Water → HCID 86669618, compound

HRID 1398710Notes

Reaction equation

HRID 1398710 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH2:8])[CH:5]=[CH:4][N:3]=1.[H-].[Na+].[Br:11][C:12]1[CH:17]=[C:16](F)[C:15]([N+:19]([O-:21])=[O:20])=[CH:14][C:13]=1[F:22].O>C1COCC1.CO>[Br:11][C:12]1[C:13]([F:22])=[CH:14][C:15]([N+:19]([O-:21])=[O:20])=[C:16]([NH:8][C:6]2[CH:5]=[CH:4][N:3]=[C:2]([Cl:1])[N:7]=2)[CH:17]=1

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 3457522-Chloro-4-aminopyrimidineHCID 27362864-Bromo-2,5-difluoronitrobenzene

Product 1

HCID 86669618HCID 86669618, compoundYield 57.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-chloropyrimidin-4-amine (1.31 g, 10.08 mmol) in THF (55 mL) at 0° C. was added sodium hydride (60% in oil, 806.69 mg, 20.17 mmol) portion-wise. The reaction mixture was stirred at 0° C. to RT for 10 minutes and 1-bromo-2,5-difluoro-4-nitrobenzene (1.2 g, 5.04 mmol) was added. The reaction mixture was stirred at 65° C. for 1 h. The reaction mixture was cooled to RT and water (30 mL) was added. Product extracted into DCM (2×30 mL) and washed with water (20 mL). The combined organics were dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by column chromatography (Biotage) eluted with DCM:MeOH gradient (99:1 to 95:05) to afford the title compound as an orange solid (1005 mg, 56% yield); 1H NMR (250 MHz, DMSO) delta 6.87 (1H, d, J=5.83 Hz), 8.08 (1H, d, J=6.31 Hz), 8.18 (1H, d, J=8.35 Hz), 8.27 (1H, d, J=5.83 Hz), 10.32 (1H, br. s.); LC-MS: m/z+348.70 (M+H)+.

Workup

  1. stirringThe reaction mixture was stirred at 65° C. for 1 h
  2. extractionProduct extracted into DCM (2×30 mL)
  3. washwashed with water (20 mL)
  4. dry with materialThe combined organics were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by column chromatography (Biotage)
  8. washeluted with DCM

Sources & evidence

ORD record
ord-342d6ea1133241a9af9d7f8e841caf3b
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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