Potassium Carbonate → 4'-((1S,2R)-2-{2-[(2R)-2-Methylpyrrolidin-1-yl]ethyl}cyclopropyl)-1,1'-biphenyl-4-carbonitrile

HRID 73302Notes

Reaction equation

HRID 73302 reaction equation
CS(O[CH2:6][CH2:7][C@H:8]1[CH2:10][C@@H:9]1[C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:22]=[CH:21][C:20]([C:23]#[N:24])=[CH:19][CH:18]=2)=[CH:13][CH:12]=1)(=O)=O.C(=O)([O-])[O-].[K+].[K+].Br.[CH3:32][C@@H:33]1[CH2:37][CH2:36][CH2:35][NH:34]1>CN(C=O)C>[CH3:32][C@@H:33]1[CH2:37][CH2:36][CH2:35][N:34]1[CH2:6][CH2:7][C@H:8]1[CH2:10][C@@H:9]1[C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:22]=[CH:21][C:20]([C:23]#[N:24])=[CH:19][CH:18]=2)=[CH:13][CH:12]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 12444175(2R)-2-methylpyrrolidine hydrobromideHCID 86618016Methanesulfonic acid, 2-[(1R,2S)-2-(4'-cyano-biphenyl-4-yl)-cyclopropyl]-ethyl ester

Product 1

HCID 441973214'-((1S,2R)-2-{2-[(2R)-2-Methylpyrrolidin-1-yl]ethyl}cyclopropyl)-1,1'-biphenyl-4-carbonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of the mesylate from Example 28G (methanesulfonic acid, 2-[(1R,2S)-2-(4′-cyano-biphenyl-4-yl)-cyclopropyl]-ethyl ester) and potassium carbonate in DMF was added (R)-2-methylpyrrolidine hydrobromide [CAS 117607-13-3]. The mixture was stirred at 50° C. overnight. The mixture was partitioned between ethyl acetate and H2O. The organic layer was washed with brine, dried (MgSO4), and concentrated in vacuo. The resulting residue was purified by chromatography on silica gel eluted with 7.5/20/70 MeOH/EtOAc/CH2Cl2 to provide the title compound. 1H NMR (300 MHz, CDCl3, free base): δ 0.88-1.0 (m, 2H), 1.18 (d, J=6 Hz, 3H), 1.4-2.4 (m, 11H), 2.9 (m, 1H), 3.15-3.23 (m, 1H), 7.15 (d, J=9 Hz, 2H), 7.47 (d, J=9 Hz, 2H), 7.66 (q, J=9 Hz, 4H). MS (DCl—NH3) m/z 331.2 (M+H)+. Anal, Calc. for C23H26N2.C4H6O6 1.25H2O (L-tartaric acid salt): C, 64.46; H, 6.91; N, 5.57. Found: C, 64.46; H, 6.91; N, 5.57.

Workup

  1. customThe mixture was partitioned between ethyl acetate and H2O
  2. washThe organic layer was washed with brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue was purified by chromatography on silica gel
  6. washeluted with 7.5/20/70 MeOH/EtOAc/CH2Cl2

Sources & evidence

ORD record
ord-e06bebeadef34305900d87f9fa3183b5
Source dataset
uspto-grants-2014_09
Patent number
US08829041B2

Reaction notes

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