Diisopropylethylamine → 3-[(4-Chlorophenyl)(3-{2-fluoro-1-[3-fluoro-5-(4H-1,2,4-triazol-4-yl)phenyl]-2-methylpropyl}azetidin-1-yl)methyl]benzonitrile

HRID 602717Notes

Reaction equation

HRID 602717 reaction equation
Cl.[NH:2]1[CH2:5][CH:4]([CH:6]([C:11]2[CH:12]=[C:13]([N:18]3[CH:22]=[N:21][N:20]=[CH:19]3)[CH:14]=[C:15]([F:17])[CH:16]=2)[C:7]([F:10])([CH3:9])[CH3:8])[CH2:3]1.Br[CH:24]([C:33]1[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][CH:34]=1)[C:25]1[CH:26]=[C:27]([CH:30]=[CH:31][CH:32]=1)[C:28]#[N:29].C(N(C(C)C)CC)(C)C>CC#N>[Cl:39][C:36]1[CH:35]=[CH:34][C:33]([CH:24]([N:2]2[CH2:3][CH:4]([CH:6]([C:11]3[CH:12]=[C:13]([N:18]4[CH:19]=[N:20][N:21]=[CH:22]4)[CH:14]=[C:15]([F:17])[CH:16]=3)[C:7]([F:10])([CH3:9])[CH3:8])[CH2:5]2)[C:25]2[CH:26]=[C:27]([CH:30]=[CH:31][CH:32]=2)[C:28]#[N:29])=[CH:38][CH:37]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 670553513-[Bromo(4-chlorophenyl)methyl]benzonitrileHCID 67065977HCID 67065977, compound

Product 1

HCID 114209993-[(4-Chlorophenyl)(3-{2-fluoro-1-[3-fluoro-5-(4H-1,2,4-triazol-4-yl)phenyl]-2-methylpropyl}azetidin-1-yl)methyl]benzonitrile

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A sample of 135 mg (0.41 mmole) of 4-[3-(1-Azetidin-3-yl-2-fluoro-2-methylpropyl)-5-fluorophenyl]-4H-1,2,4-triazole hydrochloride, 211 mg (0.62 mmole) of 3-[bromo(4-chlorophenyl)methyl]benzonitrile and 181 uL (1.025 mmole) of diisopropylethylamine in 5 mL of dry CH3CN was heated at reflux for 3 h. The solution was concentrated and the residue was dissolved in 20 mL of CH2Cl2 and 5 mL of NaHCO3. The layers were separated and the organic phase was dried over Na2SO4 and concentrated. The residue was purified on silica gel using CH2Cl2-EtOAc—NH3 (2M in MeOH), 200:50:4 to afford the title compound as a mixture of 4 diastereomers: Mass Spectrum: m/e=518 (M+1).

Workup

  1. temperatureat reflux for 3 h
  2. concentrationThe solution was concentrated
  3. dissolutionthe residue was dissolved in 20 mL of CH2Cl2
  4. customThe layers were separated
  5. dry with materialthe organic phase was dried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue was purified on silica gel

Sources & evidence

ORD record
ord-b8ccfe1049f24d7fa7c5d8e352dc3e26
Source dataset
uspto-grants-2011_03
Patent number
US07906503B2

Reaction notes

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