Triethylamine → HCID 178495795, compound

HRID 78435Notes

Reaction equation

HRID 78435 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][N:5]1[C:9]([CH3:10])=[C:8]([CH3:11])[S:7][C:6]1=[NH:12].CCN(CC)CC.[F:20][C:21]1([F:33])[O:25][C:24]2[CH:26]=[CH:27][CH:28]=[C:29]([C:30](Cl)=[O:31])[C:23]=2[O:22]1>C1COCC1.CCOC(C)=O>[F:33][C:21]1([F:20])[O:25][C:24]2[CH:26]=[CH:27][CH:28]=[C:29]([C:30](/[N:12]=[C:6]3\[S:7][C:8]([CH3:11])=[C:9]([CH3:10])[N:5]\3[CH2:4][CH2:3][O:2][CH3:1])=[O:31])[C:23]=2[O:22]1

Participants

6

Reactant 3

HCID 8471Triethylamine2×HCID 27740622,2-Difluoro-1,3-benzodioxole-4-carbonyl chloride2×HCID 668517233-(2-Methoxy-ethyl)-4,5-dimethyl-3H-thiazol-2-ylideneamine

Product 1

HCID 178495795HCID 178495795, compoundYield 55%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To the product of Example 126A (0.20 g, 1.1 mmol) in 30 mL THF was added Et3N (0.37 mL, 2.7 mmol) followed by 2,2-difluoro-1,3-benzodioxole-4-carbonyl chloride (Lancaster, 0.29 g, 1.3 mmol). This mixture was stirred at ambient temperature for 17 hours then was warmed to reflux and allowed to stir for an additional 4 hours. The mixture was then cooled to ambient temperature and additional 2,2-difluoro-1,3-benzodioxole-4-carbonyl chloride (73 mg, 0.33 mmol) and Et3N (0.37 mL, 2.7 mmol) were added. This mixture was warmed to reflux at which temperature it stirred for 2 hours. The mixture was then cooled to ambient temperature, diluted with 10 mL EtOAc and washed with 5 mL saturated, aqueous NH4Cl. The layers were separated and the aqueous layer was extracted 2×5 mL EtOAc. The combined organics were dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure and purified via flash column chromatography (SiO2, 50% hexanes:EtOAc) to afford the title compound (0.22 g, 0.59 mmol, 55% yield). 1H NMR (300 MHz, CDCl3) δ ppm 2.26 (s, 3H), 2.28 (s, 3H), 3.32 (s, 3H), 3.83 (t, J=5.1 Hz, 2H), 4.44 (t, J=5.1 Hz, 2H), 7.12 (d, J=4.4 Hz, 1H), 7.14 (s, 1H), 7.89 (dd, J=6.6, 2.9 Hz, 1H); MS (DCI/NH3) m/z 371 (M+H)+; Anal. calculated for C16H16F2N2O4S: C, 51.89; H, 4.35; N, 7.56. Found: C, 52.27; H, 4.24; N, 7.53.

Workup

  1. temperaturethen was warmed
  2. temperatureto reflux
  3. stirringto stir for an additional 4 hours
  4. temperatureThe mixture was then cooled to ambient temperature
  5. temperatureThis mixture was warmed
  6. temperatureto reflux at which temperature it
  7. stirringstirred for 2 hours
  8. temperatureThe mixture was then cooled to ambient temperature
  9. washwashed with 5 mL saturated
  10. customThe layers were separated
  11. extractionthe aqueous layer was extracted 2×5 mL EtOAc
  12. dry with materialThe combined organics were dried over anhydrous Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure
  15. custompurified via flash column chromatography (SiO2, 50% hexanes:EtOAc)

Sources & evidence

ORD record
ord-088036f5e8114609ab2b1d0268e977af
Source dataset
uspto-grants-2014_09
Patent number
US08841334B2

Reaction notes

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