N,N-Dimethylglycine → HCID 118875532, compound

HRID 60472Notes

Reaction equation

HRID 60472 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.[Cl:47][C:48]1[CH:53]=[CH:52][C:51]([OH:54])=[CH:50][CH:49]=1>O1CCOCC1.[Cu]I>[Cl:47][C:48]1[CH:53]=[CH:52][C:51]([O:54][C:2]2[CH:24]=[N:23][C:5]3[N:6]([CH3:22])[C:7](=[O:21])[N:8]([CH2:11][CH2:12][CH2:13][O:14][CH:15]4[CH2:20][CH2:19][CH2:18][CH2:17][O:16]4)[C:9](=[O:10])[C:4]=3[CH:3]=2)=[CH:50][CH:49]=1

Participants

7

Reactant 4

HCID 673N,N-DimethylglycineHCID 46844-ChlorophenolHCID 10796Cesium carbonateHCID 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 118875532HCID 118875532, compoundYield 56.2%

Reagents, catalysts & solvents 2

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

Procedure

To a mixture of 6-(4-chlorophenoxy)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (See Compound 20, step 4400 mg, 1 mmol), CuI (24.7 mg, 0.13 mmol), Cs2CO3 (650 mg, 2 mmol), 2-(dimethylamino)acetic acid (51.5 mg, 0.5 mmol) in dioxane (6 mL) was added 4-chlorophenol (192 mg, 1.5 mmol). The reaction was heated at 140° C. (MW) for 1.5 h, 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-(4-chlorophenoxy)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (250 mg, 56.2% yield) as an oil. LCMS: MH+ 446 and TR=3.000 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-20fc8483757b489d85f1927eb2a71dc9
Source dataset
uspto-grants-2016_09
Patent number
US09440972B2

Reaction notes

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