N,N-Dimethylglycine → 6-(2-isopropylphenoxy)-1-methyl-3-(3-(tetra hydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

HRID 60501

Reaction equation

HRID 60501 reaction equation
[Si]([O:8][CH2:9][CH2:10][CH2:11][N:12]1[C:17](=[O:18])[C:16]2[C:19](C(C3C=CC(Cl)=CC=3)O)=[C:20](C3C=CC=CC=3C(C)C)[CH:21]=[N:22][C:15]=2[N:14]([CH3:41])[C:13]1=[O:42])(C(C)(C)C)(C)C.[C:43]([O-])([O-])=O.[Cs+].[Cs+].CN(C)CC(O)=O.[CH:56]([C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][C:60]=1[OH:65])([CH3:58])[CH3:57].O1[CH2:71][CH2:70][O:69][CH2:68][CH2:67]1>[Cu]I>[CH:56]([C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][C:60]=1[O:65][C:20]1[CH:21]=[N:22][C:15]2[N:14]([CH3:41])[C:13](=[O:42])[N:12]([CH2:11][CH2:10][CH2:9][O:8][CH:70]3[CH2:71][CH2:43][CH2:67][CH2:68][O:69]3)[C:17](=[O:18])[C:16]=2[CH:19]=1)([CH3:58])[CH3:57]

Participants

7

Reactant 5

HCID 673N,N-DimethylglycineHCID 69432-IsopropylphenolHCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 1317370933-(3-((tert-butyldimethylsilyl)oxy)propyl)-5-((4-chlorophenyl) (hydroxy)methyl)-6-(2-isopropylphenyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione2×

Product 1

HCID 1188754996-(2-isopropylphenoxy)-1-methyl-3-(3-(tetra hydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dioneYield 55%

Reagents, catalysts & solvents 1

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst

Procedure

To a mixture of 6-bromo-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (See Compound 20, step 4, 400 mg, 1 mmol), CuI (24 mg, 0.13 mmol), Cs2CO3 (650 mg, 2 mmol) and 2-(dimethylamino)acetic acid (51 mg, 0.5 mmol) in dioxane (6 mL) was added 2-isopropylphenol (204 mg, 1.5 mmol). The reaction was heated at 140° C. (MW) for 1.5 h then cooled to RT and filtered. The filtrate was diluted with EA (5 mL) and water (5 mL). The organic layer was dried over Na2SO4 and concentrated to a residue which was purified by chromatography eluted with PE/EA (1:1) to give 6-(2-isopropylphenoxy)-1-methyl-3-(3-(tetra hydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (250 mg, 55% yield) as a solid. LCMS: [MH+-THP] 370 and TR=0.918 min.

Workup

  1. temperatureThe reaction was heated at 140° C. (MW) for 1.5 h
  2. filtrationfiltered
  3. additionThe filtrate was diluted with EA (5 mL) and water (5 mL)
  4. dry with materialThe organic layer was dried over Na2SO4
  5. concentrationconcentrated to a residue which
  6. customwas purified by chromatography
  7. washeluted with PE/EA (1:1)

Sources & evidence

ORD record
ord-2e0f8dbbaacd48aba9a0d9ac3d395af9
Source dataset
uspto-grants-2016_09
Patent number
US09440972B2

Linked notes

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