5-((4-chlorophenyl)(hydroxy)methyl)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)-6-(3-(trifluoromethoxy)phenyl)pyrido[2,3-d]pyrimidine-2,4 (1H,3H)-dione → 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

HRID 60499Notes

Reaction equation

HRID 60499 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8](O)[C:9]2[C:18]3[C:17](=[O:19])[N:16]([CH2:20][CH2:21][CH2:22][O:23][CH:24]4CCCC[O:25]4)[C:15](=[O:30])[N:14]([CH3:31])[C:13]=3[N:12]=[CH:11][C:10]=2[C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([O:38][C:39]([F:42])([F:41])[F:40])[CH:33]=2)=[CH:4][CH:3]=1>C(O)=O.[Zn]>[CH:24]([O:23][CH2:22][CH2:21][CH2:20][N:16]1[C:17](=[O:19])[C:18]2[C:9]([CH2:8][C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=3)=[C:10]([C:32]3[CH:37]=[CH:36][CH:35]=[C:34]([O:38][C:39]([F:41])([F:42])[F:40])[CH:33]=3)[CH:11]=[N:12][C:13]=2[N:14]([CH3:31])[C:15]1=[O:30])=[O:25]

Participants

4

Reactant 1

HCID 1188755535-((4-chlorophenyl)(hydroxy)methyl)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)-6-(3-(trifluoromethoxy)phenyl)pyrido[2,3-d]pyrimidine-2,4 (1H,3H)-dione

Product 1

HCID 1188754473-(5-(4-chlorobenzyl)-1-methyl-2,4-dioxo-6-(3-(trifluoromethoxy)phenyl)-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formateYield 56.5%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 284Formic AcidSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 5-((4-chlorophenyl)(hydroxy)methyl)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)-6-(3-(trifluoromethoxy)phenyl)pyrido[2,3-d]pyrimidine-2,4 (1H,3H)-dione (100 mg, 0.162 mmol) in formic acid (3 mL) was added Zn dust (40.9 mg, 0.641 mmol). The reaction was heated at 50° C. for 2 h, cooled to RT and filtered. The filtrate was concentrated to a residue which was purified by Prep TLC eluted with PE/EA (1:1) to give 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, 56.5% yield) as a white solid. LCMS: MH+ 548 and TR=1.399 min.

Workup

  1. temperaturecooled to RT
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated to a residue which
  4. customwas purified by Prep TLC
  5. washeluted with PE/EA (1:1)

Sources & evidence

ORD record
ord-a8b1b784f91248c5ab4fc153c0576157
Source dataset
uspto-grants-2016_09
Patent number
US09440972B2

Reaction notes

Loading…