Trifluoroacetic acid → 5-(5-Phenyl-4-((pyridin-2-ylmethyl)amino)phthalazin-1-yl)pyridine-3-sulfonamide

HRID 593696Notes

Reaction equation

HRID 593696 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][CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=3)=[N:17][N:16]=2)[CH:14]=1)(=[O:8])=[O:7])(C)(C)C.C(O)(C(F)(F)F)=O>>[C:25]1([C:20]2[CH:21]=[CH:22][CH:23]=[C:24]3[C:19]=2[C:18]([NH:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=2)=[N:17][N:16]=[C:15]3[C:13]2[CH:14]=[C:9]([S:6]([NH2:5])(=[O:7])=[O:8])[CH:10]=[N:11][CH:12]=2)[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 90423975N-(tert-butyl)-5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)phthalazin-1-yl)pyridine-3-sulfonamide

Product 1

HCID 862701075-(5-Phenyl-4-((pyridin-2-ylmethyl)amino)phthalazin-1-yl)pyridine-3-sulfonamideYield 37.4%

Procedure

N-(tert-Butyl)-5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)phthalazin-1-yl)pyridine-3-sulfonamide (0.0300 g, 0.0570 mmol) was dissolved in TFA (5.00 mL, 64.9 mmol) and stirred at room temperature for 12 h. TFA was removed under reduced pressure and reaction mixture was diluted with saturated NaHCO3 (50 mL). The reaction mixture was extracted with EtOAc (3×30 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 16 as described in general methods) to afford 5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)phthalazin-1-yl)pyridine-3-sulfonamide (10.0 mg, 37.3%) as a white solid. LCMS (Condition 4): retention time 2.25 min, [M+1]=469.2. HPLC (Condition 28): retention time=5.73 min, purity 99.07%. 1H NMR (400 MHz, CD3OD) δ 4.68 (s, 2 H), 7.24 (dd, J=4.8 Hz, J=7.6 Hz, 1 H), 7.27 (d, J=7.6 Hz, 1 H), 7.52 (br s, 5 H), 7.71-7.77 (m, 2 H), 7.88 (dd, J=1.6 Hz, J=8.4 Hz, 1 H), 7.95 (dd, J=7.2 Hz, J=8.4 Hz, 1 H), 8.30-8.31 (m, 1 H), 8.57 (dd, J=2.0 Hz, J=2.4 Hz, 1 H), 9.07 (d, J=2.0 Hz, 1 H), 9.21 (d, J=2.4 Hz, 1 H).

Workup

  1. customTFA was removed under reduced pressure and reaction mixture
  2. additionwas diluted with saturated NaHCO3 (50 mL)
  3. extractionThe reaction mixture was extracted with EtOAc (3×30 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 16 as described in general methods)

Sources & evidence

ORD record
ord-eb47001c2f474b309a55278bb832159b
Source dataset
uspto-grants-2016_01
Patent number
US09242966B2

Reaction notes

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