Diisopropylethylamine → 5-Bromo-2-((S)-3-fluoro-pyrrolidin-1-yl)-nicotinonitrile

HRID 55861Notes

Reaction equation

HRID 55861 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][C:5](Cl)=[C:6]([CH:9]=1)[C:7]#[N:8].Cl.[F:12][C@H:13]1[CH2:17][CH2:16][NH:15][CH2:14]1.CCN(C(C)C)C(C)C>CC#N>[Br:1][C:2]1[CH:3]=[N:4][C:5]([N:15]2[CH2:16][CH2:17][C@H:13]([F:12])[CH2:14]2)=[C:6]([CH:9]=1)[C:7]#[N:8]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 16217739(s)-3-Fluoropyrrolidine hydrochlorideHCID 219482695-Bromo-2-chloronicotinonitrile

Product 1

HCID 903566975-Bromo-2-((S)-3-fluoro-pyrrolidin-1-yl)-nicotinonitrile

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

5-Bromo-2-chloro-nicotinonitrile (6) (5.0 g, 23.0 mmol) was dissolved in MeCN (100 mL). (S)-3-Fluoropyrrolidine hydrochloride (5.7 g, 53.0 mmol) and DIPEA (12.0 mL, 68.9 mmol) were added and the mixture was stirred at reflux for 1 hour. The solvent was evaporated in vacuo and the residue partitioned between EtOAc (100 mL) and H2O (50 mL). The layers were separated and the organic phase washed with saturated brine solution (50 mL), then dried (MgSO4), filtered and the solvent evaporated in vacuo. The title compound was obtained as an off-white solid (6.2 g, 100%); LCMS, Rt=2.91 min (MeOH-FA method), m/z 270, 272 (MH+).

Workup

  1. temperatureat reflux for 1 hour
  2. customThe solvent was evaporated in vacuo
  3. customthe residue partitioned between EtOAc (100 mL) and H2O (50 mL)
  4. customThe layers were separated
  5. washthe organic phase washed with saturated brine solution (50 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customthe solvent evaporated in vacuo

Sources & evidence

ORD record
ord-959ad8dfe6724d83b24fbb5c45a759ae
Source dataset
uspto-grants-2016_09
Patent number
US09433622B2

Reaction notes

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