2,4-Dichloro-5-fluoropyrimidine → 2-chloro-5-fluoro-N4-[4-(prop-2-ynyloxy)phenyl]-4-pyrimidineamine

HRID 1947625Notes

Reaction equation

HRID 1947625 reaction equation
[CH2:1]([O:4][C:5]1[CH:11]=[CH:10][C:8]([NH2:9])=[CH:7][CH:6]=1)[C:2]#[CH:3].[Cl:12][C:13]1[N:18]=[C:17](Cl)[C:16]([F:20])=[CH:15][N:14]=1>CO.O.CCOC(C)=O>[Cl:12][C:13]1[N:18]=[C:17]([NH:9][C:8]2[CH:10]=[CH:11][C:5]([O:4][CH2:1][C:2]#[CH:3])=[CH:6][CH:7]=2)[C:16]([F:20])=[CH:15][N:14]=1

Participants

5

Reactant 2

HCID 2507052,4-Dichloro-5-fluoropyrimidineHCID 126688624-(Prop-2-yn-1-yloxy)aniline

Product 1

HCID 575628992-chloro-5-fluoro-N4-[4-(prop-2-ynyloxy)phenyl]-4-pyrimidineamineYield 243.6%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 22242641Methanol--water (1/1)Solvent

Procedure

Crude 4-(prop-2-ynyloxy)aniline (0.750 g, 5.10 mmol) and 2,4-dichloro-5-fluoropyrimidine (1.27 g, 0.760 mmol) were stirred in MeOH/water (4:1, 35 mL) at room temperature for 18 h. The reaction mixture was diluted with EtOAc (200 mL) and washed with 1N HCl (50 mL) and brine (50 mL). The organic layer was dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (silica gel, hexanes ramped to EtOAc:hexanes (1:10)) to provide 2-chloro-5-fluoro-N4-[4-(prop-2-ynyloxy)phenyl]-4-pyrimidineamine as a light brown solid (0.514 g). 1H NMR (CDCl3): δ 8.03 (d, J=2.7 Hz, 1H), 7.53 (d, J=8.7 Hz, 2H), 7.02 (d, J=8.7 Hz, 2H), 6.86 (s, 1H), 4.71 (d, J=2.4 Hz, 2H), 2.55 (t, J=2.4 Hz, 1H); LCMS: purity: 99%; MS (m/e): 279 (MH+).

Workup

  1. washwashed with 1N HCl (50 mL) and brine (50 mL)
  2. dry with materialThe organic layer was dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatography (silica gel, hexanes ramped to EtOAc:hexanes (1:10))

Sources & evidence

ORD record
ord-35930ece3fb04fd5bca630f29d5dc547
Source dataset
uspto-grants-2013_03
Patent number
US08399472B2

Reaction notes

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