Sodium Bicarbonate → HCID 58504644, compound

HRID 2367286Notes

Reaction equation

HRID 2367286 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH2:8])[N:5]=[C:4]([NH:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH:3]=1.[C:14]([C:16]1[CH:21]=[CH:20][C:19](B(O)O)=[CH:18][C:17]=1[F:25])#[N:15].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>[NH2:8][C:6]1[N:7]=[C:2]([C:19]2[CH:20]=[CH:21][C:16]([C:14]#[N:15])=[C:17]([F:25])[CH:18]=2)[CH:3]=[C:4]([NH:9][C:10]([CH3:13])([CH3:12])[CH3:11])[N:5]=1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 2783130(4-Cyano-3-fluorophenyl)boronic acidHCID 19073890HCID 19073890, compound

Product 1

HCID 58504644HCID 58504644, compoundYield 88.5%

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 6-chloro-N4-(1,1-dimethylethyl)-2,4-pyrimidinediamine (440 mg, 2.19 mmol) and (4-cyano-3-fluorophenyl)boronic acid (0.416 g, 2.52 mmol) in 1,4-dioxane (8 mL). Saturated aqueous NaHCO3 (4 mL) was added, and the resulting mixture was degassed with nitrogen for 10 minutes. Pd(Ph3P)4 (0.127 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 combined organic layers were washed with water and brine, dried (MgSO4), filtered and concentrated. The resulting solid was dissolved in DMSO and purified on a Gilson RPHPLC (CH3CN/H2O w/0.1% TFA). Fractions were evaporated and solids were triturated in Et2O and filtered to afford the title compound (553 mg). LC-MS (ES) m/z=286 [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. washThe combined organic layers were washed with water and brine
  11. dry with materialdried (MgSO4)
  12. filtrationfiltered
  13. concentrationconcentrated
  14. dissolutionThe resulting solid was dissolved in DMSO
  15. custompurified on a Gilson RPHPLC (CH3CN/H2O w/0.1% TFA)
  16. customFractions were evaporated
  17. customsolids were triturated in Et2O
  18. filtrationfiltered

Sources & evidence

ORD record
ord-9fb22a4229994732851be2af79cfb41b
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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