2-Amino-4,6-dichloropyrimidine → HCID 51354897, compound

HRID 2367197Notes

Reaction equation

HRID 2367197 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][C:4]=1[F:12])#[N:2].[Cl:13][C:14]1[CH:19]=[C:18](Cl)[N:17]=[C:16]([NH2:21])[N:15]=1.C([O-])(O)=O.[Na+]>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.O1CCOCC1>[NH2:21][C:16]1[N:17]=[C:18]([C:6]2[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[C:4]([F:12])[CH:5]=2)[CH:19]=[C:14]([Cl:13])[N:15]=1

Participants

6

Reactant 3

HCID 655222-Amino-4,6-dichloropyrimidineHCID 516892Sodium BicarbonateHCID 2783130(4-Cyano-3-fluorophenyl)boronic acid

Product 1

HCID 51354897HCID 51354897, compoundYield 35.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

In a 25 mL sealable tube under argon were combined (4-cyano-3-fluorophenyl)boronic acid (0.50 g, 3.03 mmol), 4,6-dichloro-2-pyrimidinamine (0.497 g, 3.03 mmol), saturated aqueous NaHCO3 (4.04 mL), and 1,4-dioxane (16.2 mL), and the mixture was degassed with argon for 5 minutes. Pd(Ph3P)4 (0.175 g, 0.152 mmol) was added, the vial was sealed, and the reaction mixture was stirred for 16 hours at 95° C. The reaction was cooled to room temperature, filtered through a plug of celite503, and concentrated. The resulting orange tar was partitioned between EtOAc and water. The organic layer was separated, washed with brine, dried (MgSO4), filtered and concentrated. The resulting orange solid was sonicated in CHCl3 (50 mL) for 2 minutes. The mixture was filtrated, the solid was washed with CHCl3, and the filtrate was concentrated. Flash chromatography on SiO2 (40 g) of the resulting residue (gradient: 100% CHCl3 to 5% EtOAc/CHCl3) afforded the title compound (267 mg, 32%) as a yellow solid. LC-MS (ES) m/z=249 [M+H]+.

Workup

  1. customIn a 25 mL sealable tube under argon were combined
  2. customthe vial was sealed
  3. temperatureThe reaction was cooled to room temperature
  4. filtrationfiltered through a plug of celite503
  5. concentrationconcentrated
  6. customThe resulting orange tar was partitioned between EtOAc and water
  7. customThe organic layer was separated
  8. washwashed with brine
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe resulting orange solid was sonicated in CHCl3 (50 mL) for 2 minutes
  13. filtrationThe mixture was filtrated
  14. washthe solid was washed with CHCl3
  15. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-c4c6c2bca15744148da876b4f3b1213b
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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