Hydrochloric Acid → 4-(5-Hydroxy-2-methylanilino)-2-(3-pyridinyl)-6-(trifluoromethyl)pyrimidine

HRID 1765216Notes

Reaction equation

HRID 1765216 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)[N:3]=1.[OH:18][C:19]1[CH:20]=[CH:21][C:22]([CH3:26])=[C:23]([CH:25]=1)[NH2:24].Cl.[OH-].[Na+]>O.C(O)C>[OH:18][C:19]1[CH:20]=[CH:21][C:22]([CH3:26])=[C:23]([CH:25]=1)[NH:24][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)[N:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 178203-Amino-p-cresolHCID 14859904-Chloro-2-(pyridin-3-yl)-6-(trifluoromethyl)pyrimidine

Product 1

HCID 227323484-(5-Hydroxy-2-methylanilino)-2-(3-pyridinyl)-6-(trifluoromethyl)pyrimidineYield 27%

Reagents, catalysts & solvents 1

HCID 19096565Water ethanolSolvent

Procedure

A mixture of 4-chloro-2-(3-pyridinyl)-6-(trifluoromethyl)pyrimidine (50 mg, 0.193 mmol), 5-hydroxy-2-methylaniline (36 mg, 0.290 mmol) and 2N HCl (150 μl) in water:ethanol (2:1, 10 ml) was refluxed for 24 h. The mixture was cooled to room temperature and neutralized with aqueous 2N NaOH to pH 6–7. The mixture was extracted with ethyl acetate (75 ml), washed with water (2×20 ml), aqueous saturated NaCl (1×20 ml) and dried over anhydrous sodium sulfate. The ethyl acetate solution was rotary evaporated to dryness and the residue was purified by column chromatography to give a yellow solid (18 mg, 27%). 1H NMR (Acetone-d6): 9.53–9.51 (m, 1H), 8.85 (s, 1H), 8.71 (dd, J=1.8, 4.8 Hz, 1H), 8.67–8.63 (m, 1H), 8.49 (s, 1H), 7.53–7.48 (m, 1H), 7.24 (s, 1H), 7.17 (d, J=8.1 Hz, 1H), 6.98 (s, 1H), 6.75 (dd, J=2.4, 8.4 Hz, 1H), 2.23 (s, 3H).

Workup

  1. temperaturewas refluxed for 24 h
  2. extractionThe mixture was extracted with ethyl acetate (75 ml)
  3. washwashed with water (2×20 ml), aqueous saturated NaCl (1×20 ml)
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe ethyl acetate solution was rotary evaporated to dryness
  6. customthe residue was purified by column chromatography

Sources & evidence

ORD record
ord-dfb27d93583c49e48c725cf18042bea5
Source dataset
uspto-grants-2007_06
Patent number
US07226927B2

Reaction notes

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