1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → HCID 86670120, compound

HRID 2169573Notes

Reaction equation

HRID 2169573 reaction equation
Br[C:2]1[C:3]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH:10]2[C:15]([NH:17][C@H:18]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH3:19])=[O:16])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:8][C:5]1[N:6]=[CH:7][C:2]2[N:17]([CH:18]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH3:19])[C:15](=[O:16])[C@@H:10]3[CH2:11][O:12][CH2:13][CH2:14][N:9]3[C:3]=2[N:4]=1

Participants

4

Reactant 2

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86670119HCID 86670119, compound

Product 1

HCID 86670120HCID 86670120, compoundYield 22%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
120 °C

Procedure

To a 5 mL microwave vial were added 4-(5-bromo-2-chloropyrimidin-4-yl)-N-((S)-1-phenylethyl)morpholine-3-carboxamide (PREPARATION x46, 0.394 g, 0.926 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.024 g, 0.042 mmol), and palladium(II) acetate (6.23 mg, 0.028 mmol). The vessel was evacuated, refilled with nitrogen, and sealed. Dioxane (3.9 mL) was added and the mixture was heated in a microwave to 120° C. for 3 hours. Additional catalyst was added and the reaction mixture was heated in the microwave to 120° C. for another 6 hours. The reaction mixture was then partitioned between aqueous saturated NaHCO3 and ethyl acetate. The aqueous layer was extracted with ethyl acetate and the combined organic layers were dried over MgSO4, filtered, and concentrated. The dark brown crude product was purified by normal phase column chromatography (SiO2, 60 gram) eluting with a gradient of 50-100% EtOAc in hexanes over a 20 minute period. The product-containing fractions were combined and concentrated to give the title compound as a white foam (69 mg, 22%). ESI-MS m/z [M+H]+ calc'd for C17H17ClN4O2, 345.10; found 345.3.

Workup

  1. customThe vessel was evacuated
  2. additionrefilled with nitrogen
  3. customsealed
  4. additionDioxane (3.9 mL) was added
  5. additionAdditional catalyst was added
  6. temperaturethe reaction mixture was heated in the microwave to 120° C. for another 6 hours
  7. customThe reaction mixture was then partitioned between aqueous saturated NaHCO3 and ethyl acetate
  8. extractionThe aqueous layer was extracted with ethyl acetate
  9. dry with materialthe combined organic layers were dried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe dark brown crude product was purified by normal phase column chromatography (SiO2, 60 gram)
  13. washeluting with a gradient of 50-100% EtOAc in hexanes over a 20 minute period
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-9cadf9f068374a4ea8dd4b7e896ea95e
Source dataset
uspto-grants-2015_06
Patent number
US09045496B2

Reaction notes

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