Triethylamine → Ethyl 3-(dimethylamino)-2-(5-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-2-fluorobenzoyl)acrylate

HRID 2061882Notes

Reaction equation

HRID 2061882 reaction equation
[CH2:1]([NH:3][C:4](=[O:31])[NH:5][C:6]1[N:11]=[CH:10][C:9]([C:12]2[CH:13]=[CH:14][C:15]([F:21])=[C:16]([CH:20]=2)[C:17](O)=[O:18])=[C:8]([C:22]2[S:23][CH:24]=[C:25]([C:27]([F:30])([F:29])[F:28])[N:26]=2)[CH:7]=1)[CH3:2].S(Cl)(Cl)=O.[CH3:36][N:37]([CH3:45])[CH:38]=[CH:39][C:40]([O:42][CH2:43][CH3:44])=[O:41].C(N(CC)CC)C.C([O-])(=O)C=C>C1(C)C=CC=CC=1.CN(C=O)C.C1COCC1.CCOC(C)=O.O>[CH3:36][N:37]([CH3:45])[CH:38]=[C:39]([C:17](=[O:18])[C:16]1[CH:20]=[C:12]([C:9]2[CH:10]=[N:11][C:6]([NH:5][C:4]([NH:3][CH2:1][CH3:2])=[O:31])=[CH:7][C:8]=2[C:22]2[S:23][CH:24]=[C:25]([C:27]([F:30])([F:28])[F:29])[N:26]=2)[CH:13]=[CH:14][C:15]=1[F:21])[C:40]([O:42][CH2:43][CH3:44])=[O:41]

Participants

11

Reactant 5

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 25188AcrylateHCID 121015Ethyl 3-(N,N-dimethylamino)acrylateHCID 59415756HCID 59415756, compound2×

Product 1

HCID 67028768Ethyl 3-(dimethylamino)-2-(5-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-2-fluorobenzoyl)acrylate

Reagents, catalysts & solvents 5

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
45 °C

Procedure

5-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-2-fluorobenzoic acid (0.180 g, 0.40 mmol, Intermediate 124) was suspended in toluene (3 mL). Thionyl chloride (0.145 mL, 1.98 mmol, Aldrich) and 1drop of DMF were added and the mixture was heated to 45° C. for 15 min After cooling to room temperature, the mixture was concentrated in vacuo, and toluene was added, then the mixture was concentrated in vacuo again to give a dark yellow residue. After drying under high vacuum overnight the oil turned into a dark yellow film. This film was taken up in THF (2 mL). In separate flask ethyl 3-(dimethylamino)acrylate (0.074 g, 0.51 mmol, Acros) and triethylamine (0.082 mL, 0.59 mmol, Acros) were dissolved in THF (5 ml). The solution of the acid chloride in THF (2 ml) was added dropwise to acrylate solution, then the flask was placed in an oil bath preheated to 72° C. and stirred for 1 h. After cooling to room temperature, the mixture was diluted with EtOAc(10 mL) and water (10 mL). The layers were separated and the organic layer was washed with 1 N HCl, twice with water, once with brine, then dry over Na2SO4, filter and concentrated in vacuo to give crude product as an orange oil.

Workup

  1. temperatureAfter cooling to room temperature
  2. concentrationthe mixture was concentrated in vacuo, and toluene
  3. additionwas added
  4. concentrationthe mixture was concentrated in vacuo again
  5. customto give a dark yellow residue
  6. customAfter drying under high vacuum overnight the oil
  7. customthe flask was placed in an oil bath
  8. custompreheated to 72° C.
  9. temperatureAfter cooling to room temperature
  10. customThe layers were separated
  11. washthe organic layer was washed with 1 N HCl, twice with water, once with brine
  12. dry with materialdry over Na2SO4
  13. filtrationfilter
  14. concentrationconcentrated in vacuo
  15. customto give crude product as an orange oil

Sources & evidence

ORD record
ord-bd68b9961cca4d2c83bbe6c535014e85
Source dataset
uspto-grants-2012_10
Patent number
US08283361B2

Reaction notes

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