Potassium Phosphate, Dibasic → HCID 89783907, compound

HRID 1056144Notes

Reaction equation

HRID 1056144 reaction equation
OP([O-])([O-])=O.[K+].[K+].[F:8][C:9]1[C:10]([CH3:28])=[N:11][C:12]2[C:17]([N:18]=1)=[C:16](B1OC(C)(C)C(C)(C)O1)[CH:15]=[CH:14][CH:13]=2.Br[C:30]1[NH:34][C:33]2[C@@H:35]([CH3:39])[NH:36][C:37](=[O:38])[C:32]=2[CH:31]=1>CN(C=O)C.O.C(C1C(C(C)(C)C)=C([Pd]Cl)C=CC=1NC)(C)(C)C>[F:8][C:9]1[C:10]([CH3:28])=[N:11][C:12]2[C:17]([N:18]=1)=[C:16]([C:30]1[NH:34][C:33]3[C@@H:35]([CH3:39])[NH:36][C:37](=[O:38])[C:32]=3[CH:31]=1)[CH:15]=[CH:14][CH:13]=2

Participants

7

Reactant 3

HCID 24450Potassium Phosphate, DibasicHCID 89783327HCID 89783327, compoundHCID 89783900HCID 89783900, compound

Product 1

HCID 89783907HCID 89783907, compoundYield 42.6%

Reagents, catalysts & solvents 3

HCID 178482226HCID 178482226, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Argon was bubbled into a slurry of potassium phosphate dibasic (Aldrich; 0.164 g, 0.944 mmol), 1,1-bis[(di-t-butyl-p-methylaminophenyl]palladium(ii) chloride (Aldrich; 0.019 g, 0.027 mmol), 3-fluoro-2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoxaline (618) (0.155 g, 0.539 mmol), (R)-2-bromo-6-methyl-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one (287) (0.058 g, 0.270 mmol) in 1.5 mL DMF and 0.5 mL water for 1 min. The reaction was sealed and placed in a 70° C. oil bath for 45 min. Additional 1 equiv boronic ester and 5 mg catalyst added, and the reaction was heated 30 min additional. The reaction was partitioned between water and EtOAc. The aq. layer was extracted 1× EtOAc, and the combined organic layers were washed with water 2 times, saturated aq. NaCl once, and the organics were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The material was treated with DCM and purified by silica gel chromatography (24 g column) using 0-100% 90/10 DCM/MeOH in DCM. The product-containing fractions were concentrated to afford (R)-2-(3-fluoro-2-methylquinoxalin-5-yl)-6-methyl-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one (287f; 0.034 g, 0.115 mmol, 42% yield) as a orange solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.90 (1H, s), 8.07 (1H, d, J=7.6 Hz), 7.94 (1H, d, J=8.2 Hz), 7.78-7.88 (1H, m), 7.69 (1H, s), 7.01 (1H, d, J=1.6 Hz), 4.58 (1H, q, J=6.7 Hz), 2.71 (3H, s), 1.41 (3H, d, J=6.7 Hz). m/z (ESI, +ve) 297.0 (M+H)+.

Workup

  1. customThe reaction was sealed
  2. customplaced in a 70° C.
  3. customfor 45 min
  4. temperaturethe reaction was heated 30 min additional
  5. customThe reaction was partitioned between water and EtOAc
  6. extractionThe aq. layer was extracted 1× EtOAc
  7. washthe combined organic layers were washed with water 2 times, saturated aq. NaCl once
  8. dry with materialthe organics were dried over anhydrous Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. additionThe material was treated with DCM
  12. custompurified by silica gel chromatography (24 g column)
  13. concentrationThe product-containing fractions were concentrated

Sources & evidence

ORD record
ord-d47c17ac680d45e7917fd14bdcb20270
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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