2,4,6-Trimethylpyridine → HCID 59559902, compound

HRID 1177250Notes

Reaction equation

HRID 1177250 reaction equation
[CH3:1][N:2]1[CH:6]=[CH:5][C:4]([NH:7][C:8]([C:10]2[CH:21]=[C:20]([O:22][C:23]3[CH:28]=[CH:27][C:26]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:25][CH:24]=3)[C:13]3[CH2:14][C:15]([CH2:18]O)([CH3:17])[O:16][C:12]=3[CH:11]=2)=[O:9])=[N:3]1.N1C(C)=CC(C)=CC=1C.[F:42]C(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O>C(Cl)Cl>[CH3:1][N:2]1[CH:6]=[CH:5][C:4]([NH:7][C:8]([C:10]2[CH:21]=[C:20]([O:22][C:23]3[CH:28]=[CH:27][C:26]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:25][CH:24]=3)[C:13]3[CH2:14][C:15]([CH2:18][F:42])([CH3:17])[O:16][C:12]=3[CH:11]=2)=[O:9])=[N:3]1

Participants

5

Reactant 3

HCID 79532,4,6-TrimethylpyridineHCID 67749Trifluoromethanesulfonic anhydrideHCID 59560330HCID 59560330, compound

Product 1

HCID 59559902HCID 59559902, compoundYield 28%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-hydroxymethyl-4-(4-methanesulfonyl-phenoxy)-2-methyl-2,3-dihydro-benzofuran-6-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide (227) (62 mg, 0.140 mmol) and 2,4,6-collidine (0.0359 mL, 0.271 mmol) in dry CH2Cl2 was added trifluoromethanesulfonic acid anhydride (0.0365 mL, 0.217 mmol) at 0° C. The mixture was stirred at 0° C. to room temperature for 1 hr. TLC indicated that the reaction was complete. The reaction was quenched with 0.5 N aqueous HCl, extracted with 3×CHCl3, dried over Na2SO4, and concentrated. The residue was dissolved in anhydrous CH2Cl2 (3 mL), and TBAF (1 mL, 1 M in THF) was added. The resulting mixture was stirred at room temperature for 1.5 hr, quenched with H2O, and extracted with 3×CHCl3. The combined organic layer was dried over Na2SO4, concentrated, and purified by column chromatography eluting with 50-65% EtOAc in hexanes to give a white solid (18 mg, 28% yield). 1H NMR (400 MHz, CDCl3) δ 8.55 (s, 1 H) 7.84-7.96 (m, 2 H) 7.25-7.31 (m, 2 H) 7.02-7.15 (m, 3 H) 6.72-6.83 (m, 1 H) 4.26-4.54 (m, 2 H) 3.79 (s, 3 H) 3.20 (d, J=16.67 Hz, 1 H) 3.08 (s, 3 H) 2.89 (dd, J=16.67, 1.77 Hz, 1 H) 1.52 (s, 3 H); LCMS for C22H22FN3O5S m/z 460.00 (M+H+).

Workup

  1. customThe reaction was quenched with 0.5 N aqueous HCl
  2. extractionextracted with 3×CHCl3
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in anhydrous CH2Cl2 (3 mL)
  6. additionTBAF (1 mL, 1 M in THF) was added
  7. stirringThe resulting mixture was stirred at room temperature for 1.5 hr
  8. customquenched with H2O
  9. extractionextracted with 3×CHCl3
  10. dry with materialThe combined organic layer was dried over Na2SO4
  11. concentrationconcentrated
  12. custompurified by column chromatography
  13. washeluting with 50-65% EtOAc in hexanes

Sources & evidence

ORD record
ord-bf81342d6b9846b085da0cdbfab89d74
Source dataset
uspto-grants-2010_11
Patent number
US07842713B2

Reaction notes

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