Toluene → 4-Chloro-7-isopropyl-5-(4-methoxyphenyl)pyrrolo[2,3-d]pyrimidine

HRID 611523Notes

Reaction equation

HRID 611523 reaction equation
[Cl:1][C:2]1[C:3]2[C:10](I)=[CH:9][N:8]([CH:12]([CH3:14])[CH3:13])[C:4]=2[N:5]=[CH:6][N:7]=1.[CH3:15][O:16][C:17]1[CH:22]=[CH:21][C:20](B(O)O)=[CH:19][CH:18]=1.C1(C)C=CC=CC=1.C(=O)(O)[O-].[Na+]>C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.O.C(O)C>[Cl:1][C:2]1[C:3]2[C:10]([C:20]3[CH:21]=[CH:22][C:17]([O:16][CH3:15])=[CH:18][CH:19]=3)=[CH:9][N:8]([CH:12]([CH3:14])[CH3:13])[C:4]=2[N:5]=[CH:6][N:7]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 201262(4-Methoxyphenyl)boronic acidHCID 516892Sodium BicarbonateHCID 195974264-Chloro-5-iodo-7-(propan-2-yl)-7H-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 195974834-Chloro-7-isopropyl-5-(4-methoxyphenyl)pyrrolo[2,3-d]pyrimidine

Reagents, catalysts & solvents 3

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
105 °C

Procedure

A mixture of 4-chloro-5-iodo-7-isopropylpyrrolo[2,3-d]pyrimidine (2.8 g), 4-methoxybenzeneboronic acid (1.32 g), bis(triphenylphosphine)palladium (II) chloride (625 mg), toluene (85 ml), ethanol (11 ml), water (22 ml) and sodium bicarbonate (2.2 g) was heated under nitrogen at 105° C. for 18 hours. The mixture was allowed to cool to ambient temperature and then partitioned between ethyl acetate (100 ml) and brine (100 ml). The organic layer was separated and the aqueous layer was washed with ethyl acetate (2×50 ml). The combined organic layers were washed with water, dried, filtered and evaporated under reduced pressure to give a black oil which solidified on cooling. This material was purified by flash column chromatography on silica using cyclohexane/ethyl acetate (7:3) as the mobile phase. Appropriate fractions were combined and concentrated under reduced pressure to give a yellow oil which solidified on standing to give 4-chloro-7-isopropyl-5-(4-methoxyphenyl)pyrrolo[2,3-d]pyrimidine. The structure was confirmed by 1H nmr.

Workup

  1. temperatureto cool to ambient temperature
  2. custompartitioned between ethyl acetate (100 ml) and brine (100 ml)
  3. customThe organic layer was separated
  4. washthe aqueous layer was washed with ethyl acetate (2×50 ml)
  5. washThe combined organic layers were washed with water
  6. customdried
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customto give a black oil which
  10. temperatureon cooling
  11. customThis material was purified by flash column chromatography on silica
  12. concentrationconcentrated under reduced pressure
  13. customto give a yellow oil which

Sources & evidence

ORD record
ord-a7e8083f944e4c6db1ff302eb385000e
Source dataset
uspto-grants-1999_12
Patent number
US06001839

Reaction notes

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