Sodium Bicarbonate → HCID 58504538, compound

HRID 2367292Notes

Reaction equation

HRID 2367292 reaction equation
Cl[C:2]1[CH:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][C@H:9]2[CH3:14])[N:5]=[C:4]([NH2:15])[N:3]=1.[C:16]([C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][C:19]=1[F:27])#[N:17].C([O-])(O)=O.[Na+]>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>[NH2:15][C:4]1[N:3]=[C:2]([C:21]2[CH:22]=[CH:23][C:18]([C:16]#[N:17])=[C:19]([F:27])[CH:20]=2)[CH:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][C@H:9]2[CH3:14])[N:5]=1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 2783130(4-Cyano-3-fluorophenyl)boronic acidHCID 58504423HCID 58504423, compound

Product 1

HCID 58504538HCID 58504538, compoundYield 58.7%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

Into a 25 mL sealable tube under nitrogen were combined 4-chloro-6-[(3R)-3-methyl-4-morpholinyl]-2-pyrimidinamine (500 mg, 2.19 mmol) and (4-cyano-3-fluorophenyl)boronic acid (0.397 g, 2.4 mmol) in 1,4-dioxane (10 mL). Saturated aqueous NaHCO3 (5 mL) was added, and the resulting mixture was degassed with nitrogen for 10 minutes. Pd(Ph3P)4 (0.126 g, 0.11 mmol) was added, the vessel was sealed, and the reaction mixture was stirred at 95° C. overnight. The reaction was cooled to room temperature, solids and other insoluble impurities formed during the reaction were filtered, and the orange filtrate was concentrated. The resulting solid was partitioned between EtOAc and water, and extracted with EtOAc (2×) and CH2Cl2 (2×). The organic layer was separated, washed with water and brine, dried (MgSO4), filtered and concentrated. The resulting solid was dissolved in CH2Cl2 and purified by flash chromatography on SiO2 (gradient: 100% CH2Cl2 to 15% of 90/10/1 CH2Cl2/CH3OH/NH4OH). Fractions were evaporated, and the solids were triturated with Et2O and filtered to afford the title compound (403 mg) as a yellow solid. LC-MS (ES) m/z=314 [M+H]+.

Workup

  1. customInto a 25 mL sealable tube under nitrogen were combined
  2. customthe resulting mixture was degassed with nitrogen for 10 minutes
  3. customthe vessel was sealed
  4. temperatureThe reaction was cooled to room temperature
  5. customsolids and other insoluble impurities formed during the reaction
  6. filtrationwere filtered
  7. concentrationthe orange filtrate was concentrated
  8. customThe resulting solid was partitioned between EtOAc and water
  9. extractionextracted with EtOAc (2×) and CH2Cl2 (2×)
  10. customThe organic layer was separated
  11. washwashed with water and brine
  12. dry with materialdried (MgSO4)
  13. filtrationfiltered
  14. concentrationconcentrated
  15. dissolutionThe resulting solid was dissolved in CH2Cl2
  16. custompurified by flash chromatography on SiO2 (gradient: 100% CH2Cl2 to 15% of 90/10/1 CH2Cl2/CH3OH/NH4OH)
  17. customFractions were evaporated
  18. customthe solids were triturated with Et2O
  19. filtrationfiltered

Sources & evidence

ORD record
ord-d7f5c6c24461416aa2738599d7489edd
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

Loading…