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

HRID 60477Notes

Reaction equation

HRID 60477 reaction equation
C([O:3][CH2:4][CH2:5][CH2:6][N:7]1[C:12](=[O:13])[C:11]2[C:14]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)=[C:15]([O:18][CH:19]([CH3:21])[CH3:20])[CH:16]=[N:17][C:10]=2[N:9]([CH3:30])[C:8]1=[O:31])=O.O[Li].O>C1COCC1.O.CC(=O)OCC>[F:29][C:26]1[CH:25]=[CH:24][C:23]([CH2:22][C:14]2[C:11]3[C:12](=[O:13])[N:7]([CH2:6][CH2:5][CH2:4][OH:3])[C:8](=[O:31])[N:9]([CH3:30])[C:10]=3[N:17]=[CH:16][C:15]=2[O:18][CH:19]([CH3:20])[CH3:21])=[CH:28][CH:27]=1

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 1188758913-(5-(4-fluorobenzyl)-6-isopropoxy-1-methyl-2,4-dioxo-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate

Product 1

HCID 1188755315-(4-fluorobenzyl)-3-(3-hydroxypropyl)-6-isopropoxy-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dioneYield 36%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-(5-(4-fluorobenzyl)-6-isopropoxy-1-methyl-2,4-dioxo-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate (89 mg, 0.21 mmol) in THF (3 mL) and water (3 mL) was added LiOH.H2O (17.4 mg, 0.42 mmol). The reaction was stirred at RT for 15 min then diluted with EA (20 mL) and water (20 mL). The organic layer was dried over Na2SO4 and concentrated to a residue which was purified by Prep HPLC to give 5-(4-fluorobenzyl)-3-(3-hydroxypropyl)-6-isopropoxy-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (30 mg, 36% yield) as a white solid. 1H NMR (CDCl3) δ: 8.33 (s, 1H), 7.22 (dd, J=8.6, 5.5 Hz, 2H), 6.95-6.84 (m, 2H), 4.73 (s, 2H), 4.64 (dt, J=12.1, 6.0 Hz, 1H), 4.27-4.15 (m, 2H), 3.69 (s, 3H), 3.52 (dd, J=11.6, 6.1 Hz, 2H), 3.19 (t, J=6.9 Hz, 1H), 1.96-1.84 (m, 2H), 1.35 (d, J=6.0 Hz, 6H). LCMS: MH+ 402 and TR=2.728 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-383f08587dad4385be852c48c55b09c6
Source dataset
uspto-grants-2016_09
Patent number
US09440972B2

Reaction notes

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