HCID 66883847, compound → HCID 178474855, compound

HRID 2402964Notes

Reaction equation

HRID 2402964 reaction equation
Cl.[F:2][C:3]1[CH:8]=[C:7]([N:9]2[CH2:13][C@H:12]([CH2:14][NH:15][C:16](=[O:18])[CH3:17])[O:11][C:10]2=[O:19])[CH:6]=[CH:5][C:4]=1[C:20]1[CH:25]=[CH:24][C:23]([CH2:26][NH:27][CH2:28][C:29]2[N:33](CC3C=CC(OC)=CC=3)[N:32]=[N:31][CH:30]=2)=[CH:22][CH:21]=1>FC(F)(F)C(O)=O>[F:2][C:3]1[CH:8]=[C:7]([N:9]2[CH2:13][C@H:12]([CH2:14][NH:15][C:16](=[O:18])[CH3:17])[O:11][C:10]2=[O:19])[CH:6]=[CH:5][C:4]=1[C:20]1[CH:25]=[CH:24][C:23]([CH2:26][NH:27][CH2:28][C:29]2[N:33]=[N:32][NH:31][CH:30]=2)=[CH:22][CH:21]=1

Participants

3

Reactant 1

HCID 66883847HCID 66883847, compound

Product 1

HCID 178474855HCID 178474855, compound

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
67.5 °C

Procedure

A solution of the crude regioisomeric mixture of (5S)—N-{3-[2-fluoro-4′-({[1-(4-methoxy-benzyl)-1H-[1,2,3]triazol-4-ylmethyl]-amino}-methyl)-biphenyl-4-yl]-2-oxo-oxazolidin-1-ylmethyl}-acetamide hydrochloride and (5S)—N-{3-[2-fluoro-4′-({[1-(4-methoxy-benzyl)-1H-[1,2,3]triazol-5-ylmethyl]-amino}-methyl)-biphenyl-4-yl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide hydrochloride (1013 and 1014, 29.17 g, 49.07 mmol) in trifluoroacetic acid (TFA, 150 mL) was warmed up to 65-70° C., and the resulting reaction mixture was stirred at 65-70° C. for 12 h. When TLC and HPLC/MS showed that the deprotection reaction was complete, the solvents were removed in vacuo. The residual solids were then treated with ethyl acetate (EtOAc, 100 mL) and H2O (150 mL) before being treated with a saturated aqueous solution of sodium carbonate (30 mL) at room temperature. The resulting mixture was then stirred at room temperature for 1 h before the solids were collected by filtration, washed with EtOAc (2×50 mL) and H2O (2×50 mL), and dried in vacuo at 40-45° C. to afford the crude, (5S)—N-[3-(2-fluoro-4′-{[(1H-[1,2,3]triazol-4-ylmethyl)-amino]-methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-ylmethyl]-acetamide (1 as the free base, 18.9 g, 21.49 g theoretical, 87.9%) as off-white powders, which by HPLC/MS and 1H NMR was found to be one pure regioisomer and this regioisomer was found to be identical as the material obtained from deprotection of 1013 alone by the same method. For 1 as the free base: 1H NMR (300 MHz, DMSO-d6) δ 1.85 (s, 3H, COCH3), 3.44 (t, 2H, J=5.4 Hz), 3.74 (s, 2H), 3.77 (s, 2H), 3.79 (dd, 1H, J=6.4, 9.2 Hz), 4.17 (t, 1H, J=9.1 Hz), 4.72-4.81 (m, 1H), 7.39-7.62 (m, 7H, aromatic-H), 7.73 (s, 1H, triazole-CH), 8.29 (t, 1H, J=5.8 Hz, NHCOCH3), 9.72 (br. s, 2H, ArCH2N+H2), 15.20 (br. s, 1H, triazole-NH); C22H23FN6O3, LCMS (EI) m/e 439 (M++H) and 461 (M++Na).

Workup

  1. customthe resulting reaction mixture
  2. customWhen TLC and HPLC/MS showed that the deprotection reaction
  3. customthe solvents were removed in vacuo
  4. additionThe residual solids were then treated with ethyl acetate (EtOAc, 100 mL) and H2O (150 mL)
  5. additionbefore being treated with a saturated aqueous solution of sodium carbonate (30 mL) at room temperature
  6. stirringThe resulting mixture was then stirred at room temperature for 1 h before the solids
  7. filtrationwere collected by filtration
  8. washwashed with EtOAc (2×50 mL) and H2O (2×50 mL)
  9. customdried in vacuo at 40-45° C.

Sources & evidence

ORD record
ord-d7e14ebb63ef4add914c572ac9dcf7ca
Source dataset
uspto-grants-2014_08
Patent number
US08796465B2

Reaction notes

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