Phosphorus oxychloride → 2-Amino-5-fluoro-4-chloro-1-methyl-6-oxo-1,6-dihydropyridine-carbonitrile

HRID 2090554Notes

Reaction equation

HRID 2090554 reaction equation
[NH2:1][C:2]1([C:12]#[N:13])[CH2:7][C:6](O)=[C:5]([F:9])[C:4](=[O:10])[N:3]1[CH3:11].P(Cl)(Cl)([Cl:16])=O>C(#N)C>[NH2:1][C:2]1([C:12]#[N:13])[CH2:7][C:6]([Cl:16])=[C:5]([F:9])[C:4](=[O:10])[N:3]1[CH3:11]

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 673786932-Amino-5-fluoro-4-hydroxy-1-methyl-6-oxo-1,6-dihydropyridine-carbonitrile

Product 1

HCID 673782282-Amino-5-fluoro-4-chloro-1-methyl-6-oxo-1,6-dihydropyridine-carbonitrile

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

Combine 2-amino-5-fluoro-4-hydroxy-1-methyl-6-oxo-1,6-dihydropyridine-carbonitrile (30.0 g, 0.164 mol) and anhydrous acetonitrile (150 mL). Slowly add phosphorous oxychloride (37 mL). After addition is complete heat to reflux. After 3 hours, cool to ambient temperature and then in an ice-bath. Add another portion of acetonitrile (150 mL). Slowly add to ice-water (300 mL, 10 volumes). Heat to about 50° C. After 5 hours, cool in an ice bath to give a solid, filter, rinse the solid with water, and dry in vacuo to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ7.73 (s, 2H). 3.33 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ153.3 (d, J=32.9 Hz), 139.2, 136.9, 128.5 (d, J=16.9 Hz), 115.3 (d, J=2.2 Hz), 68.1, 29.7 (d, J=1.4 Hz); 19F NMR (376 MHz, DMSO-d6) δ−152.0; MS (M+H)+m/z calcd 202.0. found 202.0. Combine the title compound (4.4 g) in 40 mL of dimethylacetamide (40 mL) and heat to 38° C. Add activated carbon (4.4 g). After 30 minutes filter through Celite®, rinse with dimethylacetamide, and add water to the filtrate, then cool in an ice bath to give a solid. Collect the solid by filtration, rinse with water (20 mL), and dry in vacuo at give the title compound.

Workup

  1. additionAfter addition
  2. temperatureis complete heat to reflux
  3. temperatureHeat to about 50° C
  4. waitAfter 5 hours
  5. temperaturecool in an ice bath
  6. customto give a solid
  7. filtrationfilter
  8. washrinse the solid with water
  9. customdry in vacuo

Sources & evidence

ORD record
ord-1bbbb93c18e640cbb8975412a182c26f
Source dataset
uspto-grants-2013_05
Patent number
US08436200B2

Reaction notes

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