2,6-Dimethylphenol → HCID 56682223, compound

HRID 2039852Notes

Reaction equation

HRID 2039852 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[OH:9].[H-].[Na+].C(OC([N:19]1[CH2:24][CH2:23][N:22]([C:25]([C:27]2[C:35]3[C:30](=[N:31][CH:32]=[CH:33][C:34]=3[CH2:36][CH2:37][CH3:38])[N:29]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[C:28]=2Cl)=[O:26])[CH2:21][CH2:20]1)=O)(C)(C)C>CN1C(=O)CCC1>[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[O:9][C:28]1[N:29]([C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=2)[C:30]2=[N:31][CH:32]=[CH:33][C:34]([CH2:36][CH2:37][CH3:38])=[C:35]2[C:27]=1[C:25]([N:22]1[CH2:23][CH2:24][NH:19][CH2:20][CH2:21]1)=[O:26]

Participants

5

Reactant 3

HCID 113352,6-DimethylphenolHCID 24758Sodium hydrideHCID 66922206HCID 66922206, compound

Product 1

HCID 56682223HCID 56682223, compoundYield 35.1%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a solution of 2,6-dimethylphenol (152 mg, 1.24 mmol) in NMP (3 ml) was added sodium hydride (50 mg, 1.24 mmol, 60% dispersion in mineral oil), and the suspension was stirred at room temperature under an argon atmosphere for 20 min. After addition of 100 mg (207 μmol) of the compound of step 7, the reaction mixture was stirred for 2 h at 140° C. After cooling, the reaction mixture was quenched with water and extracted with EA. The organic phases were concentrated and the remaining residue was dissolved in DCM (12 ml) and TFA (3 ml) and stirred at room temperature for 2 h. The solvents were evaporated and the resulting solid was purified by preparative HPLC. The fractions containing the title compound were combined and lyophilized overnight. The obtained solid was dissolved in a small quantity of MOH, mixed with hydrochloric acid (0.1 M) and lyophilized overnight to give 34 mg of the title compound in the form of the [2-(2,6-dimethyl-phenoxy)-1-phenyl-4-propyl-1H-pyrrolo[2,3-b]pyridin-3-yl]-piperazin-1-yl-methanone dihydrochloride.

Workup

  1. stirringthe reaction mixture was stirred for 2 h at 140° C
  2. temperatureAfter cooling
  3. customthe reaction mixture was quenched with water
  4. extractionextracted with EA
  5. concentrationThe organic phases were concentrated
  6. dissolutionthe remaining residue was dissolved in DCM (12 ml)
  7. stirringTFA (3 ml) and stirred at room temperature for 2 h
  8. customThe solvents were evaporated
  9. customthe resulting solid was purified by preparative HPLC
  10. additionThe fractions containing the title compound
  11. waitlyophilized overnight
  12. dissolutionThe obtained solid was dissolved in a small quantity of MOH
  13. additionmixed with hydrochloric acid (0.1 M)
  14. waitlyophilized overnight

Sources & evidence

ORD record
ord-7af493cafa5e4ca99f6063400bd4258b
Source dataset
uspto-grants-2013_11
Patent number
US08580813B2

Reaction notes

Loading…