Sodium Carbonate → HCID 58938578, compound

HRID 598187Notes

Reaction equation

HRID 598187 reaction equation
[CH2:1]([N:4]([CH2:18][CH2:19][CH3:20])[C:5]1[N:6]([CH3:17])[C:7](=[O:16])[C:8]2[C:13](I)=[CH:12][N:11]([CH3:15])[C:9]=2[N:10]=1)[CH2:2][CH3:3].[Cl:21][C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[C:24]([CH3:31])[CH:23]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.C(O)C.O.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:21][C:22]1[CH:27]=[CH:26][C:25]([C:13]2[C:8]3[C:7](=[O:16])[N:6]([CH3:17])[C:5]([N:4]([CH2:18][CH2:19][CH3:20])[CH2:1][CH2:2][CH3:3])=[N:10][C:9]=3[N:11]([CH3:15])[CH:12]=2)=[C:24]([CH3:31])[CH:23]=1

Participants

9

Reactant 3

HCID 10340Sodium CarbonateHCID 5017600(4-Chloro-2-methylphenyl)boronic acidHCID 67267350HCID 67267350, compound

Product 1

HCID 58938578HCID 58938578, compoundYield 11%

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of 2-(dipropylamino)-5-iodo-3,7-dimethyl-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one (115 mg, 0.296 mmol), 4-chloro-2-methylphenylboronic acid (76 mg, 0.446 mmol), sodium carbonate (47 mg, 0.443 mmol) and tetrakis(triphenylphosphine)palladium (34 mg, 0.0294 mmol) in 1,2-dimethoxyethane (1.5 ml), ethanol (0.75 ml) and water (0.75 ml) was stirred at 80° C. for 4 hours. After cooling, the reaction mixture was diluted with water and ethyl acetate. The insoluble material was removed off by filtration. The filtrate was extracted with ethyl acetate (×2). The combined organic layer was washed with brine (×1), dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with a 10-18% hexane/ethyl acetate gradient mixture. The fractions containing the title compound were purified again by column chromatography eluting with 18% hexane/ethyl acetate using silica gel coated with amine. The desired fractions were concentrated in vacuo, and the resulting oil was crystallized from hexane and washed with pentane to give 12 mg (11%) of the title compound.

Workup

  1. temperatureAfter cooling
  2. customThe insoluble material was removed off by filtration
  3. extractionThe filtrate was extracted with ethyl acetate (×2)
  4. washThe combined organic layer was washed with brine (×1)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel column chromatography
  8. washeluting with a 10-18% hexane/ethyl acetate gradient mixture
  9. additionThe fractions containing the title compound
  10. customwere purified again by column chromatography
  11. washeluting with 18% hexane/ethyl acetate
  12. concentrationThe desired fractions were concentrated in vacuo
  13. customthe resulting oil was crystallized from hexane
  14. washwashed with pentane

Sources & evidence

ORD record
ord-ecfc5b8b8d0446758feea9ba96a1d0ab
Source dataset
uspto-grants-2011_03
Patent number
US07897607B2

Reaction notes

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