N,N-Dimethylglycine → 5-(4-chlorobenzyl)-6-(3-chlorophenoxy)-3-(3-hydroxypropyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

HRID 60462

Reaction equation

HRID 60462 reaction equation
C([O:3][CH2:4][CH2:5][CH2:6][N:7]1[C:12](=[O:13])[C:11]2[C:14]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)=[C:15](Br)[CH:16]=[N:17][C:10]=2[N:9]([CH3:27])[C:8]1=[O:28])=O.C([O-])([O-])=O.[Cs+].[Cs+].CN(C)CC(O)=O.[Cl:42][C:43]1[CH:44]=[C:45]([OH:49])[CH:46]=[CH:47][CH:48]=1>O1CCOCC1.CC(=O)OCC.O.[Cu]I>[Cl:26][C:23]1[CH:24]=[CH:25][C:20]([CH2:19][C:14]2[C:11]3[C:12](=[O:13])[N:7]([CH2:6][CH2:5][CH2:4][OH:3])[C:8](=[O:28])[N:9]([CH3:27])[C:10]=3[N:17]=[CH:16][C:15]=2[O:49][C:45]2[CH:46]=[CH:47][CH:48]=[C:43]([Cl:42])[CH:44]=2)=[CH:21][CH:22]=1

Participants

9

Reactant 4

HCID 673N,N-DimethylglycineHCID 79333-ChlorophenolHCID 10796Cesium carbonateHCID 1188758893-(6-bromo-5-(4-chlorobenzyl)-1-methyl-2,4-dioxo-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate

Product 1

HCID 1188755525-(4-chlorobenzyl)-6-(3-chlorophenoxy)-3-(3-hydroxypropyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dioneYield 12.3%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a mixture of 3-(6-bromo-5-(4-chlorobenzyl)-1-methyl-2,4-dioxo-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate (80 mg, 0.17 mmol), CuI (4.2 mg, 0.022 mmol), Cs2CO3 (167.6 mg, 0.51 mmol) and 2-(dimethylamino)acetic acid (8.8 mg, 0.085 mmol) in dioxane (2 mL) was added 3-chlorophenol (55.1 mg, 0.43 mmol). The reaction was heated at 140° C. (MW) for 2 h, cooled to RT then diluted with EA (15 mL) and water (10 mL). The organic layer was washed with water (20 mL) and brine (20 mL), dried over Na2SO4 and concentrated to a residue which was purified by Prep HPLC to give 5-(4-chlorobenzyl)-6-(3-chlorophenoxy)-3-(3-hydroxypropyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (10.2 mg, 12% yield) as a white solid. 1H NMR (CDCl3) δ: 8.35 (s, 1H), 7.23 (d, J=8.2 Hz, 1H), 7.17 (s, 4H), 7.09 (d, J=8.0 Hz, 1H), 6.84-6.73 (m, 2H), 4.71 (s, 2H), 4.24 (t, J=6.1 Hz, 2H), 3.72 (s, 3H), 3.55 (s, 2H), 3.02 (s, 1H), 2.00-1.86 (m, 2H). LCMS: MH+ 486 and TR=3.332 min.

Workup

  1. temperatureThe reaction was heated at 140° C. (MW) for 2 h
  2. washThe organic layer was washed with water (20 mL) and brine (20 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated to a residue which
  5. customwas purified by Prep HPLC

Sources & evidence

ORD record
ord-df7734060bd141cfb0f8840a3b4d8a02
Source dataset
uspto-grants-2016_09
Patent number
US09440972B2

Linked notes

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