Potassium Phosphate, Tribasic → HCID 68291675, compound

HRID 1507955Notes

Reaction equation

HRID 1507955 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9]([S:10][CH2:11][CH3:12])=[C:8]([C:13]([NH2:15])=[O:14])[CH:7]=[N:6][N:5]2[CH:16]=1.[C:17]1(B(O)O)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:11]([S:10][C:9]1[C:4]2[N:5]([CH:16]=[C:2]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH:3]=2)[N:6]=[CH:7][C:8]=1[C:13]([NH2:15])=[O:14])[CH3:12]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, Tribasic2×HCID 66827Phenylboronic Acid2×HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 68291682HCID 68291682, compound

Product 1

HCID 68291675HCID 68291675, compoundYield 77%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalyst2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
125 °C

Procedure

A mixture of 6-bromo-4-(ethylthio)pyrrolo[1,2-b]pyridazine-3-carboxamide (1.2 g, 4.00 mmol), phenylboronic acid (0.731 g, 6.00 mmol), palladium (II) acetate (0.090 g, 0.400 mmol), 2M potassium phosphate, tribasic (7.60 mL, 15.19 mmol) and 2-(dicyclohexylphosphino)-2′,4′,6′-triisopropylbyphenyl (0.381 g, 0.800 mmol) in dioxane (volume: 30 mL) was heated to 125° C. in a pressure vessel, behind a blast shield for 4 hr. Additional phenylboronic acid (0.366 g, 3.00 mmol), palladium (II) acetate (0.045 g, 0.200 mmol), 2-(dicyclohexylphosphino)-2′,4′,6′-triisopropylbiphenyl (0.191 g, 0.400 mmol) and 2M potassium phosphate, tribasic (7.60 mL, 15.19 mmol) were added and heating was continued for 1 hr. The reaction mixture was partitioned between EtOAc (250 ml) and water (250 ml). The organic layer was washed with brine (100 ml), dried (MgSO4) and concentrated to a yellow solid that was triturated with ethyl ether. Filtration, washing with ethyl ether/hexane, 1:1 and drying afforded the title compound (0.91 g, 3.06 mmol, 77% yield) as a yellow solid that was used in the next step without further purification. 1H NMR (400 MHz, MeOD) δ ppm 1.28 (t, J=7.4 Hz, 3 H) 3.19 (q, J=7.5 Hz, 2 H) 7.23 (d, J=1.8 Hz, 1 H) 7.28 (d, J=7.5 Hz, 1 H) 7.40 (t, J=7.7 Hz, 2 H) 7.74 (d, J=7.3 Hz, 2 H) 8.16 (s, 1 H) 8.21 (d, J=1.8 Hz, 1 H). LCMS (M+H)=298.07.

Workup

  1. temperatureheating
  2. customThe reaction mixture was partitioned between EtOAc (250 ml) and water (250 ml)
  3. washThe organic layer was washed with brine (100 ml)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated to a yellow solid
  6. customthat was triturated with ethyl ether
  7. filtrationFiltration
  8. washwashing with ethyl ether/hexane, 1:1
  9. customdrying

Sources & evidence

ORD record
ord-da9c4cba298d473db5eedd03bf5bcb92
Source dataset
uspto-grants-2015_12
Patent number
US09221826B2

Reaction notes

Loading…