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

HRID 60491Notes

Reaction equation

HRID 60491 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]([Cl: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>[Cl: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

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 1188758883-(5-(4-chlorobenzyl)-6-isopropoxy-1-methyl-2,4-dioxo-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate

Product 1

HCID 1188755055-(4-chlorobenzyl)-3-(3-hydroxypropyl)-6-isopropoxy-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dioneYield 37%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-(5-(4-chlorobenzyl)-6-isopropoxy-1-methyl-2,4-dioxo-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate (55 mg, 0.13 mmol) in THF (6 mL) and water (6 mL) was added LiOH.H2O (10.9 mg, 0.26 mmol). The reaction was stirred at RT for 15 min then diluted with water (20 mL) and extracted with EA (3×15 mL). The combined organic layers were dried over Na2SO4 and concentrated to a residue which was purified by Prep HPLC to give 5-(4-chlorobenzyl)-3-(3-hydroxypropyl)-6-isopropoxy-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (20 mg, 37% yield) as a white solid. 1H NMR (CDCl3) δ: 8.33 (s, 1H), 7.18 (s, 4H), 4.73 (s, 2H),), 4.68-4.68 (m, 1H), 4.28-4.15 (m, 2H), 3.69 (s, 3H), 3.52 (dd, J=11.8, 6.2 Hz, 2H), 3.16 (t, J=7.0 Hz, 1H), 1.97-1.82 (m, 2H), 1.34 (d, J=6.0 Hz, 6H). LCMS: MH+ 418 and TR=2.915 min.

Workup

  1. extractionextracted with EA (3×15 mL)
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. concentrationconcentrated to a residue which
  4. customwas purified by Prep HPLC

Sources & evidence

ORD record
ord-58dd988999f246d5bb41b9c0dd4a93bc
Source dataset
uspto-grants-2016_09
Patent number
US09440972B2

Reaction notes

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