N-methyl-2-pyrrolidone → HCID 68828575, compound

HRID 1986419Notes

Reaction equation

HRID 1986419 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH2:12][CH:13]([CH3:15])[CH3:14])[C:6]([CH2:16][NH2:17])=[C:5]2[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[CH3:24][N:25]1CCCC1=O>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:17][CH2:16][C:6]1[C:7]([CH2:12][CH:13]([CH3:15])[CH3:14])=[N:8][C:9]2[C:4]([C:5]=1[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[CH:3][C:2]([C:24]#[N:25])=[CH:11][CH:10]=2

Participants

5

Reactant 2

HCID 13387N-methyl-2-pyrrolidoneHCID 68832119HCID 68832119, compound

Product 1

HCID 68828575HCID 68828575, compoundYield 19%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
80 °C

Procedure

A solution of (6-bromo-2-isobutyl-4-phenylquinolin-3-yl)methylamine (0.20 g, 0.54 mmol) in N-methylpyrrolidone (8 ml) was stirred under a nitrogen atmosphere at 80° C. for 15 min. To the reaction mixture were added zinc cyanide (0.038 g, 0.32 mmol) and tetrakis(triphenylphosphine)palladium (0.032 g, 0.027 mmol), and the mixture was further stirred under a nitrogen atmosphere at 80° C. for 1 hr. The reaction mixture was partitioned between ethyl acetate (50 ml) and 28% aqueous ammonia (6 ml)-saturated aqueous ammonium chloride solution (22 ml)-water (22 ml). The organic layer was washed twice with 28% aqueous ammonia (6 ml)-saturated aqueous ammonium chloride solution (22 ml)-water (22 ml) and then with saturated brine (20 ml), and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by preparative HPLC and the objective fractions were combined and concentrated under reduced pressure. The residue was alkalified with saturated aqueous sodium hydrogen carbonate (50 ml) and extracted twice with ethyl acetate (50 ml). The organic layers were combined, washed with saturated brine (20 ml) and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was crystallized from n-hexane-ethyl acetate to give the title compound (0.032 g, yield 19%) as colorless crystals.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate (50 ml) and 28% aqueous ammonia (6 ml)-saturated aqueous ammonium chloride solution (22 ml)-water (22 ml)
  2. washThe organic layer was washed twice with 28% aqueous ammonia (6 ml)-saturated aqueous ammonium chloride solution (22 ml)-water (22 ml)
  3. dry with materialwith saturated brine (20 ml), and dried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated
  5. customthe residue was purified by preparative HPLC
  6. concentrationconcentrated under reduced pressure
  7. extractionextracted twice with ethyl acetate (50 ml)
  8. washwashed with saturated brine (20 ml)
  9. dry with materialdried over anhydrous magnesium sulfate
  10. customThe solvent was evaporated
  11. customthe residue was crystallized from n-hexane-ethyl acetate

Sources & evidence

ORD record
ord-45e4d6f989a14185bfaa5cb1b9bc70c1
Source dataset
uspto-grants-2009_06
Patent number
US07547710B2

Reaction notes

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