Potassium Phosphate, Tribasic → 4-(2-{2-[(2R)-2-methyl-1-pyrrolidinyl]ethyl}-6-quinolinyl)benzonitrile

HRID 860864Notes

Reaction equation

HRID 860864 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH2:12][CH2:13][N:14]1[CH2:18][CH2:17][CH2:16][C@H:15]1[CH3:19])[CH:6]=[CH:5]2.[C:20]([C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1)#[N:21].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C(O)(C)C.C(OCC)(=O)C>[CH3:19][C@@H:15]1[CH2:16][CH2:17][CH2:18][N:14]1[CH2:13][CH2:12][C:7]1[CH:6]=[CH:5][C:4]2[C:9](=[CH:10][CH:11]=[C:2]([C:25]3[CH:26]=[CH:27][C:22]([C:20]#[N:21])=[CH:23][CH:24]=3)[CH:3]=2)[N:8]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27343264-Cyanophenylboronic acidHCID 671046156-bromo-2-{2-[(2R)-2-methyl-1-pyrrolidinyl]ethyl}quinoline

Product 1

HCID 251970934-(2-{2-[(2R)-2-methyl-1-pyrrolidinyl]ethyl}-6-quinolinyl)benzonitrile

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

The product from Example 42D (160 mg, 0.5 mmol), 4-cyanophenylboronic acid (0.75 mmol), and dichlorobis(triphenylphosphine) palladium (II) (35.1 mg, 0.05 mmol) were combined in isopropyl alcohol (5.0 mL) and 0.2 M K3PO4 aq. solution (5.0 mL, 1.0 mmol) and heated at 60° C. for 24 hours. The reaction mixture was allowed to cool to room temperature and diluted with ethyl acetate (20 mL). The organic phase was separated, washed with 5% NaHCO3 (25 mL×3), 25% brine (25 mL), dried over Na2SO4, filtered, and the filtrate concentrated to dryness. The residue was purified by column chromatography (heptane:acetone:CH2Cl2:TEA (60:40:5:1) to provide the title compound. The title compound was treated with one equivalent of L-tartaric acid in IPA:ethanol to give the tartrate salt. mp 164° C.; MS (ESI) 342 (M+H)+; 1H NMR (DMSO-d6) δ 8.40 (1H, d), 8.38 (1H, d), 8.12 (1H, d), 8.06 (1H, d), 8.04 (2H, d), 7.98 (2H, d), 7.58 (1H, d), 4.05 (2H, s), 3.63 (1H, m), 3.50 (1H, m), 3.33 (2H, t), 3.15 (2H, m), 2.88 (1H, m), 2.09 (1H, m), 1.86 (2H, m), 1.55 (1H, m), 1.29 (3H, d).

Workup

  1. customThe organic phase was separated
  2. washwashed with 5% NaHCO3 (25 mL×3), 25% brine (25 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationthe filtrate concentrated to dryness
  6. customThe residue was purified by column chromatography (heptane:acetone:CH2Cl2:TEA (60:40:5:1)

Sources & evidence

ORD record
ord-97b4455b21f84da9b80c17cf915840df
Source dataset
uspto-grants-2006_12
Patent number
US07153889B2

Reaction notes

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