Sodium Carbonate → 1,1-Dimethylethyl (2S)-4-({4-[{[6-(3-fluorophenyl)-2-pyridinyl]carbonyl}(methyl)amino]phenyl}methyl)-2-methyl-1-piperazinecarboxylate

HRID 644763Notes

Reaction equation

HRID 644763 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]([N:10]([CH3:32])[C:11]2[CH:16]=[CH:15][C:14]([CH2:17][N:18]3[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C@@H:20]([CH3:31])[CH2:19]3)=[CH:13][CH:12]=2)=[O:9])[CH:5]=[CH:4][CH:3]=1.[F:33][C:34]1[CH:35]=[C:36](B(O)O)[CH:37]=[CH:38][CH:39]=1.C(=O)([O-])[O-].[Na+].[Na+].COCCOC.O>C(Cl)Cl.O>[F:33][C:34]1[CH:39]=[C:38]([C:2]2[N:7]=[C:6]([C:8]([N:10]([CH3:32])[C:11]3[CH:12]=[CH:13][C:14]([CH2:17][N:18]4[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:28])([CH3:30])[CH3:29])=[O:25])[C@@H:20]([CH3:31])[CH2:19]4)=[CH:15][CH:16]=3)=[O:9])[CH:5]=[CH:4][CH:3]=2)[CH:37]=[CH:36][CH:35]=1

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 27339863-Fluorophenylboronic acidHCID 18180031Water 1,2-dimethoxyethaneHCID 59262188HCID 59262188, compound

Product 1

HCID 592621831,1-Dimethylethyl (2S)-4-({4-[{[6-(3-fluorophenyl)-2-pyridinyl]carbonyl}(methyl)amino]phenyl}methyl)-2-methyl-1-piperazinecarboxylateYield 84.1%

Reagents, catalysts & solvents 1

HCID 21908982Water methylene chlorideSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 1,1-dimethylethyl (2S)-4-({4-[[(6-chloro-2-pyridinyl)carbonyl](methyl)amino]phenyl}methyl)-2-methyl-1-piperazinecarboxylate (D107) (0.0825 g, 0.179 mmol), 3-fluorobenzeneboronic acid (0.0302 g, 0.216 mmol), tetrakis-(triphenylphosphine)palladium (0) (0.0104 g, 0.009 mmol) and sodium carbonate (0.0762 g, 0.719 mmol) in a DME/water (4 mL, 1:1) was heated at 140° C. in a microwave for 10 minutes. The reaction mixture was diluted with DCM/water and the aqueous layer was further extracted with DCM (×3). The combined organics were dried and concentrated to give the crude product which was purified by column chromatography. Elution with 0-100% EtOAc/hexane gave the title compound as a colourless oil (0.0781 g). MS (ES): MH+ 519.3.

Workup

  1. extractionthe aqueous layer was further extracted with DCM (×3)
  2. customThe combined organics were dried
  3. concentrationconcentrated
  4. customto give the crude product which
  5. customwas purified by column chromatography
  6. washElution with 0-100% EtOAc/hexane

Sources & evidence

ORD record
ord-94d8ba7085e345d3906aba1d7fa124dd
Source dataset
uspto-grants-2010_04
Patent number
US07700599B2

Reaction notes

Loading…