Potassium Phosphate, Tribasic → HCID 25234717, compound

HRID 1924449Notes

Reaction equation

HRID 1924449 reaction equation
Br[C:2]1[C:3]([O:29][CH3:30])=[C:4]([CH:18]=[C:19]([N:21]2[CH:26]=[CH:25][C:24](=[O:27])[NH:23][C:22]2=[O:28])[CH:20]=1)/[CH:5]=[CH:6]/[C:7]1[CH:12]=[CH:11][C:10]([NH:13][S:14]([CH3:17])(=[O:16])=[O:15])=[CH:9][CH:8]=1.[S:31]1[CH:35]=[CH:34][CH:33]=[C:32]1B(O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1COCC1.O.[Pd](Cl)Cl.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2]>[O:28]=[C:22]1[NH:23][C:24](=[O:27])[CH:25]=[CH:26][N:21]1[C:19]1[CH:20]=[C:2]([C:32]2[S:31][CH:35]=[CH:34][CH:33]=2)[C:3]([O:29][CH3:30])=[C:4]([CH:18]=1)/[CH:5]=[CH:6]/[C:7]1[CH:12]=[CH:11][C:10]([NH:13][S:14]([CH3:17])(=[O:16])=[O:15])=[CH:9][CH:8]=1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27339602-Thiopheneboronic acidHCID 25234722HCID 25234722, compound

Product 1

HCID 25234717HCID 25234717, compoundYield 50%

Reagents, catalysts & solvents 3

HCID 178454861HCID 178454861, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a 5 ml microwave tube was added the product from Example 15, Part D (40 mg, 0.081 mmol), thiophen-2-ylboronic acid (10.40 mg, 0.081 mmol), 1,1′-bis(di-tert-butylphosphino)ferrocene palladium dichloride (2.65 mg, 4.06 μmol) and potassium phosphate (34.5 mg, 0.162 mmol) in THF (3.0 ml) and water (1.0 ml). The vessel was sealed and the mixture was sparged by nitrogen for 5 min and heated at 50° C. for 3 h. The mixture was partitioned with ethyl acetate and 1M HCl. The organic layer was washed with saturated sodium bicarbonate, brine, dried with sodium sulfate and filtered. The filtrate was treated with 3-mercaptopropyl functionalized silica gel, filtered through celite and evaporated. The residue was purified by reverse phase chromatography to give the title compound as a white solid (20 mg, 50%). 1H NMR (300 MHz, DMSO-d6) δ ppm 3.03 (s, 3 H) 3.70 (s, 3 H) 5.70 (dd, J=7.72, 2.21 Hz, 1 H) 7.18 (dd, J=5.43, 4.05 Hz, 1 H) 7.25 (d, J=8.82 Hz, 2 H) 7.35 (s, 2 H) 7.63 (d, J=8.82 Hz, 2 H) 7.68 (m, 2 H) 7.77 (m, 2 H) 7.83 (d, J=7.72 Hz, 1 H) 9.89 (s, 1 H) 11.49 (d, J=2.21 Hz, 1 H). MS (ESI+) m/z 496 (M+H)+.

Workup

  1. customThe vessel was sealed
  2. customthe mixture was sparged by nitrogen for 5 min
  3. customThe mixture was partitioned with ethyl acetate and 1M HCl
  4. washThe organic layer was washed with saturated sodium bicarbonate, brine
  5. dry with materialdried with sodium sulfate
  6. filtrationfiltered
  7. additionThe filtrate was treated with 3-mercaptopropyl functionalized silica gel
  8. filtrationfiltered through celite
  9. customevaporated
  10. customThe residue was purified by reverse phase chromatography

Sources & evidence

ORD record
ord-769c2cd010c044cc811b27d308a93764
Source dataset
uspto-grants-2012_05
Patent number
US08178548B2

Reaction notes

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