Sodium Hydroxide → HCID 86672643, compound

HRID 1616358Notes

Reaction equation

HRID 1616358 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([C:12]2[CH:17]=[CH:16][C:15]([CH2:18][N:19]([CH3:21])[CH3:20])=[CH:14][CH:13]=2)[N:11]=1)[C:5]([O:7]C)=O.[OH-].[Na+].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[NH2:57][CH2:58][C:59]1[C:60](=[O:67])[NH:61][C:62]([CH3:66])=[CH:63][C:64]=1[CH3:65]>C(O)C.O.CS(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([C:12]2[CH:17]=[CH:16][C:15]([CH2:18][N:19]([CH3:21])[CH3:20])=[CH:14][CH:13]=2)[N:11]=1)[C:5]([NH:57][CH2:58][C:59]1[C:60](=[O:67])[NH:61][C:62]([CH3:66])=[CH:63][C:64]=1[CH3:65])=[O:7]

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 2724699PyBOPHCID 70638443-(Aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-oneHCID 86672642HCID 86672642, compound

Product 1

HCID 86672643HCID 86672643, compoundYield 44.7%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 702EthanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
60 °C

Procedure

To a solution of methyl 2-chloro-6-(4-((dimethylamino)methyl)phenyl)isonicotinate (0.48 g, 1.578 mmol) in ethanol (5 mL), NaOH (0.094 g, 2.368 mmol), dissolved in water (1 mL), was added and reaction mass heated at 60° C. for 1 h. On completion, solvent was evaporated under reduced pressure. Residue was washed with ether and acidified with 1N HCl till pH 8 and then with citric acid till pH 5-6. Aqueous layer was extracted with 20% MeOH/DCM and combined organic layers were concentrated under reduced pressure to afford the acid (0.47 g, crude) which was used in next step without further purification. To a solution of this acid (0.47 g, 1.64 mmol) in DMSO (4 mL), PyBOP (1.26 g, 2.43 mmol) was added and reaction stirred at rt for 15 min. Then 3-(aminomethyl)-4,6-dimethylpyridin-2(1H)-one (0.49 g, 3.28 mmol) was added and reaction stirred overnight. On completion, water was added and aqueous layer extracted with 20% MeOH/DCM. Combined organic layers were concentrated and residue purified by silica gel column chromatography affording 2-chloro-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-6-(4-((dimethylamino)methyl)phenyl)isonicotinamide (0.3 g, 43.6%)

Workup

  1. additionwas added
  2. customreaction mass
  3. customOn completion, solvent was evaporated under reduced pressure
  4. washResidue was washed with ether
  5. extractionAqueous layer was extracted with 20% MeOH/DCM
  6. concentrationwere concentrated under reduced pressure
  7. customto afford the acid (0.47 g, crude) which
  8. customwas used in next step without further purification
  9. customreaction
  10. customreaction
  11. stirringstirred overnight
  12. extractionaqueous layer extracted with 20% MeOH/DCM
  13. concentrationCombined organic layers were concentrated
  14. customresidue purified by silica gel column chromatography

Sources & evidence

ORD record
ord-2f1f838ae78d45f7b99b3fa13a3660cf
Source dataset
uspto-grants-2014_07
Patent number
US08765732B2

Reaction notes

Loading…