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

HRID 60513Notes

Reaction equation

HRID 60513 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][CH2:30][CH:31]([CH3:33])[CH3:32])=[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]([CH3:34])[C:8]1=[O:35])=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]([CH2:29][CH2:30][CH:31]([CH3:33])[CH3:32])=[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]([CH3:34])[C:8]1=[O:35]

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 1188758923-(5-isopentyl-1-methyl-2,4-dioxo-6-(3-(trifluoromethyl)phenoxy)-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate

Product 1

HCID 1188755373-(3-hydroxypropyl)-5-isopentyl-1-methyl-6-(3-(trifluoromethyl)phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dioneYield 46.5%

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-(trifluoromethyl)phenoxy)-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate (30 mg, 0.060 mmol) in THF (4 mL) and water (4 mL)) was added LiOH.H2O (5.10 mg, 0.12 mmol). The reaction was stirred at RT for 15 min then diluted with EA (5 mL) and water (5 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-(trifluoromethyl)phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (13 mg, 45.9% yield) as a white solid. 1H NMR (DMSO-d6) δ: 8.58 (s, 1H), 7.61 (t, J=7.8 Hz, 1H), 7.48 (d, J=7.6 Hz, 1H), 7.26 (d, J=8.6 Hz, 2H), 4.50 (t, J=5.2 Hz, 1H), 4.09-3.93 (m, 2H), 3.58 (s, 3H), 3.48 (q, J=6.3 Hz, 2H), 3.19-3.06 (m, 2H), 1.75 (dd, J=14.0, 6.8 Hz, 2H), 1.51 (dd, J=13.0, 6.6 Hz, 1H), 1.29 (dd, J=15.3, 7.2 Hz, 2H), 0.79 (d, J=6.6 Hz, 6H). LCMS: MH+ 466 and TR=3.373 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-84012e67a9ce4fcebc2d99274d34efa3
Source dataset
uspto-grants-2016_09
Patent number
US09440972B2

Reaction notes

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