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

HRID 60437Notes

Reaction equation

HRID 60437 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][C:22]([CH3:25])=[CH:23][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][C:22]([CH3:25])=[CH:23][CH:24]=2)=[CH:32][CH:31]=1

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 1188759053-(5-(4-chlorobenzyl)-1-methyl-6-((6-methylpyridin-3-yl)oxy)-2,4-dioxo-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate

Product 1

HCID 1188755175-(4-chlorobenzyl)-3-(3-hydroxypropyl)-1-methyl-6-((6-methylpyridin-3-yl)oxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dioneYield 21.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-(5-(4-chlorobenzyl)-1-methyl-6-((6-methylpyridin-3-yl)oxy)-2,4-dioxo-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate (10 mg, 0.020 mmol) in THF (5 mL) and water (5 mL) was added LiOH.H2O (1.70 mg, 0.040 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 5-(4-chlorobenzyl)-3-(3-hydroxypropyl)-1-methyl-6-((6-methylpyridin-3-yl)oxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (2 mg, 21.2% yield) as a white solid. 1H NMR (CDCl3) δ: 8.29 (s, 1H), 8.20 (d, J=2.4 Hz, 1H), 7.16-7.18 (m, 4H), 7.10 (d, J=8.6 Hz, 1H), 7.03 (s, 1H), 4.76 (s, 2H), 4.24 (t, J=6.2 Hz, 2H), 3.70 (s, 3H), 3.53-3.57 (m, 2H), 3.04 (t, J=7.0 Hz, 1H), 2.54 (s, 3H), 1.92-1.96 (m, 2H). LCMS: MH+ 467 and TR=1.903 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-d15b641a25a743d1b7830a9324d1d521
Source dataset
uspto-grants-2016_09
Patent number
US09440972B2

Reaction notes

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