1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → 2-(4-methoxy-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-5-methylbenzonitrile

HRID 657728Notes

Reaction equation

HRID 657728 reaction equation
[CH3:1][O:2][C:3]1[C:4]2[CH2:12][NH:11][CH2:10][CH2:9][C:5]=2[N:6]=[CH:7][N:8]=1.Br[C:14]1[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][C:15]=1[C:16]#[N:17].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CC(C)([O-])C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[CH3:1][O:2][C:3]1[C:4]2[CH2:12][N:11]([C:14]3[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][C:15]=3[C:16]#[N:17])[CH2:10][CH2:9][C:5]=2[N:6]=[CH:7][N:8]=1

Participants

6

Reactant 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 125572012-Bromo-5-methylbenzonitrileHCID 23676156Sodium t-butoxideHCID 509892144-methoxy-5H,6H,7H,8H-pyrido[4,3-d]pyrimidine

Product 1

HCID 598407122-(4-methoxy-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-5-methylbenzonitrile

Reagents, catalysts & solvents 1

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalyst

Procedure

A 100 mL flask was charged with 4-methoxy-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (2.78 g, 16 mmol), 2-bromo-5-methylbenzonitrile (4.18 g, 19.2 mmol), bis(dibenzylideneacetone)palladium(0) (372 mg, 0.64 mmol), xantphos (529 mg, 0.896 mmol), and sodium tert-butoxide (2.33 g, 24 mmol), capped with a septum and purged with nitrogen. Dry argon-sparged toluene (50 mL) was added. The heterogeneous mixture was placed in an oil bath at 100° C., and heated under argon overnight. After 14 hours, TLC showed the reaction was complete. The mixture was removed from the heat, diluted with ethyl acetate (50 mL), filtered and concentrated in vacuo. The residue was purified by silica gel column (0-100% EtOAc/hexane) to afford a light orange solid.

Workup

  1. customcapped with a septum
  2. custompurged with nitrogen
  3. customDry argon-sparged toluene (50 mL)
  4. additionwas added
  5. customThe heterogeneous mixture was placed in an oil bath at 100° C.
  6. temperatureheated under argon overnight
  7. customThe mixture was removed from the heat
  8. additiondiluted with ethyl acetate (50 mL)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by silica gel column (0-100% EtOAc/hexane)
  12. customto afford a light orange solid

Sources & evidence

ORD record
ord-21cd55d605a647a0bbd887eacb573e8f
Source dataset
uspto-grants-2011_12
Patent number
US08076345B2

Reaction notes

Loading…