID 865905256-(4-Chloro-2-methyl-phenylamino)-7-fluoro-3-(2-oxo-ethyl)-3H-benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amide

Product 1

HCID 113748106-(4-Chloro-2-methyl-phenylamino)-7-fluoro-3-oxazol-5-ylmethyl-3H-benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amideYield 50.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

6-(4-Chloro-2-methyl-phenylamino)-7-fluoro-3-(2-oxo-ethyl)-3H-benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amide (0.020 g, 0.046 mmol) is dissolved in methanol (2 mL). Potassium carbonate (0.013 g, 0.093 mmol) and 1-isocyanomethanesulfonyl-4-methyl-benzene (0.010 g, 0.051 mmol) are added. The reaction mixture is stirred at reflux for 16 hours under N2, then concentrated under reduced pressure. The residue is dissolved in ethyl acetate and poured into a reparatory funnel and washed with water and brine. The combined aqueous layers are reextracted with ethyl acetate (2×). The combined ethyl acetate layers are dried (Na2SO4) and concentrated under reduced pressure. The resulting solid was purified by flash column chromatography (eluting with 15:1 methylene chloride:methanol) to yield 0.011 g (50%) of the desired product. MS APCI (+) m/z 470, 472 (M+, Cl pattern) detected; 1H NMR (400 MHz, CDCl3) δ 10.51 (br s, 1H), 8.07 (s, 1H), 8.02 (s, 1H), 7.89 (s, 1H), 7.23 (s, 1H), 7.15 (d, 1H), 6.92 (dd, 1H), 6.31 (d, 1H), 6.11 (br s, 1H), 5.45 (s, 2H), 3.62 (d, 2H), 2.40 (s, 3H), 0.87 (m, 1H), 0.49 (m, 2H), 0.20 (m, 2H). 19F NMR (376 MHz, CDCl3) −134.54 (s).

Workup

  1. temperatureat reflux for 16 hours under N2
  2. concentrationconcentrated under reduced pressure
  3. dissolutionThe residue is dissolved in ethyl acetate
  4. additionpoured into a reparatory funnel
  5. washwashed with water and brine
  6. dry with materialThe combined ethyl acetate layers are dried (Na2SO4)
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting solid was purified by flash column chromatography (eluting with 15:1 methylene chloride:methanol)

Sources & evidence

ORD record
ord-8a5e2b1788414d189b797506b23a58df
Source dataset
uspto-grants-2012_06
Patent number
US08193231B2

Reaction notes

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