Lithium hydroxide, monohydrate → 3-(3-hydroxypropyl)-1-methyl-5-(4-(trifluoromethyl)benzyl)-6-(3-(trifluoromethyl)phenoxy)pyrido[2,3-d]pyrimidine-2,4 (1H,3H)-dione

HRID 60452Notes

Reaction equation

HRID 60452 reaction equation
C([O:3][CH2:4][CH2:5][CH2:6][N:7]1[C:12](=[O:13])[C:11]2[C:14]([CH2:29][C:30]3[CH:35]=[CH:34][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:32][CH:31]=3)=[C:15]([O:18][C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=3)[CH:16]=[N:17][C:10]=2[N:9]([CH3:40])[C:8]1=[O:41])=O.O[Li].O>C1COCC1>[OH:3][CH2:4][CH2:5][CH2:6][N:7]1[C:12](=[O:13])[C:11]2[C:14]([CH2:29][C:30]3[CH:31]=[CH:32][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:34][CH:35]=3)=[C:15]([O:18][C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:26])([F:27])[F:28])[CH:20]=3)[CH:16]=[N:17][C:10]=2[N:9]([CH3:40])[C:8]1=[O:41]

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 1188758823-(1-methyl-2,4-dioxo-5-(4-(trifluoromethyl)benzyl)-6-(3-(trifluoromethyl) phenoxy)-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate

Product 1

HCID 1188755293-(3-hydroxypropyl)-1-methyl-5-(4-(trifluoromethyl)benzyl)-6-(3-(trifluoromethyl)phenoxy)pyrido[2,3-d]pyrimidine-2,4 (1H,3H)-dioneYield 14%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-(1-methyl-2,4-dioxo-5-(4-(trifluoromethyl)benzyl)-6-(3-(trifluoromethyl) phenoxy)-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate (150 mg, 0.258 mmol) in THF (2 mL) was added aq. LiOH.H2O (1 mL, 0.5 M). The reaction was stirred at RT for 10 min then extracted with EA (50 mL). The organic layer was washed with brine (10 mL), dried over Na2SO4 and concentrated to a residue which was purified by Prep HPLC to give 3-(3-hydroxypropyl)-1-methyl-5-(4-(trifluoromethyl)benzyl)-6-(3-(trifluoromethyl)phenoxy)pyrido[2,3-d]pyrimidine-2,4 (1H,3H)-dione (20 mg, 8% yield over 3 steps) as a white solid. 1H NMR (CDCl3) δ: 8.37 (s, 1H), 7.42 (m, 3H), 7.35 (m, 1H), 7.31 (m, 2H), 7.02 (m, 2H), 4.83 (s, 2H), 4.24 (t, J=6.1 Hz, 2H), 3.73 (s, 3H), 3.56 (s, 2H), 2.95 (s, 1H), 1.98-1.87 (m, 2H). LCMS: MH+ 554 and TR=3.39 min.

Workup

  1. extractionthen extracted with EA (50 mL)
  2. washThe organic layer was washed with brine (10 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated to a residue which
  5. customwas purified by Prep HPLC

Sources & evidence

ORD record
ord-05aaefa147b64e8988c354f2b1bee315
Source dataset
uspto-grants-2016_09
Patent number
US09440972B2

Reaction notes

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