Water → HCID 58431157, compound

HRID 1040437Notes

Reaction equation

HRID 1040437 reaction equation
[CH3:1][O:2][C:3]1[CH:27]=[CH:26][C:6]([CH2:7][N:8]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)[C:9]2[N:14]=[C:13]([C:15]#[N:16])[CH:12]=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.[CH3:28][CH2:29][Mg+].[Br-].O>C1COCC1.C(Cl)Cl>[NH2:16][C:15]1([C:13]2[N:14]=[C:9]([N:8]([CH2:17][C:18]3[CH:19]=[CH:20][C:21]([O:24][CH3:25])=[CH:22][CH:23]=3)[CH2:7][C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:27][CH:26]=3)[CH:10]=[CH:11][CH:12]=2)[CH2:29][CH2:28]1

Participants

6

Reactant 3

HCID 962WaterHCID 58431082HCID 58431082, compoundHCID 178461630HCID 178461630, compound3×

Product 1

HCID 58431157HCID 58431157, compoundYield 19.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6-[bis-(4-methoxy-benzyl)-amino]-pyridine-2-carbonitrile (1.83 g, 5.09 mmol) in anhydrous THF (64 mL) was added Ti(Oi-Pr)4 (1.79 mL, 6.11 mmol) in one portion followed by EtMgBr (3.0 M solution in THF, 4.07 mL, 12.2 mmol) slowly over 5 min. The reaction was stirred at room temperature overnight. Additional Ti(Oi-Pr)4 (0.5 mL, 1.7 mmol) and EtMgBr (1.2 mL, 3.60 mmol) were added and stirring was continued for 2 h. Additional Ti(Oi-Pr)4 (1.8 mL, 6.1 mmol) and EtMgBr (3 M, 4.1 mL, 12 mmol) were added and stirring was continued for 3 h. Water (12 mL) was added to the reaction mixture causing the formation of a precipitate. The mixture was filtered through a pad of diatomaceous earth and the filtrate was concentrated in vacuo to give an orange/red oil. The concentrate was re-dissolved in CH2Cl2, causing precipitation of a white solid. After filtration, the filtrate was concentrated in vacuo and purified via iterative flash chromatography on silica gel (1→10% MeOH/CH2Cl2) to give 381 mg of the title compound as a light orange viscous oil, m/z 391.08 [M+2]+.

Workup

  1. stirringstirring
  2. waitwas continued for 2 h
  3. stirringstirring
  4. waitwas continued for 3 h
  5. filtrationThe mixture was filtered through a pad of diatomaceous earth
  6. concentrationthe filtrate was concentrated in vacuo
  7. customto give an orange/red oil
  8. customprecipitation of a white solid
  9. filtrationAfter filtration
  10. concentrationthe filtrate was concentrated in vacuo
  11. custompurified via iterative flash chromatography on silica gel (1→10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-6e486c85bbea4ed3bef064a762967b85
Source dataset
uspto-grants-2013_10
Patent number
US08552205B2

Reaction notes

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