Phosphorus oxychloride → HCID 117702910, compound

HRID 873939Notes

Reaction equation

HRID 873939 reaction equation
[CH3:1][O:2][C:3]1[C:4]([NH:12][NH:13][C:14](=O)[CH3:15])=[N:5][CH:6]=[C:7]([N+:9]([O-:11])=[O:10])[CH:8]=1.CCN(C(C)C)C(C)C.O=P(Cl)(Cl)Cl.C([O-])(O)=O.[Na+]>CC#N.O>[CH3:1][O:2][C:3]1[C:4]2[N:5]([C:14]([CH3:15])=[N:13][N:12]=2)[CH:6]=[C:7]([N+:9]([O-:11])=[O:10])[CH:8]=1

Participants

7

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 117702704HCID 117702704, compound

Product 1

HCID 117702910HCID 117702910, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

To a suspension of N′-(3-methoxy-5-nitropyridin-2-yl)acetohydrazide (Step 84.2) (23.3 g, 84 mmol) in CH3CN (200 mL) was added DIEA (11.1 mL, 63.3 mmol) and dropwise POCl3 (11.8 mL, 127 mmol) and the reaction mixture was stirred for 3.5 hr at 90° C. The cooled mixture was slowly added to water (600 mL), stirred for 30 min before the mixture was neutralized with solid NaHCO3 to pH 6.5. The product was extracted with CH2Cl2/MeOH 6:1. Combined extracts were washed with H2O, dried over MgSO4, filtered and concentrated under reduced pressure. The crude material was purified by silica gel column chromatography (hexane/EtOAc/MeOH 50:50:5 to 0:50:5) followed by recrystallization from CH2Cl2/EtOAc/Et2O. tR: 0.49 min (LC-MS 2); ESI-MS: 209 [M+H]+ (LC-MS 2); 1H NMR (400 MHz, DMSO-d6) δ ppm 2.79 (s, 3H) 4.10 (s, 3H) 7.29 (d, J=1.7 Hz, 1H) 9.25 (d, J=1.7 Hz, 1H).

Workup

  1. stirringstirred for 30 min before the mixture
  2. extractionThe product was extracted with CH2Cl2/MeOH 6:1
  3. washCombined extracts were washed with H2O
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude material was purified by silica gel column chromatography (hexane/EtOAc/MeOH 50:50:5 to 0:50:5)
  8. customfollowed by recrystallization from CH2Cl2/EtOAc/Et2O

Sources & evidence

ORD record
ord-8f8723f587334eb6ae0c060fc19c8c87
Source dataset
uspto-grants-2015_03
Patent number
US08975417B2

Reaction notes

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