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

HRID 60433Notes

Reaction equation

HRID 60433 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]([O:18][C:19]3[CH:20]=[N:21][CH:22]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:24]=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:32]=[CH:31][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[O:18][C:19]2[CH:20]=[N:21][CH:22]=[C:23]([C:25]([F:27])([F:26])[F:28])[CH:24]=2)=[CH:35][CH:34]=1

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 1188759123-(5-(4-chlorobenzyl)-1-methyl-2,4-dioxo-6-((5-(trifluoromethyl)pyridin-3-yl)oxy)-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate

Product 1

HCID 1188755485-(4-chlorobenzyl)-3-(3-hydroxypropyl)-1-methyl-6-((5-(trifluoromethyl)pyridin-3-yl)oxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dioneYield 18.6%

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-((5-(trifluoromethyl)pyridin-3-yl)oxy)-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate (45.3 mg, 0.083 mmol) in THF (5 mL) and water (5 mL) was added LiOH.H2O (6.93 mg, 0.165 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-((5-(trifluoromethyl)pyridin-3-yl)oxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (8 mg, 18.6% yield) as a white solid. 1H NMR (CDCl3) δ: 8.82 (s, 1H), 8.35 (s, 1H), 8.26 (d, J=3.0 Hz, 1H), 7.53 (d, J=3.0 Hz, 1H), 7.12 (d, J=8.4 Hz, 2H), 7.01 (d, J=8.3 Hz, 2H), 4.26-4.20 (m, 4H), 3.71 (s, 3H), 3.58-3.54 (m, 2H), 2.97 (brd s, 1H), 1.96-1.90 (m, 2H). LCMS: MH+ 521 and TR=2.765 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-579955d2ec8943b5ac1506b68a464f9f
Source dataset
uspto-grants-2016_09
Patent number
US09440972B2

Reaction notes

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