Diglyme → 4-Amino-6-(2-fluoro-4-nitrophenoxy)pyrimidine

HRID 2237162Notes

Reaction equation

HRID 2237162 reaction equation
COC1C=C(OC)C=C(OC)C=1C[NH:6][C:7]1[CH:12]=[C:11](Cl)[N:10]=[CH:9][N:8]=1.[F:22][C:23]1[CH:28]=[C:27]([N+:29]([O-:31])=[O:30])[CH:26]=[CH:25][C:24]=1[OH:32].COCCOCCOC>O>[F:22][C:23]1[CH:28]=[C:27]([N+:29]([O-:31])=[O:30])[CH:26]=[CH:25][C:24]=1[O:32][C:11]1[N:10]=[CH:9][N:8]=[C:7]([NH2:6])[CH:12]=1

Participants

5

Reactant 3

HCID 8150DiglymeHCID 98252-Fluoro-4-nitrophenolHCID 59852864HCID 59852864, compound

Product 1

HCID 231530124-Amino-6-(2-fluoro-4-nitrophenoxy)pyrimidineYield 31%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
160 °C

Procedure

A mixture of N-(2,4,6-trimethoxybenzyl)-6-chloropyrimidin-4-amine (2.2 g, 7.11 mmol), 2-fluoro-4-nitrophenol (1.1 g, 7.0 mmol), and 2-methoxyethyl ether (50 mL) was heated at 160° C. for 60 h. The reaction mixture was cooled to RT and poured into H2O (200 mL). The solid was collected, washed with 2 M aqueous Na2CO3 and H2O, and then vacuum dried on a Büchner funnel. The crude product was treated with TFA (20 mL) in dioxane (40 mL) and stirred at RT for 4 h. The reaction mixture was concentrated, the residue partitioned between EtOAc and saturated NaHCO3 solution. The EtOAc phase was separated, dried (MgSO4), concentrated and the crude product purified by flash chromatography using 1-2% MeOH in CH2Cl2 as the eluent to give 6-(2-fluoro-4-nitrophenoxy)pyrimidin-4-amine (440 mg, 31%). 1H NMR (DMSO-d6) δ 8.31 (dd, 1H, J=10.4, 2.5 Hz), 8.14 (dd, 1H, J=9.8, 2.0 Hz), 8.04 (s, 1H), 7.61 (dd, 1H, J=8.3, 8.3 Hz), 7.07 (s, 2H), 6.02 (s, 1H); MS(ESI+) m/z 251.15 (M+H)+.

Workup

  1. temperatureThe reaction mixture was cooled to RT
  2. customThe solid was collected
  3. washwashed with 2 M aqueous Na2CO3 and H2O
  4. customvacuum dried on a Büchner funnel
  5. additionThe crude product was treated with TFA (20 mL) in dioxane (40 mL)
  6. concentrationThe reaction mixture was concentrated
  7. customthe residue partitioned between EtOAc and saturated NaHCO3 solution
  8. customThe EtOAc phase was separated
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated
  11. customthe crude product purified by flash chromatography

Sources & evidence

ORD record
ord-f632293369ba4fb1a4f0a352b8e94726
Source dataset
uspto-grants-2010_05
Patent number
US07714138B2

Reaction notes

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