Hydrochloric Acid → (S)-1-(6-Fluoro-1-pyridin-3-yl-1H-benzoimidazol-2-yl)ethylamine

HRID 242917Notes

Reaction equation

HRID 242917 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C@@H:10]([NH:12]C(=O)C)[CH3:11])[N:7]([C:16]3[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=3)[C:6]=2[CH:22]=1.Cl>>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C@@H:10]([NH2:12])[CH3:11])[N:7]([C:16]3[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=3)[C:6]=2[CH:22]=1

Participants

3

Reactant 2

HCID 313Hydrochloric AcidHCID 68157467N-[(S)-1-(6-Fluoro-1-pyridin-3-yl-1H-benzoimidazol-2-yl)ethyl]acetamide

Product 1

HCID 68158079(S)-1-(6-Fluoro-1-pyridin-3-yl-1H-benzoimidazol-2-yl)ethylamineYield 75%

Conditions

Temperature
100 °C

Procedure

A mixture of N—[(S)-1-(6-fluoro-1-pyridin-3-yl-1H-benzoimidazol-2-yl)ethyl]acetamide (126 mg) and 6N HCl (2 mL) was heated at 100° C. in a sealed vial for 1 h. After cooling to RT, the crude reaction mixture was partitioned between EtOAc and a saturated aqueous solution of NaHCO3. The organic fraction was washed with water, followed by brine, dried (Na2SO4) and concentrated in vacuo to afford 10 mg of crude material as an orange oil. The aqueous phase was re-extracted with DCM (×3) and the combined organic fractions were washed with brine, dried (Na2SO4) and concentrated in vacuo to afford 71 mg of crude material as a colourless oil. The crude materials were combined to afford the title compound as a pale orange oil (81 mg, 75%). 1H NMR (CDCl3, 400 MHz): δ 8.82 (1H, d, J=5.43 Hz), 8.75 (1H, s), 7.83 (1H, d, J=8.06 Hz), 7.73 (1H, dd, J=8.85, 4.75 Hz), 7.61-7.56 (1H, m), 7.06 (1H, t, J=9.26 Hz), 6.77 (1H, d, J=8.49 Hz), 4.14-4.04 (1H, m), 1.50 (3H, d, J=6.65 Hz)

Workup

  1. temperatureAfter cooling to RT
  2. customthe crude reaction mixture
  3. customwas partitioned between EtOAc
  4. washThe organic fraction was washed with water
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customto afford 10 mg of crude material as an orange oil
  8. extractionThe aqueous phase was re-extracted with DCM (×3)
  9. washthe combined organic fractions were washed with brine
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated in vacuo
  12. customto afford 71 mg of crude material as a colourless oil

Sources & evidence

ORD record
ord-e74904d208a345b3a4e15610deb5cceb
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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