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

HRID 60432Notes

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]([C:39]([F:42])([F:41])[F:40])[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]([C:39]([F:41])([F:42])[F:40])[CH:38]=3)[CH:11]=[N:12][C:13]=2[N:14]([CH3:31])[C:15]1=[O:30])=[O:25]

Participants

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-((5-(trifluoromethyl)pyridin-3-yl)oxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (172 mg, 0.277 mmol) in HCOOH (5 mL) was added Zn dust (88.5 mg, 1.385 mmol) at 20° C. 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-((5-(trifluoromethyl)pyridin-3-yl)oxy)-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate (45.3 mg, 29.8% yield) as an oil. LCMS: MH+ 549 and TR=1.471 min.

Workup

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

Sources & evidence

ORD record: ord-caa15a68f7dd4da8b05cc1989f7dad3c
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09440972B2

Reaction notes

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