Lithium hydroxide, monohydrate → 5-(4-chlorobenzyl)-6-((5-chloropyridin-3-yl)oxy)-3-(3-hydroxypropyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

HRID 60429Notes

Reaction equation

HRID 60429 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]([Cl:33])=[CH:29][CH:28]=3)=[C:15]([O:18][C:19]3[CH:20]=[N:21][CH:22]=[C:23]([Cl:25])[CH:24]=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:33][C:30]1[CH:29]=[CH:28][C:27]([CH2:26][C:14]2[C:11]3[C:12](=[O:13])[N:7]([CH2:6][CH2:5][CH2:4][OH:3])[C:8](=[O:35])[N:9]([CH3:34])[C:10]=3[N:17]=[CH:16][C:15]=2[O:18][C:19]2[CH:20]=[N:21][CH:22]=[C:23]([Cl:25])[CH:24]=2)=[CH:32][CH:31]=1

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 118875885HCID 118875885, compound

Product 1

HCID 1188755155-(4-chlorobenzyl)-6-((5-chloropyridin-3-yl)oxy)-3-(3-hydroxypropyl)-1-methylpyrido[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-(4-chlorobenzyl)-6-((5-chloropyridin-3-yl)oxy)-1-methyl-2,4-dioxo-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate (40 mg, 0.078 mmol) in THF (6 mL) and water (6 mL) was added LiOH.H2O (6.51 mg, 0.156 mmol) at 20° C. 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 5-(4-chlorobenzyl)-6-((5-chloropyridin-3-yl)oxy)-3-(3-hydroxypropyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (8 mg, 21.2% yield) as a white solid. 1H NMR (CDCl3) δ: 8.52 (s, 1H), 8.39 (d, J=3.0 Hz, 1H), 8.10 (s, 1H), 7.71 (d, J=3.0 Hz, 1H), 7.17 (d, J=8.5 Hz, 2H), 7.11 (d, J=8.4 Hz, 2H), 4.24 (t, J=6.1 Hz, 2H), 4.19 (s, 2H), 3.72 (s, 3H), 3.57 (d, J=5.0 Hz, 2H), 2.99 (s, 1H), 2.00-1.85 (m, 2H). LCMS MH+ 487 and TR=2.436 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-a705385c40a345a78faf1ff8cfeb5342
Source dataset
uspto-grants-2016_09
Patent number
US09440972B2

Reaction notes

Loading…