Hydrochloric Acid → (5-Bromo-pyridin-2-yl)-(6-trifluoromethyl-pyridin-3-yl)-amine

HRID 1404235Notes

Reaction equation

HRID 1404235 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([F:11])([F:10])[F:9])=[N:6][CH:7]=1.[Br:12][C:13]1[CH:14]=[CH:15][C:16](F)=[N:17][CH:18]=1.Cl>C(O)CCC>[Br:12][C:13]1[CH:14]=[CH:15][C:16]([NH:1][C:2]2[CH:7]=[N:6][C:5]([C:8]([F:11])([F:9])[F:10])=[CH:4][CH:3]=2)=[N:17][CH:18]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 27377445-Amino-2-(trifluoromethyl)pyridineHCID 27831685-Bromo-2-fluoropyridine

Product 1

HCID 66615754(5-Bromo-pyridin-2-yl)-(6-trifluoromethyl-pyridin-3-yl)-amine

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 5-amino-2-(trifluoromethyl)pyridine (0.5 g, 3.0 mmol, 1.0 equiv) and 5-bromo-2-fluoropyridine (0.47 mL, 4.6 mmol, 1.5 equiv) in 2 mL 1-butanol was charged with 0.15 mL of 4.0 M HCl (in dioxane) and heated to 150° C. via microwave heating. After cooling to room temperature, the reaction mixture was partitioned between ethyl acetate and saturated bicarbonate, and the organic extracts were washed with brine and dried over sodium sulphate. Purification of the crude product by flash chromatography afforded the title compound: 1H NMR (400 MHz, CDCl3) δ 6.63 (br. s., 1 H) 6.67 (d, J=9.35 Hz, 1 H) 7.56 (d, J=8.59 Hz, 1 H) 7.62 (dd, J=8.84, 2.53 Hz, 1 H) 8.22-8.66 (m, 2 H) 8.57 (d, J=2.78 Hz, 1 H); (M+H)+ 320.0.

Workup

  1. temperatureheating
  2. temperatureAfter cooling to room temperature
  3. customthe reaction mixture was partitioned between ethyl acetate and saturated bicarbonate
  4. washthe organic extracts were washed with brine
  5. dry with materialdried over sodium sulphate
  6. customPurification of the crude product by flash chromatography

Sources & evidence

ORD record
ord-27efc71cf9af4db888bce4b80eaa02b6
Source dataset
uspto-grants-2014_12
Patent number
US08912208B2

Reaction notes

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