Trifluoroacetic anhydride → 1-(5-Bromo-4-(4-trifluoromethylthiazol-2-yl)pyridin-2-yl)-3-ethylurea

HRID 2243061Notes

Reaction equation

HRID 2243061 reaction equation
[Br:1][C:2]1[C:3]([C:14]2[S:15][CH2:16][C:17](O)([C:19]([F:22])([F:21])[F:20])[N:18]=2)=[CH:4][C:5]([NH:8][C:9]([NH:11][CH2:12][CH3:13])=[O:10])=[N:6][CH:7]=1.C(OC(C(F)(F)F)=O)(C(F)(F)F)=O>C(Cl)Cl>[Br:1][C:2]1[C:3]([C:14]2[S:15][CH:16]=[C:17]([C:19]([F:21])([F:20])[F:22])[N:18]=2)=[CH:4][C:5]([NH:8][C:9]([NH:11][CH2:12][CH3:13])=[O:10])=[N:6][CH:7]=1

Participants

4

Reactant 2

HCID 9845Trifluoroacetic anhydride2×HCID 59208483AZD7118 Bromo Trifluoromethyl2×

Product 1

HCID 592083731-(5-Bromo-4-(4-trifluoromethylthiazol-2-yl)pyridin-2-yl)-3-ethylureaYield 24.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 1-(5-bromo-4-(4-hydroxy-4-(trifluoromethyl)-4,5-dihydrothiazol-2-yl)pyridin-2-yl)-3-ethylurea (Intermediate 41, 2.2 g, 5.32 mmol) in DCM (30 mL), TFAA (1.128 mL, 7.99 mmol) followed by TEA (1.113 mL, 7.99 mmol) were added. The reaction mixture was allowed to stir overnight at room temperature, then another 150 uL of TEA and TFAA were added and the reaction mixture was stirred for additional 3 h. The reaction was concentrated under reduced pressure, and the residue was partitioned between water and ethyl acetate. The layers were separated, and the organic layer was washed with sodium bicarbonate solution, water and brine, then dried over magnesium sulfate and concentrated under reduced pressure. The light yellow solid obtained was purified by normal phase (1% MeOH in dichloromethane to 3% MeOH in dichloromethane) to give 520 mg of the product. MS (ESP): 396 (M+1) for C12H10BrN3O; NMR: 1.07 (t, 3H); 3.11-3.17 (m, 2H); 7.24 (t, 1H); 8.35 (s, 1H); 8.50 (s, 1H); 8.77 (s, 1H); 9.34 (s, 1H)

Workup

  1. additionwere added
  2. stirringthe reaction mixture was stirred for additional 3 h
  3. concentrationThe reaction was concentrated under reduced pressure
  4. customthe residue was partitioned between water and ethyl acetate
  5. customThe layers were separated
  6. washthe organic layer was washed with sodium bicarbonate solution, water and brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe light yellow solid obtained
  10. customwas purified by normal phase (1% MeOH in dichloromethane to 3% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-d383ef7d10e343a2aa6d0c6c766a36ff
Source dataset
uspto-grants-2010_03
Patent number
US07674801B2

Reaction notes

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