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

HRID 1176881Notes

Reaction equation

HRID 1176881 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 separatory funnel and washed with water and brine. The combined aqueous layers reextracted with ethyl acetate (2×). The combined ethyl acetate layer are dried (Na2SO4), and concentrated under reduced pressure. The resulting solid was purified by flash column chromatograhy (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, 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 separatory funnel
  5. washwashed with water and brine
  6. dry with materialThe combined ethyl acetate layer are dried (Na2SO4)
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting solid was purified by flash column chromatograhy (eluting with 15:1 methylene chloride:methanol)

Sources & evidence

ORD record
ord-868d4b688f5543218a41c5b308d48a26
Source dataset
uspto-grants-2010_11
Patent number
US07842816B2

Reaction notes

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