Lithium hydroxide, monohydrate → HCID 118875497, compound

HRID 60439Notes

Reaction equation

HRID 60439 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][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:23][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][C:22]([C:25]([F:27])([F:26])[F:28])=[CH:23][CH:24]=2)=[CH:35][CH:34]=1

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 1188758903-(5-(4-chlorobenzyl)-1-methyl-2,4-dioxo-6-(6-(trifluoromethyl)pyridin-3-yloxy)-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate

Product 1

HCID 118875497HCID 118875497, compoundYield 34.7%

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-(6-(trifluoromethyl)pyridin-3-yloxy)-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate (20 mg, 0.036 mmol) in THF (2 mL) and water (2 mL) was added LiOH.H2O (4.6 mg, 0.109 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 filtered and concentrated to a residue which was purified by Prep HPLC to give 5-(4-chlorobenzyl)-3-(3-hydroxypropyl)-1-methyl-6-(6-(trifluoromethyl)pyridin-3-yloxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (6.5 mg, 34.2% yield) as a white solid. 1H NMR (CDCl3) δ: 8.44 (d, J=3.2 Hz, 1H), 8.21 (s, 1H), 7.84 (d, J=3.2 Hz, 1H), 7.57 (s, 1H), 7.28-7.24 (overlap with CDCl3, 2H), 7.12 (t, J=8.8 Hz, 2H), 4.25 (t, J=6.0 Hz, 2H), 4.08 (s, 2H), 3.74 (s, 3H), 3.61-3.54 (m, 2H), 2.93 (brd s, 1H), 1.97-1.90 (m, 2H). LCMS: MH+ 521 and TR=2.625 min.

Workup

  1. dry with materialThe organic layer was dried over Na2SO4
  2. filtrationfiltered
  3. concentrationconcentrated to a residue which
  4. customwas purified by Prep HPLC

Sources & evidence

ORD record
ord-65095e0400fc4180bb2563cfc734127b
Source dataset
uspto-grants-2016_09
Patent number
US09440972B2

Reaction notes

Loading…