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

HRID 60500Notes

Reaction equation

HRID 60500 reaction equation
C([O:3][CH2:4][CH2:5][CH2:6][N:7]1[C:12](=[O:13])[C:11]2[C:14]([CH2:29][C:30]3[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][CH:31]=3)=[C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([O:24][C:25]([F:28])([F:27])[F:26])[CH:19]=3)[CH:16]=[N:17][C:10]=2[N:9]([CH3:37])[C:8]1=[O:38])=O.O[Li].O>C1COCC1.O.CC(=O)OCC>[Cl:36][C:33]1[CH:34]=[CH:35][C:30]([CH2:29][C:14]2[C:11]3[C:12](=[O:13])[N:7]([CH2:6][CH2:5][CH2:4][OH:3])[C:8](=[O:38])[N:9]([CH3:37])[C:10]=3[N:17]=[CH:16][C:15]=2[C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([O:24][C:25]([F:28])([F:27])[F:26])[CH:19]=2)=[CH:31][CH:32]=1

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 1188754473-(5-(4-chlorobenzyl)-1-methyl-2,4-dioxo-6-(3-(trifluoromethoxy)phenyl)-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate

Product 1

HCID 1188758945-(4-chlorobenzyl)-3-(3-hydroxypropyl)-1-methyl-6-(3-(trifluoromethoxy)phenyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dioneYield 42.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-(5-(4-chlorobenzyl)-1-methyl-2,4-dioxo-6-(3-(trifluoromethoxy)phenyl)-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate (50 mg, 0.091 mmol) in THF (2 ml) and water (2 mL) was added LiOH.H2O (7.6 mg, 0.183 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-(3-(trifluoromethoxy)phenyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (20 mg, 40.5% yield) as a white solid. 1H NMR (CD3OD) δ: 8.52 (s, 1H), 7.49 (t, J=8.0 Hz, 1H), 7.32 (d, J=8.0 Hz, 1H), 7.19 (d, J=8.0 Hz, 1H), 7.15-7.07 (m, 3H), 6.79 (d, J=8.4 Hz, 2H), 4.67 (s, 2H), 4.10 (t, J=6.8 Hz, 2H), 3.74 (s, 3H), 3.57 (t, J=6.4 Hz, 2H), 1.86-1.81 (m, 2H). LCMS: MH+ 520 and TR=3.195 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-2c624f68a21f4103b5d8f25e90a91571
Source dataset
uspto-grants-2016_09
Patent number
US09440972B2

Reaction notes

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