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

HRID 60518Notes

Reaction equation

HRID 60518 reaction equation
C([O:3][CH2:4][CH2:5][CH2:6][N:7]1[C:12](=[O:13])[C:11]2[C:14]([CH2:30][CH2:31][CH:32]([CH3:34])[CH3:33])=[C:15]([O:18][C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([O:25][C:26]([F:29])([F:28])[F:27])[CH:20]=3)[CH:16]=[N:17][C:10]=2[N:9]([CH3:35])[C:8]1=[O:36])=O.O[Li].O>C1COCC1.O.CC(=O)OCC>[OH:3][CH2:4][CH2:5][CH2:6][N:7]1[C:12](=[O:13])[C:11]2[C:14]([CH2:30][CH2:31][CH:32]([CH3:34])[CH3:33])=[C:15]([O:18][C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([O:25][C:26]([F:29])([F:28])[F:27])[CH:20]=3)[CH:16]=[N:17][C:10]=2[N:9]([CH3:35])[C:8]1=[O:36]

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 118875887HCID 118875887, compound

Product 1

HCID 1188755033-(3-hydroxypropyl)-5-isopentyl-1-methyl-6-(3-(trifluoromethoxy)phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dioneYield 21.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-(5-isopentyl-1-methyl-2,4-dioxo-6-(3-(trifluoromethoxy)phenoxy)-1,2-dihydro pyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate (50 mg, 0.098 mmol) in THF (2 mL) and water (2 mL was added LiOH.H2O (8.2 mg, 0.196 mmol). The reaction was stirred at RT for 30 min then diluted with EA (10 mL) and water (10 mL). The organic layer was dried over Na2SO4 and concentrated to a residue which was purified by Prep HPLC to give 3-(3-hydroxypropyl)-5-isopentyl-1-methyl-6-(3-(trifluoromethoxy)phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (10 mg, 20.0% yield) as a white solid. 1H NMR (DMSO-d6) δ: 8.57 (s, 1H), 7.49 (t, J=8.8 Hz, 1H), 7.11 (d, J=8.0 Hz, 1H), 6.98-6.95 (m, 2H), 4.51 (t, J=5.6 Hz, 1H), 4.02-3.97 (m, 2H), 3.58 (s, 3H), 3.50-3.45 (m, 2H), 3.15-3.10 (m, 2H), 1.77-1.70 (m, 2H), 1.54-1.50 (m, 1H), 1.32-1.23 (m, 2H), 0.79 (d, J=6.8 Hz, 6H). LCMS: MH+ 482 and TR=3.447 min.

Workup

  1. dry with materialThe organic layer was dried over Na2SO4
  2. concentrationconcentrated to a residue which
  3. customwas purified by Prep HPLC

Sources & evidence

ORD record
ord-0b71b63b8f83467887cba5e849df33c2
Source dataset
uspto-grants-2016_09
Patent number
US09440972B2

Reaction notes

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