Potassium Carbonate → HCID 58514514, compound

HRID 341297Notes

Reaction equation

HRID 341297 reaction equation
B(O)O.C([O-])([O-])=O.[K+].[K+].[CH:10]1[CH:15]=[C:14]2[C:16]3[CH:22]=[CH:21][C:20](Cl)=[N:19][C:17]=3[NH:18][C:13]2=[CH:12][CH:11]=1>O.O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH:18]1[CH:13]=[CH:14][CH:16]=[C:17]1[C:20]1[CH:21]=[CH:22][C:16]2[C:14]3[C:13](=[CH:12][CH:11]=[CH:10][CH:15]=3)[NH:18][C:17]=2[N:19]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 61668Boronic AcidHCID 13897940HCID 13897940, compound

Product 1

HCID 58514514HCID 58514514, compoundYield 10%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

At room temperature and under an inert atmosphere, Pd(PPh3)4 (0.08 equiv.), boronic acid (1.1 equiv.), and a 0.3 M solution of K2CO3 (3 equiv.) in H2O were added to a 0.1M solution of 2-chloro-α-carboline in anhydrous 1,4-dioxane. This solution was stirred at 100° C. for 12 h. After cooling to room temperature, the solution was filtered through celite and solvents were removed under reduced pressure. A solution of crude product in CH2Cl2 (3.5 mL) was stirred under argon and treated with CF3CO2H (1 mL). After 90 min at room temperature, the resulting mixture was then cautiously quenched at 0° C. with H2O and a saturated aqueous NaHCO3 was added until pH 10. The solution was diluted with CH2Cl2, washed with H2O, dried with MgSO4, filtered and concentrated. The product was purified by column chromatography on silica gel (CH2Cl2) to afford R355 in 10% yield as a yellow solid. 1H-NMR (300 MHz, CDCl3): δ 9.90 (bs, 1H), 8.89 (bs, NH), 8.28 (d, 1H, J=8.0 Hz), 7.98 (d, 1H, J=8.0 Hz), 7.51 (d, 1H, J=8.1 Hz), 7.43-7.40 (m, 1H); 7.33-7.27 (m, 2H), 6.97 (s, 1H), 6.85 (s, 1H), 6.34 (dd, 1H, J=2.6, 5.5 Hz).

Workup

  1. temperatureAfter cooling to room temperature
  2. filtrationthe solution was filtered through celite and solvents
  3. customwere removed under reduced pressure
  4. stirringA solution of crude product in CH2Cl2 (3.5 mL) was stirred under argon
  5. additiontreated with CF3CO2H (1 mL)
  6. waitAfter 90 min at room temperature
  7. customthe resulting mixture was then cautiously quenched at 0° C. with H2O
  8. additiona saturated aqueous NaHCO3 was added until pH 10
  9. additionThe solution was diluted with CH2Cl2
  10. washwashed with H2O
  11. dry with materialdried with MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe product was purified by column chromatography on silica gel (CH2Cl2)
  15. customto afford R355 in 10% yield as a yellow solid

Sources & evidence

ORD record
ord-d04781e87e2244fba1da04e74bfc541b
Source dataset
uspto-grants-2014_11
Patent number
US08895744B2

Reaction notes

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