Triethylamine → 3-Amino-5,6-bis-trifluoromethyl-pyridine-2-carboxylic acid (3,3,3-trifluoro-2-hydroxy-2-methyl-propyl)-amide

HRID 444910Notes

Reaction equation

HRID 444910 reaction equation
[F:1][C:2]([F:32])([F:31])[C:3]([OH:30])([CH3:29])[CH2:4][NH:5][C:6]([C:8]1[C:13]([N:14]2C(C)=CC=C2C)=[CH:12][C:11]([C:21]([F:24])([F:23])[F:22])=[C:10]([C:25]([F:28])([F:27])[F:26])[N:9]=1)=[O:7].Cl.NO.CCN(CC)CC>CCO.O>[F:32][C:2]([F:1])([F:31])[C:3]([OH:30])([CH3:29])[CH2:4][NH:5][C:6]([C:8]1[C:13]([NH2:14])=[CH:12][C:11]([C:21]([F:24])([F:23])[F:22])=[C:10]([C:25]([F:27])([F:26])[F:28])[N:9]=1)=[O:7]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 443297Hydroxyamine hydrochlorideHCID 866576663-(2,5-Dimethyl-pyrrol-1-yl)-5,6-bis-trifluoromethyl-pyridine-2-carboxylic acid (3,3,3-trifluoro-2-hydroxy-2-methyl-propyl)-amide

Product 1

HCID 760260443-Amino-5,6-bis-trifluoromethyl-pyridine-2-carboxylic acid (3,3,3-trifluoro-2-hydroxy-2-methyl-propyl)-amide

Reagents, catalysts & solvents 1

HCID 19096565Water ethanolSolvent

Conditions

Temperature
98 °C

Procedure

To a stirred solution of 3-(2,5-dimethyl-pyrrol-1-yl)-5,6-bis-trifluoromethyl-pyridine-2-carboxylic acid (3,3,3-trifluoro-2-hydroxy-2-methyl-propyl)-amide (985 mg, 2.064 mmol) in 2:1 EtOH/H2O (7.5 ml) was added hydroxylamine hydrochloride (1.43 g, 20.64 mmol) followed by NEt3 (575 ml, 4.13 mmol). The reaction mixture was heated to reflux (˜98° C.) for 11.5 hours and then allowed to cool to RT. The solvent was removed in vacuo and the resulting residue was partitioned between EtOAc (25 ml) and water (25 ml). The aqueous layer was separated and extracted with EtOAc (2×25 ml) and the combined organic extracts were washed with brine (50 ml), dried (MgSO4) and concentrated in vacuo. The crude material was purified by chromatography on silica eluting with 0-25% EtOAc in iso-hexane to afford the title product as a pale yellow solid; LC-MS: Rt 1.24 min; MS m/z 400.0 [M+H]+; Method 2 minLC_v003.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto cool to RT
  3. customThe solvent was removed in vacuo
  4. customthe resulting residue was partitioned between EtOAc (25 ml) and water (25 ml)
  5. customThe aqueous layer was separated
  6. extractionextracted with EtOAc (2×25 ml)
  7. washthe combined organic extracts were washed with brine (50 ml)
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. customThe crude material was purified by chromatography on silica eluting with 0-25% EtOAc in iso-hexane

Sources & evidence

ORD record
ord-a64d49ff0395451fb01fbf6f68cc181b
Source dataset
uspto-grants-2013_07
Patent number
US08476269B2

Reaction notes

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