Dimethylformamide → HCID 9800722, compound

HRID 2300848Notes

Reaction equation

HRID 2300848 reaction equation
[C:1]1([C@@H:7]([NH:9][C:10]2[N:15]=[C:14](N3C4C=CC([Sn](CCCC)(CCCC)CCCC)=CC=4N=C3)[CH:13]=C[N:11]=2)[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[C:39]1[CH:40]=[N:41][CH:42]=[N:43][CH:44]=1.[CH3:45][N:46]([CH:48]=O)[CH3:47]>C1COCC1.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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>[C:1]1([C@@H:7]([NH:9][C:10]2[N:11]=[C:45]([N:46]3[C:47]4[CH:4]=[CH:3][C:2]([C:39]5[CH:40]=[N:41][CH:42]=[N:43][CH:44]=5)=[CH:1][C:7]=4[N:9]=[CH:48]3)[CH:13]=[CH:14][N:15]=2)[CH3:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

7

Reactant 3

HCID 6228DimethylformamideHCID 783445-BromopyrimidineHCID 69961490HCID 69961490, compound

Product 1

HCID 9800722HCID 9800722, compound

Reagents, catalysts & solvents 3

HCID 80271Tri-o-tolylphosphineCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of 2-[(S)-1-phenylethylamino]-4-[5-(tributylstannyl)-benzimidazol-1-yl]pyrimidine (27.7 mg) in THF (3 mL) was added 5-bromopyrimidine (22 mg), Pd2DBA3 (0.26 mg) and tri-o-tolylphosphine (0.47 mg). The mixture was heated and maintained at reflux for 2 h. Thin layer chromatographic analysis indicated there was mostly starting material present. DMF (3 mL) was added and the THF was removed under a stream of nitrogen. Tetrakis(triphenylphosphine)palladium(0) (1 mg) was added and the mixture was heated under nitrogen and maintained at 100° C. overnight. The mixture was then cooled and poured into 100 mL of 3:1 ether/ethyl acetate and washed 2× with water and then brine. The organic layer was dried over anhydrous Na2SO4, filtered and concentrated. The product was purified by silica gel chromatography eluting with methanol in dichloromethane to give 11.3 mg of the title compound. Mass spectrum (ESI): 394.2 (M+1).

Workup

  1. temperatureThe mixture was heated
  2. temperaturemaintained
  3. temperatureat reflux for 2 h
  4. customthe THF was removed under a stream of nitrogen
  5. additionTetrakis(triphenylphosphine)palladium(0) (1 mg) was added
  6. temperaturethe mixture was heated under nitrogen
  7. temperatureThe mixture was then cooled
  8. additionpoured into 100 mL of 3:1 ether/ethyl acetate
  9. washwashed 2× with water
  10. dry with materialThe organic layer was dried over anhydrous Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe product was purified by silica gel chromatography
  14. washeluting with methanol in dichloromethane

Sources & evidence

ORD record
ord-9562e4fc289a4cf28171bad84f814b80
Source dataset
uspto-grants-2002_12
Patent number
US06498165B1

Reaction notes

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