Water → (2R)-N-Benzyl-2-{[5-(4-ethylphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]oxy}-N-methylpropane-1-amine

HRID 1926909Notes

Reaction equation

HRID 1926909 reaction equation
[H-].[Na+].[CH2:3]([N:10]([CH3:15])[CH2:11][C@H:12]([OH:14])[CH3:13])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl[C:17]1[C:18]2[C:25]([C:26]3[CH:31]=[CH:30][C:29]([CH2:32][CH3:33])=[CH:28][CH:27]=3)=[C:24]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[O:23][C:19]=2[N:20]=[CH:21][N:22]=1.O>C1COCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C>[CH2:3]([N:10]([CH3:15])[CH2:11][C@H:12]([O:14][C:17]1[C:18]2[C:25]([C:26]3[CH:27]=[CH:28][C:29]([CH2:32][CH3:33])=[CH:30][CH:31]=3)=[C:24]([C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=3)[O:23][C:19]=2[N:20]=[CH:21][N:22]=1)[CH3:13])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

8

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 15005725(2R)-1-[Benzyl(methyl)amino]propan-2-olHCID 580168974-Chloro-5-(4-ethylphenyl)-6-phenylfuro[2,3-d]pyrimidine

Product 1

HCID 58016821(2R)-N-Benzyl-2-{[5-(4-ethylphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]oxy}-N-methylpropane-1-amine

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Add 167 mg (4.18 mmol) sodium hydride (as 60% dispersion in mineral oil) to a solution of 600 mg (3.35 mmol) (2R)-1-[benzyl(methyl)amino]propan-2-ol in 7 ml THF at room temperature. After stirring for ten minutes, add a solution of 1177 mg (3.51 mmol) 4-chloro-5-(4-ethylphenyl)-6-phenylfuro[2,3-d]pyrimidine in 8 ml THF and 62 mg (0.17 mmol) tetra-n-butylammonium iodide. Stir the reaction mixture for 16 h under reflux. After adding water and ethyl acetate, wash the separated organic phase with 1 N hydrochloric acid and satd. sodium chloride solution. Re-extract the aqueous phase with ethyl acetate. Combine the organic phases and dry over sodium sulphate, and filter. Concentrate the filtrate by vacuum evaporation. Take up the residue in cyclohexane/ethyl acetate/dichloromethane and chromatograph on silica gel (solvent: cyclohexane/ethyl acetate 5:1, 2:1, 1:1, then ethyl acetate). 1366 mg (83% of theor.) of the desired product is obtained.

Workup

  1. stirringStir the reaction mixture for 16 h
  2. temperatureunder reflux
  3. washwash the separated organic phase with 1 N hydrochloric acid
  4. dry with materialdry over sodium sulphate
  5. filtrationfilter
  6. concentrationConcentrate the filtrate
  7. customby vacuum evaporation

Sources & evidence

ORD record
ord-a4dfc2ac02b84e179a362cc37d51c33d
Source dataset
uspto-grants-2012_05
Patent number
US08183246B2

Reaction notes

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