5-((4-chlorophenyl)(hydroxy)methyl)-6-((5-fluoropyridin-3-yl)oxy)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione → 3-(5-(4-chlorobenzyl)-6-((5-fluoropyridin-3-yl)oxy)-1-methyl-2,4-dioxo-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate

HRID 60424Notes

Reaction equation

HRID 60424 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[O:32][C:33]2[CH:34]=[N:35][CH:36]=[C:37]([F:39])[CH:38]=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]([O:32][C:33]3[CH:34]=[N:35][CH:36]=[C:37]([F:39])[CH:38]=3)[CH:11]=[N:12][C:13]=2[N:14]([CH3:31])[C:15]1=[O:30])=[O:25]

Participants

4

Reactant 1

HCID 1188754815-((4-chlorophenyl)(hydroxy)methyl)-6-((5-fluoropyridin-3-yl)oxy)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

Product 1

HCID 1188759013-(5-(4-chlorobenzyl)-6-((5-fluoropyridin-3-yl)oxy)-1-methyl-2,4-dioxo-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formateYield 69.7%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 284Formic AcidSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 5-((4-chlorophenyl)(hydroxy)methyl)-6-((5-fluoropyridin-3-yl)oxy)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (45 mg, 0.092 mmol) in HCOOH (5 mL) was added Zn dust (30.2 mg, 0.462 mmol). The reaction was heated at 70° C. for 1.5 h, cooled to RT and filtered. The filtrate was concentrated and dried to a residue which was purified by chromatography eluted with PE/EA (10:1 to 1:1) to give 3-(5-(4-chlorobenzyl)-6-((5-fluoropyridin-3-yl)oxy)-1-methyl-2,4-dioxo-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate (32 mg, 69.4% yield) as an oil. LCMS: MH+ 499 and TR=1.513 min.

Workup

  1. temperaturecooled to RT
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated
  4. customdried to a residue which
  5. customwas purified by chromatography
  6. washeluted with PE/EA (10:1 to 1:1)

Sources & evidence

ORD record
ord-e25c6d2bc0b641c991eec940dca40ca5
Source dataset
uspto-grants-2016_09
Patent number
US09440972B2

Reaction notes

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