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

HRID 60443Notes

Reaction equation

HRID 60443 reaction equation
[Br:1][C:2]1[CH:18]=[N:17][C:5]2[N:6]([CH3:16])[C:7](=[O:15])[N:8]([CH2:11][CH2:12][CH2:13][OH:14])[C:9](=[O:10])[C:4]=2[CH:3]=1.[O:19]1[CH:24]=[CH:23][CH2:22][CH2:21][CH2:20]1>C(Cl)Cl.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1>[Br:1][C:2]1[CH:18]=[N:17][C:5]2[N:6]([CH3:16])[C:7](=[O:15])[N:8]([CH2:11][CH2:12][CH2:13][O:14][CH:20]3[CH2:21][CH2:22][CH2:23][CH2:24][O:19]3)[C:9](=[O:10])[C:4]=2[CH:3]=1

Participants

5

Reactant 2

HCID 80803,4-dihydro-2H-pyranHCID 1188759026-bromo-3-(3-hydroxypropyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

Product 1

HCID 1188755356-bromo-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dioneYield 31.8%

Reagents, catalysts & solvents 2

HCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)CatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 6-bromo-3-(3-hydroxypropyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (6.2 g, 19.8 mmol) in DCM (100 mL) at 0° C. was added 3,4-dihydro-2H-pyran (6 mL, 65.7 mmol) and pyridinium p-toluenesulfonate (50 mg, 0.2 mmol). The reaction was stirred at RT for 16 h then diluted with DCM (100 mL). The organic layer was washed with brine (100 mL), dried over Na2SO4 and concentrated to a residue which was purified by chromatography PE/EA (8:1 to 2:1) to give 6-bromo-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (2.5 g, 31.8% yield) as a white solid. 1H NMR (CDCl3) δ: 8.68 (m, 1H), 8.54-8.53 (m, 1H), 4.57 (s, 1H), 4.26-4.17 (m, 2H), 3.87-3.80 (m, 2H), 3.68 (s, 3H), 3.52-3.47 (m, 2H), 2.04-1.97 (m, 2H), 1.76-1.63 (m, 2H), 1.49-1.46 (m, 2H). LCMS: [MH+-THP] 314 and TR=1.626 min.

Workup

  1. washThe organic layer was washed with brine (100 mL)
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated to a residue which
  4. customwas purified by chromatography PE/EA (8:1 to 2:1)

Sources & evidence

ORD record
ord-250d8b8fdfb34b16b57b0a26500a7b87
Source dataset
uspto-grants-2016_09
Patent number
US09440972B2

Reaction notes

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