Potassium Phosphate, Tribasic → HCID 86651587, compound

HRID 2169580Notes

Reaction equation

HRID 2169580 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][CH:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)=[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.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>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]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[C:15](=[O:16])[CH:10]3[CH2:11][O:12][CH2:13][CH2:14][N:9]3[C:3]=2[N:4]=1

Participants

5

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86670123HCID 86670123, compound

Product 1

HCID 86651587HCID 86651587, compoundYield 76.1%

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-(tetrahydro-2H-pyran-4-yl)morpholine-3-carboxamide (PREPARATION x54, 320 mg, 0.789 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (34.2 mg, 0.059 mmol), palladium(II) acetate (8.85 mg, 0.039 mmol), and potassium phosphate, tribasic (234 mg, 1.104 mmol). The vessel was sealed, evacuated, and refilled with nitrogen. To the vessel were added dioxane (2 mL) and tert-butanol (0.500 mL), and the mixture was heated in a microwave to 120° C. for 6 hours. The reaction mixture was subsequently partitioned between saturated brine and ethyl acetate. The aqueous layer was extracted with ethyl acetate and the combined organic layers were dried over MgSO4, filtered, and concentrated. The crude product was purified by normal phase column chromatography (SiO2, 50-100% EtOAc gradient in hexanes over 20 minutes) to give the title compound (195 mg, 76%).

Workup

  1. customThe vessel was sealed
  2. customevacuated
  3. additionrefilled with nitrogen
  4. additionTo the vessel were added dioxane (2 mL) and tert-butanol (0.500 mL)
  5. customThe reaction mixture was subsequently partitioned between saturated brine and ethyl acetate
  6. extractionThe aqueous layer was extracted with ethyl acetate
  7. dry with materialthe combined organic layers were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by normal phase column chromatography (SiO2, 50-100% EtOAc gradient in hexanes over 20 minutes)

Sources & evidence

ORD record
ord-8f3747b44b444e7294032dbd98b1b211
Source dataset
uspto-grants-2015_06
Patent number
US09045496B2

Reaction notes

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