N,N-Dimethylaniline → 2-(4-bromo-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-5-chlorobenzonitrile

HRID 657727Notes

Reaction equation

HRID 657727 reaction equation
P(Br)(Br)([Br:3])=O.[Cl:6][C:7]1[CH:8]=[CH:9][C:10]([N:15]2[CH2:25][CH2:24][C:18]3[N:19]=[CH:20][N:21]=[C:22](O)[C:17]=3[CH2:16]2)=[C:11]([CH:14]=1)[C:12]#[N:13].CN(C)C1C=CC=CC=1.[OH-].[K+]>C(#N)C.C1(OC)C=CC=CC=1.C(Cl)(Cl)Cl.CN(C)C=O>[Br:3][C:22]1[C:17]2[CH2:16][N:15]([C:10]3[CH:9]=[CH:8][C:7]([Cl:6])=[CH:14][C:11]=3[C:12]#[N:13])[CH2:25][CH2:24][C:18]=2[N:19]=[CH:20][N:21]=1

Participants

9

Reactant 4

HCID 949N,N-DimethylanilineHCID 14797Potassium HydroxideHCID 24613Phosphorus oxybromideHCID 178509898HCID 178509898, compound

Product 1

HCID 598406952-(4-bromo-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-5-chlorobenzonitrileYield 35.8%

Reagents, catalysts & solvents 4

HCID 6212ChloroformSolvent2×HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 7519AnisoleSolvent

Procedure

POBr3 (1.61 g, 5.6 mmol) was added portionwise over 2 min to a mixture of 5-chloro-2-(4-hydroxy-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)benzonitrile (0.82 g, 2.8 mmol), N,N-dimethylaniline (0.7 mL), and N,N-dimethylformamide (0.02 mL) in acetonitrile (10 mL) and anisole (10 mL). The mixture was heated under reflux for 2.5 h and LC-MS showed reaction was complete. After cooling the mixture was diluted with chloroform (20 mL) and poured into a stirred mixture of ice (50 g), 50% KOH (8 mL) and chloroform (100 mL). The organic layer was separated and the aqueous layer was extracted with chloroform (25 mL×2). The combined organic layers were washed with brine (100 mL), dred (Na2SO4), filtered and concentrated. The residue was purified by silica gel column to yield a brown solid (0.35 g).

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux for 2.5 h
  3. customreaction
  4. temperatureAfter cooling the mixture
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted with chloroform (25 mL×2)
  7. washThe combined organic layers were washed with brine (100 mL)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by silica gel column

Sources & evidence

ORD record
ord-d926e60f67434e2fa912f7eaffaaeba9
Source dataset
uspto-grants-2011_12
Patent number
US08076345B2

Reaction notes

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