Thiazole → 4-fluoro-3-(thiazol-5-yl)-N-(4-(trifluoromethoxy)phenyl)benzamide

HRID 525641Notes

Reaction equation

HRID 525641 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[F:22])[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]([F:18])([F:17])[F:16])=[CH:10][CH:9]=1)=[O:6].[S:23]1[CH:27]=[CH:26][N:25]=[CH:24]1.CC([O-])=O.[K+]>CC([O-])=O.CC([O-])=O.[Pd+2]>[F:22][C:21]1[CH:20]=[CH:19][C:4]([C:5]([NH:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]([F:18])([F:17])[F:16])=[CH:10][CH:9]=2)=[O:6])=[CH:3][C:2]=1[C:27]1[S:23][CH:24]=[N:25][CH:26]=1

Participants

5

Reactant 3

HCID 9256ThiazoleHCID 517044Potassium AcetateHCID 867025923-bromo-4-fluoro-N-(4-(trifluoromethoxy)phenyl)benzamide

Product 1

HCID 899067714-fluoro-3-(thiazol-5-yl)-N-(4-(trifluoromethoxy)phenyl)benzamide

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
130 °C

Procedure

A mixture of 3-bromo-4-fluoro-N-(4-(trifluoromethoxy)phenyl)benzamide (Stage 1.2, 100 mg, 0.264 mmol), thiazole (113 mg, 1.322 mmol), KOAc (130 mg, 1.322 mmol) and Pd(OAc)2 (0.297 mg, 1.322 μmol) were added to a vial, which was sealed and evacuated/purged with argon. DMA (0.81 mL) was added and the mixture was stirred at 130° C. for 20 h. The RM was diluted with THF (3 mL), treated with Si-Thiol (Silicycle, 1.44 mmol/g, 9.18 mg, 0.013 mmol) and filtered off. The filtrate was poured onto 1 M HCl (40 mL) and extracted 3 times with TBME. The combined extracts were washed 3 times with 1M HCl, sat. NaHCO3 and brine, dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give a crude product which was purified by flash chromatography (RediSep® Silica gel column, 4 g, cyclohexane/EtOAc from 10% to 40% EtOAc) to yield the title compound as an off-white solid. UPLC-MS (Condition 1) tR=2.80 min, m/z=383.0 [M+H]+, m/z=381.0 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 7.40 (m, J=8.31 Hz, 2H) 7.58 (dd, J=10.76, 8.80 Hz, 1H) 7.83-7.97 (m, 2H) 8.02 (ddd, J=8.62, 4.95, 2.32 Hz, 1H) 8.40 (dd, J=7.21, 2.32 Hz, 1H) 8.49 (s, 1H) 9.28 (s, 1H) 10.54 (s, 1H).

Workup

  1. additionwere added to a vial, which
  2. customwas sealed
  3. customevacuated/purged with argon
  4. additionDMA (0.81 mL) was added
  5. additionThe RM was diluted with THF (3 mL)
  6. filtrationfiltered off
  7. additionThe filtrate was poured onto 1 M HCl (40 mL)
  8. extractionextracted 3 times with TBME
  9. washThe combined extracts were washed 3 times with 1M HCl, sat. NaHCO3 and brine
  10. dry with materialdried over Na2SO4
  11. customthe solvent was evaporated off under reduced pressure
  12. customto give a crude product which
  13. customwas purified by flash chromatography (RediSep® Silica gel column, 4 g, cyclohexane/EtOAc from 10% to 40% EtOAc)

Sources & evidence

ORD record
ord-24650d99173e42c7bf57ba84c74a5d82
Source dataset
uspto-grants-2016_05
Patent number
US09340537B2

Reaction notes

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