Trifluoroacetic acid → 5-(1-((3-Fluorophenyl)amino)-8-phenylpyrrolo[1,2-d][1,2,4]triazin-4-yl)pyridine-3-sulfonamide

HRID 1478405Notes

Reaction equation

HRID 1478405 reaction equation
C([NH:5][S:6]([C:9]1[CH:10]=[N:11][CH:12]=[C:13]([C:15]2[N:20]3[CH:21]=[CH:22][C:23]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[C:19]3[C:18]([NH:30][C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([F:37])[CH:32]=3)=[N:17][N:16]=2)[CH:14]=1)(=[O:8])=[O:7])(C)(C)C.C(O)(C(F)(F)F)=O>>[F:37][C:33]1[CH:32]=[C:31]([NH:30][C:18]2[C:19]3[N:20]([CH:21]=[CH:22][C:23]=3[C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[C:15]([C:13]3[CH:14]=[C:9]([S:6]([NH2:5])(=[O:8])=[O:7])[CH:10]=[N:11][CH:12]=3)=[N:16][N:17]=2)[CH:36]=[CH:35][CH:34]=1

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 90424234N-(tert-butyl)-5-(1-((3-fluorophenyl)amino)-8-phenylpyrrolo[1,2-d][1,2,4]triazin-4-yl)pyridine-3-sulfonamide

Product 1

HCID 862700195-(1-((3-Fluorophenyl)amino)-8-phenylpyrrolo[1,2-d][1,2,4]triazin-4-yl)pyridine-3-sulfonamideYield 56%

Conditions

Temperature
65 °C

Procedure

N-(tert-Butyl)-5-(1-((3-fluorophenyl)amino)-8-phenylpyrrolo[1,2-d][1,2,4]triazin-4-yl)pyridine-3-sulfonamide (0.020 g, 0.039 mmol) was dissolved in TFA (0.500 mL, 6.48 mmol) and heated at 65° C. for 4 h. TFA was removed under reduced pressure and the resulting residue was diluted with saturated NaHCO3 (10 mL). The reaction mixture was extracted with EtOAc (3×20 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give a residue which was purified by preparative HPLC (Condition B-9 described in general methods) to afford 5-(1-((3-fluorophenyl)amino)-8-phenylpyrrolo[1,2-d][1,2,4]triazin-4-yl)pyridine-3-sulfonamide (0.010 g, 56%) as a pale yellow solid. LCMS Method B-7: retention time 1.79 min, [M+1]=461.0, Purity 99.6%. LCMS Method B-8: retention time 1.30 min, [M+1]=461.0, Purity 100%. 1H NMR (400 MHz, DMSO-d6) δ ppm: 6.82 (td, J=2.0 Hz, J=8.4 Hz, 1H), 6.95 (dd, J=1.6 Hz, J=8.4 Hz, 1H), 7.12 (d, J=2.8 Hz, 1H), 7.27-7.33 (m, 1H), 7.50-7.65 (m, 6H), 7.71 (dt, J=2.4 Hz, J=12.0 Hz, 1H), 7.77 (br s, 2H), 7.81 (d, J=2.8 Hz, 1H), 8.70 (t, J=2.0 Hz, 1H), 9.20 (d, J=2.0 Hz, 1H), 9.31 (d, J=2.0 Hz, 1H).

Workup

  1. customTFA was removed under reduced pressure
  2. additionthe resulting residue was diluted with saturated NaHCO3 (10 mL)
  3. extractionThe reaction mixture was extracted with EtOAc (3×20 mL)
  4. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto give a residue which
  8. customwas purified by preparative HPLC (Condition B-9 described in general methods)

Sources & evidence

ORD record
ord-2ba4f78f10684d0da48e9578f131a3e6
Source dataset
uspto-grants-2016_08
Patent number
US09403834B2

Reaction notes

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