Methanol → 2-chloro-5-fluoro-N-methylpyrimidin-4-amine

HRID 2280978Notes

Reaction equation

HRID 2280978 reaction equation
[F:1][C:2]1[C:3](Cl)=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.CO.[CH3:12][NH2:13].CCOC(C)=O>C(O)C.CCCCCCC>[Cl:8][C:5]1[N:4]=[C:3]([NH:13][CH3:12])[C:2]([F:1])=[CH:7][N:6]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 6329MethylamineHCID 8857Ethyl AcetateHCID 2507052,4-Dichloro-5-fluoropyrimidine

Product 1

HCID 50723072-chloro-5-fluoro-N-methylpyrimidin-4-amine

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8900HeptaneSolvent

Procedure

To a 250 mL round bottom flask equipped with a stir bar was added 9.0 g 5-fluoro-2,4-dichloro-pyrimidine, 40 mL methanol and 15 mL of 8M methylamine in ethanol. The reaction heated up (mild exo-therm) and was allowed to stir at room temperature for ˜30 minutes. A check by TLC (1:1 EtOAc:heptane) and LCMS showed complete reaction. The reaction was concentrated down to give 9.77 g crude material which was purified on a silica column running a gradient of 1% to 10% MeOH in DCM over 35 minutes to give 6.77 g pure 2-chloro-5-fluoro-N-methylpyrimidin-4-amine.

Workup

  1. customTo a 250 mL round bottom flask equipped with a stir bar
  2. temperatureThe reaction heated up (mild exo-therm)
  3. customreaction
  4. concentrationThe reaction was concentrated down
  5. customto give 9.77 g crude material which
  6. customwas purified on a silica column
  7. customover 35 minutes

Sources & evidence

ORD record
ord-8f7a26d092ab4ba48989a1642d194c88
Source dataset
uspto-grants-2015_09
Patent number
US09139566B2

Reaction notes

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