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

HRID 245295Notes

Reaction equation

HRID 245295 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-bf42631f87d54317954174ce5fb43589
Source dataset
uspto-grants-2014_02
Patent number
US08658791B2

Reaction notes

Loading…