Hydrochloric Acid → 4-Amino-6-(4-chloro-2-fluoro-3-methoxyphenyl)-3-ethynyl-pyridine-2-carboxylic acid methyl ester

HRID 2386143Notes

Reaction equation

HRID 2386143 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:10]([C:11]#[C:12][Si](C)(C)C)=[C:9]([NH:17]C(=O)C)[CH:8]=[C:7]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([O:28][CH3:29])[C:22]=2[F:30])[N:6]=1)=[O:4].C(Cl)(=O)C.C(=O)([O-])[O-].[K+].[K+].Cl>CO>[CH3:1][O:2][C:3]([C:5]1[C:10]([C:11]#[CH:12])=[C:9]([NH2:17])[CH:8]=[C:7]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([O:28][CH3:29])[C:22]=2[F:30])[N:6]=1)=[O:4]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6367Acetyl chlorideHCID 11430Potassium CarbonateHCID 594321384-Acetylamino-6-(4-chloro-2-fluoro-3-methoxyphenyl)-3-trimethylsilanylethynylpyridine-2-carboxylic acid methyl ester

Product 1

HCID 594321094-Amino-6-(4-chloro-2-fluoro-3-methoxyphenyl)-3-ethynyl-pyridine-2-carboxylic acid methyl esterYield 74.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

4-Acetylamino-6-(4-chloro-2-fluoro-3-methoxyphenyl)-3-trimethylsilanylethynylpyridine-2-carboxylic acid methyl ester (0.196 g, 0.437 mmol) was suspended in methanol (4.36 mL) and acetyl chloride (0.310 mL, 4.37 mmol) was added. The reaction mixture was stirred overnight at ambient temperature then concentrated to dryness. The residue was dissolved in methanol (4.36 mL) and potassium carbonate (0.121 g, 0.873 mmol) was added. The reaction mixture was stirred at ambient temperature for 2 h, acidified with 2N HCl, and concentrated but not to dryness. The residue was partitioned between ethyl acetate and sodium bicarbonate; and the organic phase was dried and concentrated. The resulting product was purified by flash chromatography on silica gel (ethyl acetate/hexane gradient) to yield the title compound (0.109 g, 74.6% yield) as a yellow solid, mp 167-169° C.: 1H NMR (CDCl3) δ 7.7 (m, 1H), 7.24 (s, 1H), 7.18 (m, 1H), 5.08 (br s, 2H), 3.99 (s, 3H), 3.97 (d, 3H), 3.84 (s, 1H).

Workup

  1. concentrationthen concentrated to dryness
  2. dissolutionThe residue was dissolved in methanol (4.36 mL)
  3. stirringThe reaction mixture was stirred at ambient temperature for 2 h
  4. concentrationconcentrated but not to dryness
  5. customThe residue was partitioned between ethyl acetate and sodium bicarbonate
  6. customand the organic phase was dried
  7. concentrationconcentrated
  8. customThe resulting product was purified by flash chromatography on silica gel (ethyl acetate/hexane gradient)

Sources & evidence

ORD record
ord-286656e31df64f45bb143a66d0d9c93a
Source dataset
uspto-grants-2012_09
Patent number
US08268753B2

Reaction notes

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