Trifluoroacetic acid → N-(2,3-dihydroxypropyl)-5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)phthalazin-1-yl)nicotinamide

HRID 593708Notes

Reaction equation

HRID 593708 reaction equation
CC1(C)[O:6][CH:5]([CH2:7][NH:8][C:9](=[O:40])[C:10]2[CH:15]=[C:14]([C:16]3[C:25]4[C:20](=[C:21]([C:26]5[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=5)[CH:22]=[CH:23][CH:24]=4)[C:19]([NH:32][CH2:33][C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][N:35]=4)=[N:18][N:17]=3)[CH:13]=[N:12][CH:11]=2)[CH2:4][O:3]1.C(O)(C(F)(F)F)=O>>[OH:6][CH:5]([CH2:4][OH:3])[CH2:7][NH:8][C:9](=[O:40])[C:10]1[CH:15]=[C:14]([C:16]2[C:25]3[C:20](=[C:21]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[CH:22]=[CH:23][CH:24]=3)[C:19]([NH:32][CH2:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][N:35]=3)=[N:18][N:17]=2)[CH:13]=[N:12][CH:11]=1

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86270294N-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-5-(5-phenyl-4-((pyridin-2ylmethyl)amino)phthalazin-1-yl)nicotinamide

Product 1

HCID 90423672N-(2,3-dihydroxypropyl)-5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)phthalazin-1-yl)nicotinamideYield 65%

Conditions

Temperature
50 °C

Procedure

To N-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-5-(5-phenyl-4-((pyridin-2ylmethyl)amino)phthalazin-1-yl)nicotinamide (0.0200 g, 0.0370 mmol) was added TFA (0.00282 mL, 0.0370 mmol) at room temperature and was heated at 50° C. for 4 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 14 as described in general methods) to afford N-(2,3-dihydroxypropyl)-5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)phthalazin-1-yl)nicotinamide (0.0120 g, 65%). LCMS (Condition 7): retention time 1.59 min, [M+1]=507.2. HPLC (Condition 25): retention time 5.23 min, Purity 97.90%. 1H NMR (400 MHz, DMSO-d6) δ 3.21-3.49 (m, 4 H), 3.63-3.72 (m, 1 H), 4.55-4.60 (m, 1 H), 4.66 (d, J=4.0 Hz, 2 H), 4.84 (br s, 1 H), 6.32 (dd, J=4.0 Hz, J=4.4 Hz, 1 H), 7.22 (dd, J=4.8 Hz, J=6.8 Hz, 1 H), 7.28 (d, J=8.0 Hz, 1 H), 7.50-7.58 (m, 5 H), 7.68-7.73 (m, 2 H), 7.80 (dd, J=1.6 Hz, J=8.4 Hz, 1 H), 7.93 (dd, J=7.2 Hz, J=8.4 Hz, 1 H), 8.23 (d, J=4.8 Hz, 1 H), 8.51 (t, J=2.0 Hz, 1 H), 8.75 (t, J=5.6 Hz, 1 H), 8.98 (d, J=2.0 Hz, 1 H), 9.16 (d, J=2.0 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 14 as described in general methods)

Sources & evidence

ORD record
ord-00581da53cc247518851e6cdd8e42875
Source dataset
uspto-grants-2016_01
Patent number
US09242966B2

Reaction notes

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