Lithium hydroxide, monohydrate → 6-(4-chlorophenoxy)-5-(4-fluorobenzyl)-3-(3-hydroxypropyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

HRID 60475Notes

Reaction equation

HRID 60475 reaction equation
C([O:3][CH2:4][CH2:5][CH2:6][N:7]1[C:12](=[O:13])[C:11]2[C:14]([CH2:26][C:27]3[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=3)=[C:15]([O:18][C:19]3[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][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>[Cl:25][C:22]1[CH:21]=[CH:20][C:19]([O:18][C:15]2[CH:16]=[N:17][C:10]3[N:9]([CH3:34])[C:8](=[O:35])[N:7]([CH2:6][CH2:5][CH2:4][OH:3])[C:12](=[O:13])[C:11]=3[C:14]=2[CH2:26][C:27]2[CH:28]=[CH:29][C:30]([F:33])=[CH:31][CH:32]=2)=[CH:24][CH:23]=1

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 118875899HCID 118875899, compound

Product 1

HCID 1188755426-(4-chlorophenoxy)-5-(4-fluorobenzyl)-3-(3-hydroxypropyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dioneYield 42.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-(6-(4-chlorophenoxy)-5-(4-fluorobenzyl)-1-methyl-2,4-dioxo-1,2-dihydro pyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate (50 mg, 0.10 mmol) in THF (3 mL) and water (3 mL) was added LiOH.H2O (10 mg, 0.20 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 6-(4-chlorophenoxy)-5-(4-fluorobenzyl)-3-(3-hydroxypropyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (20 mg, 37% yield) as a white solid. 1H NMR (CDCl3) δ: 8.31 (s, 1H), 7.31-7.27 (m, 2H), 7.22 (dd, J=8.6, 5.5 Hz, 2H), 6.89 (t, J=8.7 Hz, 2H), 6.83-6.77 (m, 2H), 4.72 (s, 2H), 4.24 (t, J=6.1 Hz, 2H), 3.70 (s, 3H), 3.55 (dd, J=11.7, 6.2 Hz, 2H), 3.04 (t, J=6.9 Hz, 1H), 2.01-1.86 (m, 2H). LCMS: MH+ 470 and TR=2.811 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-1bdb2935e75a4e09b5909cb6a1158800
Source dataset
uspto-grants-2016_09
Patent number
US09440972B2

Reaction notes

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