Thiazole → HCID 89907235, compound

HRID 629068Notes

Reaction equation

HRID 629068 reaction equation
I[C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[CH3:22])[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]>[CH3:22][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 89907516HCID 89907516, compound

Product 1

HCID 89907235HCID 89907235, compound

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
130 °C

Procedure

3-Iodo-4-methyl-N-(4-(trifluoromethoxy)phenyl)benzamide (Stage 13.1, 100 mg, 0.237 mmol), thiazole (60 mg, 0.712 mmol), KOAc (69.9 mg, 0.712 mmol) and Pd(OAc)2 (0.267 mg, 1.187 μmol) were added to a vial, which was sealed, evacuated/purged with argon. DMA (720 μL) was added and the RM was stirred at 130° C. for 2.5 days. The RM was diluted with THF (3 mL), stirred overnight with Si-Thiol (1.44 mmol/g, 16.49 mg, 0.024 mmol) and filtered. The filtrate was treated with 2 M HCl (40 mL) and extracted with TBME. The combined extracts were washed with 1 M HCl, sat. NaHCO3, brine, dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give a residue which was purified by preparative SFC (Column NH2, from 10% to 15% in 2.4 min) to afford the title compound as a colorless solid. UPLC-MS (Condition 2) tR=1.18 min, m/z=379.2 [M+H]+, m/z=377.2 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 2.44 (s, 3H) 7.37 (d, J=8.31 Hz, 2H) 7.54 (d, J=8.07 Hz, 1H) 7.86-7.91 (m, 2H) 7.93 (dd, J=7.82, 1.96 Hz, 1H) 8.02 (d, J=1.96 Hz, 1H) 8.10 (d, J=0.73 Hz, 1H) 9.23 (d, J=0.73 Hz, 1H) 10.43 (s, 1H).

Workup

  1. customwas sealed
  2. customevacuated/purged with argon
  3. additionDMA (720 μL) was added
  4. additionThe RM was diluted with THF (3 mL)
  5. filtrationfiltered
  6. additionThe filtrate was treated with 2 M HCl (40 mL)
  7. extractionextracted with TBME
  8. washThe combined extracts were washed with 1 M HCl, sat. NaHCO3, brine
  9. dry with materialdried over Na2SO4
  10. customthe solvent was evaporated off under reduced pressure
  11. customto give a residue which
  12. customwas purified by preparative SFC (Column NH2, from 10% to 15% in 2.4 min)

Sources & evidence

ORD record
ord-329958cf6eed40aab96cba11ce4cd4b9
Source dataset
uspto-grants-2016_04
Patent number
US09315489B2

Reaction notes

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