5-(4-chlorobenzyl)-6-(3-fluorophenyl)-3-(3-hydroxy propyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione → 5-benzyl-6-(3-fluorophenyl)-3-(3-hydroxypropyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

HRID 60483Notes

Reaction equation

HRID 60483 reaction equation
Cl[C:2]1[CH:32]=[CH:31][C:5]([CH2:6][C:7]2[C:16]3[C:15](=[O:17])[N:14]([CH2:18][CH2:19][CH2:20][OH:21])[C:13](=[O:22])[N:12]([CH3:23])[C:11]=3[N:10]=[CH:9][C:8]=2[C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=2)=[CH:4][CH:3]=1>CO.CC(=O)OCC.O.[Pd]>[CH2:6]([C:7]1[C:16]2[C:15](=[O:17])[N:14]([CH2:18][CH2:19][CH2:20][OH:21])[C:13](=[O:22])[N:12]([CH3:23])[C:11]=2[N:10]=[CH:9][C:8]=1[C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=1)[C:5]1[CH:31]=[CH:32][CH:2]=[CH:3][CH:4]=1

Participants

6

Reactant 1

HCID 1188755565-(4-chlorobenzyl)-6-(3-fluorophenyl)-3-(3-hydroxy propyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

Product 1

HCID 1188755195-benzyl-6-(3-fluorophenyl)-3-(3-hydroxypropyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dioneYield 43.5%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-(4-chlorobenzyl)-6-(3-fluorophenyl)-3-(3-hydroxypropyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (25 mg, 0.06 mmol) in MeOH (1 mL) was added 10% Pd/C (10 mg). The reaction was hydrogenated (15 psi) at 70° C. for 1 h, cooled to RT then diluted with EA (30 mL) and water (30 mL). The organic layer was dried over Na2SO4 and concentrated to a residue which was purified by Prep HPLC to give 5-benzyl-6-(3-fluorophenyl)-3-(3-hydroxypropyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (10 mg, 43.5% yield) as a solid. 1H NMR (CDCl3) δ: 8.52 (s, 1H), 7.35 (d, J=8.0, 6.0 Hz, 1H), 7.23-7.06 (m, 4H), 6.98 (t, J=8.0 Hz, 1H), 6.93-6.87 (m, 1H), 6.84 (d, J=6.9 Hz, 2H), 4.68 (s, 2H), 4.17 (dd, J=20.0, 13.9 Hz, 2H), 3.77 (s, 3H), 3.42 (t, J=5.2 Hz, 2H), 2.89 (s, 1H), 1.91-1.80 (m, 2H). LCMS: MH+ 420 and TR=2.83 min.

Workup

  1. customat 70° C.
  2. customfor 1 h
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated to a residue which
  5. customwas purified by Prep HPLC

Sources & evidence

ORD record
ord-ff6064f6c1ba47a5b5cdd5208cef8146
Source dataset
uspto-grants-2016_09
Patent number
US09440972B2

Reaction notes

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