Trifluoroacetic acid → 5-(4-((3-Fluorophenyl)amino)-5-phenylphthalazin-1-yl)pyridine-3-sulfonamide

HRID 593720Notes

Reaction equation

HRID 593720 reaction equation
C([NH:5][S:6]([C:9]1[CH:10]=[N:11][CH:12]=[C:13]([C:15]2[C:24]3[C:19](=[C:20]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH:21]=[CH:22][CH:23]=3)[C:18]([NH:31][C:32]3[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[CH:33]=3)=[N:17][N:16]=2)[CH:14]=1)(=[O:8])=[O:7])(C)(C)C.C(O)(C(F)(F)F)=O>>[F:38][C:34]1[CH:33]=[C:32]([NH:31][C:18]2[C:19]3[C:24](=[CH:23][CH:22]=[CH:21][C:20]=3[C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:15]([C:13]3[CH:14]=[C:9]([S:6]([NH2:5])(=[O:7])=[O:8])[CH:10]=[N:11][CH:12]=3)=[N:16][N:17]=2)[CH:37]=[CH:36][CH:35]=1

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 90424675N-(tert-butyl)-5-(4-((3-fluorophenyl)amino)-5-phenylphthalazin-1-yl)pyridine-3-sulfonamide

Product 1

HCID 904247755-(4-((3-Fluorophenyl)amino)-5-phenylphthalazin-1-yl)pyridine-3-sulfonamideYield 27.9%

Conditions

Temperature
65 °C

Procedure

N-(tert-Butyl)-5-(4-((3-fluorophenyl)amino)-5-phenylphthalazin-1-yl)pyridine-3-sulfonamide (0.600 g, 1.14 mmol) was dissolved in TFA (10.0 mL, 130 mmol) and heated to 65° C. for 4 h. TFA was removed under reduced pressure and the resulting residue was diluted with saturated NaHCO3 (100 mL). The reaction mixture was extracted with EtOAc (3×100 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The resulting residue was purified by combiflash (REDISEP®, silica gel, 40 g, 0-6% MeOH/DCM) to afford 5-(4-((3-fluorophenyl)amino)-5-phenylphthalazin-1-yl)pyridine-3-sulfonamide (0.15 g, 27%) as an off-white solid. LCMS (Condition 38): retention time 2.12 min, [M+1]=472.2. HPLC (Condition 25): retention time=9.61 min, purity 99.78%. 1H NMR (400 MHz, DMSO-d6) δ 6.50 (dd, J=1.6 Hz, J=8.0 Hz, 1 H), 6.76 (td, J=2.0 Hz, J=8.4 Hz, 1 H), 7.19-7.25 (m, 2 H), 7.53-7.66 (m, 6 H), 7.76 (br s, 2 H), 7.90 (dd, J=1.2 Hz, J=7.2 Hz, 1 H), 7.95 (dd, J=1.2 Hz, J=8.0 Hz, 1 H), 8.05 (dd, J=7.2 Hz, J=8.0 Hz, 1 H), 8.54 (dd, J=2.0 Hz, J=2.4 Hz, 1 H), 9.15 (d, J=2.0 Hz, 1 H), 9.16 (d, J=2.4 Hz, 1 H).

Workup

  1. customTFA was removed under reduced pressure
  2. additionthe resulting residue was diluted with saturated NaHCO3 (100 mL)
  3. extractionThe reaction mixture was extracted with EtOAc (3×100 mL)
  4. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by combiflash (REDISEP®, silica gel, 40 g, 0-6% MeOH/DCM)

Sources & evidence

ORD record
ord-0828320fd7a24869b856bff223bbd70e
Source dataset
uspto-grants-2016_01
Patent number
US09242966B2

Reaction notes

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