Trifluoroacetic acid → 2-(Difluoromethyl)-5-(8-phenyl-1-((pyridin-2-ylmethyl)amino)pyrrolo[1,2-d][1,2,4]triazin-4-yl)pyridine-3-sulfonamide

HRID 1478410Notes

Reaction equation

HRID 1478410 reaction equation
C([NH:5][S:6]([C:9]1[C:10]([CH:38]([F:40])[F:39])=[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][CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][N: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:40][CH:38]([F:39])[C:10]1[C:9]([S:6]([NH2:5])(=[O:7])=[O:8])=[CH:14][C:13]([C:15]2[N:20]3[CH:21]=[CH:22][C:23]([C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=4)=[C:19]3[C:18]([NH:30][CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=3)=[N:17][N:16]=2)=[CH:12][N:11]=1

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 90425044N-(tert-butyl)-2-(difluoromethyl)-5-(8-phenyl-1-((pyridin-2-ylmethyl)amino)pyrrolo[1,2-d][1,2,4]triazin-4-yl)pyridine-3-sulfonamide

Product 1

HCID 862700202-(Difluoromethyl)-5-(8-phenyl-1-((pyridin-2-ylmethyl)amino)pyrrolo[1,2-d][1,2,4]triazin-4-yl)pyridine-3-sulfonamideYield 12.7%

Procedure

N-(tert-Butyl)-2-(difluoromethyl)-5-(8-phenyl-1-((pyridin-2-ylmethyl)amino)pyrrolo[1,2-d][1,2,4]triazin-4-yl)pyridine-3-sulfonamide (0.035 g, 0.062 mmol) was dissolved in TFA (2.00 mL, 26.0 mmol) and stirred at room temperature for 4 h. TFA was removed under reduced pressure and reaction mixture 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. The resulting residue was purified by preparative HPLC (Condition B-13 described in general methods) to afford 2-(difluoromethyl)-5-(8-phenyl-1-((pyridin-2-ylmethyl)amino)pyrrolo[1,2-d][1,2,4]triazin-4-yl)pyridine-3-sulfonamide (0.004 g, 10%) as a pale yellow solid. LCMS Method B-7: retention time 1.55 min, [M+1]=508.0, Purity 99.3%. LCMS Method B-8: retention time 1.14 min, [M+1]=508.0, Purity 99.3%. 1H NMR (400 MHz, CD3OD) δ ppm: 4.77 (s, 2H), 6.96 (d, J=2.8 Hz, 1H), 7.26-7.29 (m, 1H), 7.40 (d, J=7.6 Hz, 1H), 7.51-7.66 (m, 6H), 7.70 (d, J=2.8 Hz, 1H), 7.75-7.79 (m, 1H), 8.34 (br d, J=5.2 Hz, 1H), 8.89 (dd, J=0.8 Hz, 1.2 Hz, 1H), 9.35 (d, J=2.0 Hz, 1H).

Workup

  1. customTFA was removed under reduced pressure and reaction mixture
  2. additionwas 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. customThe resulting residue was purified by preparative HPLC (Condition B-13 described in general methods)

Sources & evidence

ORD record
ord-d5051c81bd49494b8c38dc36735cb021
Source dataset
uspto-grants-2016_08
Patent number
US09403834B2

Reaction notes

Loading…