Trifluoroacetic acid → 4'-(5-Aminopyrazin-2-yl)-3'-fluoro-[1,1'-biphenyl]-2-sulfonamide

HRID 1523776Notes

Reaction equation

HRID 1523776 reaction equation
[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]3[C:15]([S:20]([NH:23]C(C)(C)C)(=[O:22])=[O:21])=[CH:16][CH:17]=[CH:18][CH:19]=3)=[CH:10][C:9]=2[F:28])=[N:6][CH:7]=1.C1(OC)C=CC=CC=1.C(O)(C(F)(F)F)=O>>[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]3[C:15]([S:20]([NH2:23])(=[O:22])=[O:21])=[CH:16][CH:17]=[CH:18][CH:19]=3)=[CH:10][C:9]=2[F:28])=[N:6][CH:7]=1

Participants

4

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 778446974'-(5-aminopyrazin-2-yl)-N-tert-butyl-3'-fluorobiphenyl-2-sulfonamide

Product 1

HCID 770506804'-(5-Aminopyrazin-2-yl)-3'-fluoro-[1,1'-biphenyl]-2-sulfonamideYield 72.4%

Procedure

A solution of 4′-(5-aminopyrazin-2-yl)-N-(tert-butyl)-3′-fluoro-[1,1′-biphenyl]-2-sulfonamide (130.0 g, 298.0 mmol), anisole (97.4 mL, 894.0 mmol), and TFA (228.0 mL, 2.98 mol) was stirred at 60° Celsius for 16 hours. The reaction was cooled to rt, concentrated to dryness, and partitioned between 600 mL H2O and 600 mL acetone. 750 mL sat. NaHCO3 (aq), was added over 30 min. The resulting precipitate was isolated via filtration and rinsed with 300 mL H2O then 300 mL acetone. The precipitate was triturated with 1.5 L acetone at 50° Celsius for 16 hours. After cooling to room temperature the solid was collected by filtration and rinsed twice with 250 mL acetone then dried in a vacuum oven at 50° Celsius for 16 hours yielding the title compound (74.3 g, 72.4%). MS (ESI): mass calcd. for C16H13FN4O2S, 344.07; m/z found, 345.1 [M+H]+. 1H NMR (600 MHz, DMSO-d6) δ 8.44-8.36 (s, 1H), 8.10-8.02 (m, 2H), 7.92-7.85 (m, 1H), 7.69-7.59 (m, 2H), 7.43-7.35 (m, 3H), 7.35-7.27 (m, 2H), 6.77-6.69 (s, 2H). Elemental analysis: calcd. for C16H13FN4O2S, C, 55.80; H, 3.81; N, 16.27; measured: C, 55.43; H, 3.54; N, 16.22.

Workup

  1. concentrationconcentrated to dryness
  2. custompartitioned between 600 mL H2O and 600 mL acetone
  3. addition750 mL sat. NaHCO3 (aq), was added over 30 min
  4. customThe resulting precipitate was isolated via filtration
  5. washrinsed with 300 mL H2O
  6. customThe precipitate was triturated with 1.5 L acetone at 50° Celsius for 16 hours
  7. temperatureAfter cooling to room temperature the solid
  8. filtrationwas collected by filtration
  9. washrinsed twice with 250 mL acetone
  10. customthen dried in a vacuum oven at 50° Celsius for 16 hours

Sources & evidence

ORD record
ord-f718bdbe717c45f589ec938e90b688d2
Source dataset
uspto-grants-2015_07
Patent number
US09079866B2

Reaction notes

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