2,4-Dichloro-5-fluoropyrimidine → HCID 58956313, compound

HRID 1853437Notes

Reaction equation

HRID 1853437 reaction equation
[CH2:1]([NH:4][S:5]([CH2:8][C:9]1[CH:15]=[CH:14][C:12]([NH2:13])=[CH:11][CH:10]=1)(=[O:7])=[O:6])[C:2]#[CH:3].[Cl:16][C:17]1[N:22]=[C:21](Cl)[C:20]([F:24])=[CH:19][N:18]=1>CO.O.C(OCC)(=O)C>[Cl:16][C:17]1[N:22]=[C:21]([NH:13][C:12]2[CH:11]=[CH:10][C:9]([CH2:8][S:5]([NH:4][CH2:1][C:2]#[CH:3])(=[O:6])=[O:7])=[CH:15][CH:14]=2)[C:20]([F:24])=[CH:19][N:18]=1

Participants

5

Reactant 2

HCID 2507052,4-Dichloro-5-fluoropyrimidineHCID 58956317HCID 58956317, compound

Product 1

HCID 58956313HCID 58956313, compoundYield 45.8%

Reagents, catalysts & solvents 2

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

Procedure

4-(Prop-2-ynylaminosulfonylmethyl)aniline (0.353 g, 1.57 mmol) and 2,4-dichloro-5-fluoropyrimidine (0.471 g, 2.81 mmol) were stirred in methanol:water (4:1, 10 mL) at room temperature for 24 h. The reaction mixture was diluted with ethyl acetate (75 mL) and washed with 1N HCl (25 mL) and brine (10 mL). The organic layer was dried (MgSO4), filtered, and concentrated in vacuo. The residue was purified by column chromatography (silica gel, dichloromethane ramped to methanol:dichloromethane (3:100)) to provide 2-chloro-5-fluoro-N4-[4-(prop-2-ynylaminosulfonylmethyl)phenyl]-4-pyrimidineamine as an off-white solid (0.255 g). 1H NMR (DMSO-d6): δ 10.03 (s, 1H), 8.31 (d, J=3.0 Hz, 1H), 7.68-7.63 (m, 3H), 7.36 (d, J=8.4 Hz, 2H), 4.35 (s, 2H), 3.78 (dd, J=2.4 and 5.7 Hz, 2H), 3.34 (t, J=2.4 Hz, 1H); LCMS: purity: 90%; MS (m/e): 356 (MH+).

Workup

  1. washwashed with 1N HCl (25 mL) and brine (10 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, dichloromethane ramped to methanol:dichloromethane (3:100))

Sources & evidence

ORD record
ord-d1faa512e7dc4212b7a04549d3989f4e
Source dataset
uspto-grants-2015_02
Patent number
US08962643B2

Reaction notes

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