Phosphorus oxychloride → HCID 86711220, compound

HRID 1475950Notes

Reaction equation

HRID 1475950 reaction equation
C[C:2](C)=[CH:3][CH:4]=[O:5].O=P(Cl)(Cl)Cl.[CH2:12]([N:17]([CH2:37][CH2:38][CH:39]([CH3:41])[CH3:40])[C:18]([C:20]1[CH:25]=[CH:24][N:23]2[N:26]=[C:27]([C:29]([N:31]3[CH2:36][CH2:35]C[CH2:33][CH2:32]3)=[O:30])[CH:28]=[C:22]2[CH:21]=1)=[O:19])[CH2:13][CH:14]([CH3:16])[CH3:15].C(=O)(O)[O-:43].[Na+].[NH4+].[Cl-]>ClC(Cl)C.CO.O>[CH2:12]([N:17]([CH2:37][CH2:38][CH:39]([CH3:41])[CH3:40])[C:18]([C:20]1[CH:25]=[CH:24][N:23]2[N:26]=[C:27]([C:29]([N:31]3[CH2:32][CH2:33][O:43][CH2:35][CH2:36]3)=[O:30])[C:28](/[CH:2]=[CH:3]/[CH:4]=[O:5])=[C:22]2[CH:21]=1)=[O:19])[CH2:13][CH:14]([CH3:16])[CH3:15]

Participants

9

Reactant 5

HCID 24813Phosphorus oxychlorideHCID 25517Ammonium ChlorideHCID 610203-Methyl-2-butenalHCID 516892Sodium BicarbonateHCID 68276042HCID 68276042, compound

Product 1

HCID 86711220HCID 86711220, compoundYield 78%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
65 °C

Procedure

To a stirred solution of dimethylacroleine (0.250 ml, 2.52 mmol) and POCl3 (0.235 ml, 2.52 mmol) in dichloroethane (2 ml) at 0° C. for 15 min was added N,N-diisopentyl-2-(piperidine-1-carbonyl)pyrazolo[1,5-a]pyridine-5-carboxamide (0.26 g, 0.630 mmol). The mixture was heated to 65° C. for 6 h. Mixed more reagents for 15 min then added to solution above and stirred at 65° C. for 12 h. Water (20 ml) was added to the cooled mixture and extracted with DCM (3×25 ml). The combined organics (liquids and solids) were concentrated to afford a red semisolid. The residue was treated with saturated sodium bicarbonate (20 ml) and MeOH (20 ml) overnight. The suspension was neutralized with a saturated NH4Cl solution and extracted with DCM (3×100 ml). The combined organics were dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography: ISCO 24 g eluting with 0% to 100% ethyl acetate in hexanes over 12 min. Pooled and concentrated desired fractions to afford, 0.23 g (78%) of the title compound as a yellow oil. LCMS m/z 469.3 (M+H)+. ret. time=2.29 min

Workup

  1. additionMixed more reagents for 15 min
  2. additionthen added to solution above and
  3. extractionextracted with DCM (3×25 ml)
  4. concentrationThe combined organics (liquids and solids) were concentrated
  5. customto afford a red semisolid
  6. extractionextracted with DCM (3×100 ml)
  7. dry with materialThe combined organics were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by flash chromatography
  11. washISCO 24 g eluting with 0% to 100% ethyl acetate in hexanes over 12 min
  12. concentrationPooled and concentrated desired fractions
  13. customto afford

Sources & evidence

ORD record
ord-43ef0a03688a40568264227ea03b26ca
Source dataset
uspto-grants-2015_04
Patent number
US09018395B2

Reaction notes

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