Acetyl chloride → HCID 24992764, compound

HRID 1673224Notes

Reaction equation

HRID 1673224 reaction equation
[Cl:1]C1C=CC(C2C=C3C(C(O)=O)CC(C)(C)OC3=NC=2C2C=CC(Cl)=CC=2Cl)=CC=1.[Cl:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=1[C:38]1[N:43]=[C:42]2[O:44][C:45]([CH3:52])([CH3:51])[CH2:46][CH:47]([C:48](O)=[O:49])[C:41]2=[CH:40][C:39]=1[C:53]1[CH:58]=[CH:57][C:56]([Cl:59])=[CH:55][CH:54]=1.O[N:61]1[C:65]2[CH:66]=CC=CC=2N=[N:62]1.O.NN.C(Cl)(=O)C>CC#N.CCOC(C)=O>[Cl:59][C:56]1[CH:57]=[CH:58][C:53]([C:39]2[CH:40]=[C:41]3[CH:47]([C:48]4[O:49][C:65]([CH3:66])=[N:61][N:62]=4)[CH2:46][C:45]([CH3:51])([CH3:52])[O:44][C:42]3=[N:43][C:38]=2[C:33]2[CH:34]=[CH:35][C:36]([Cl:1])=[CH:37][C:32]=2[Cl:31])=[CH:54][CH:55]=1

Participants

8

Reactant 5

HCID 6367Acetyl chlorideHCID 24654Hydrazine hydrate (1:1)HCID 757711-HydroxybenzotriazoleHCID 67020010HCID 67020010, compoundHCID 67020061HCID 67020061, compound

Product 1

HCID 24992764HCID 24992764, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To 6-(4-chlorophenyl)-7-(2,4-dichlorophenyl)-2,2-dimethyl-3,4-dihydro-2H-pyrano[2,3-b]pyridine-4-carboxylic acid prepared in similar fashion to the product of Example 124 Step B (20 mg, 0.05 mmol) in MeCN (1 mL) was added 1-hydroxybenzotriazole (HOBt) (7 mg, 0.005 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarboddimide hydrochloride (EDAC) (10 mg, 0.05 mmol) and the reaction was stirred at rt for 30 min. The reaction was cooled to 0° C. and hydrazine hydrate (0.005 mL, 0.09 mmol) was added and the reaction was stirred for 5 min. EtOAc was added and the organic portion was washed with saturated aq NaHCO3 and water, dried (Na2SO4), filtered and concentrated. The residue was dissolved in CH2Cl2 (2 mL). Acetyl chloride (0.025 mL, 0.35 mmol) was added and the reaction was stirred 10 min. EtOAc was added and the solution was washed with saturated aq NaHCO3, dried (Na2SO4), filtered and concentrated. The residue was dissolved in toluene (0.5 mL) and POCl3 (0.2 mL) was added. The reaction was refluxed overnight, diluted with CH2Cl2, washed with a saturated aq solution of NaHCO3, dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography on silica gel gradient eluted with 0-50% EtOAc in hexane to afford the title compound. (LC-2) HPLC/MS: 500.2 (M+1), 502.2 (M+3); Rt=3.91 min.

Workup

  1. temperatureThe reaction was cooled to 0° C.
  2. stirringthe reaction was stirred for 5 min
  3. washthe organic portion was washed with saturated aq NaHCO3 and water
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in CH2Cl2 (2 mL)
  8. stirringthe reaction was stirred 10 min
  9. washthe solution was washed with saturated aq NaHCO3
  10. dry with materialdried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. dissolutionThe residue was dissolved in toluene (0.5 mL)
  14. additionPOCl3 (0.2 mL) was added
  15. temperatureThe reaction was refluxed overnight
  16. additiondiluted with CH2Cl2
  17. washwashed with a saturated aq solution of NaHCO3
  18. dry with materialdried (Na2SO4)
  19. filtrationfiltered
  20. concentrationconcentrated
  21. customThe residue was purified by flash chromatography on silica gel gradient
  22. washeluted with 0-50% EtOAc in hexane

Sources & evidence

ORD record
ord-4ee369f8c19c407393b72b5c734ac87c
Source dataset
uspto-grants-2011_08
Patent number
US07999107B2

Reaction notes

Loading…