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

HRID 60465Notes

Reaction equation

HRID 60465 reaction equation
Br[C:2]1[CH:24]=[N:23][C:5]2[N:6]([CH3:22])[C:7](=[O:21])[N:8]([CH2:11][CH2:12][CH2:13][O:14][CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][O:16]3)[C:9](=[O:10])[C:4]=2[C:3]=1C(C1C=CC(Cl)=CC=1)O.C([O-])([O-])=O.[Cs+].[Cs+].CN(C)CC(O)=O.[CH:47]([C:50]1[CH:51]=[C:52]([OH:56])[CH:53]=[CH:54][CH:55]=1)([CH3:49])[CH3:48]>O1CCOCC1.[Cu]I>[CH:47]([C:50]1[CH:51]=[C:52]([CH:53]=[CH:54][CH:55]=1)[O:56][C:2]1[CH:24]=[N:23][C:5]2[N:6]([CH3:22])[C:7](=[O:21])[N:8]([CH2:11][CH2:12][CH2:13][O:14][CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][O:16]3)[C:9](=[O:10])[C:4]=2[CH:3]=1)([CH3:49])[CH3:48]

Participants

7

Reactant 4

HCID 673N,N-DimethylglycineHCID 10796Cesium carbonateHCID 120593-IsopropylphenolHCID 1188755116-bromo-5-((4-chlorophenyl)(hydroxy)methyl)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione2×

Product 1

HCID 1188755256-(3-isopropylphenoxy)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dioneYield 55.1%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution 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 (24.7 mg, 0.13 mmol), Cs2CO3 (650 mg, 2 mmol) and 2-(dimethylamino)acetic acid (51.5 mg, 0.5 mmol) in dioxane (6 mL) was added 3-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 (5:1) to give 6-(3-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+ 454 and TR=2.156 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 (5:1)

Sources & evidence

ORD record
ord-33e80a485b0541df97b3b92a317c1782
Source dataset
uspto-grants-2016_09
Patent number
US09440972B2

Reaction notes

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