Pyridine → HCID 60123476, compound

HRID 2416430Notes

Reaction equation

HRID 2416430 reaction equation
[CH3:1][N:2]1[C:7]2[NH:8][C:9]([CH3:13])=[CH:10][C:11](=O)[C:6]=2[C:5](=[O:14])[N:4]([CH2:15][CH2:16][CH2:17][CH2:18][C@H:19]([N:21]([CH3:23])[CH3:22])[CH3:20])[C:3]1=[O:24].[N:25]1[CH:30]=CC=C[CH:26]=1.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O>ClCCl>[CH3:1][N:2]1[C:7]2[N:8]=[C:9]([CH3:13])[CH:10]=[C:11]([N:25]([CH3:30])[CH3:26])[C:6]=2[C:5](=[O:14])[N:4]([CH2:15][CH2:16][CH2:17][CH2:18][C@H:19]([N:21]([CH3:23])[CH3:22])[CH3:20])[C:3]1=[O:24]

Participants

5

Reactant 3

HCID 1049PyridineHCID 67749Trifluoromethanesulfonic anhydrideHCID 60123477476623-49-1

Product 1

HCID 60123476HCID 60123476, compoundYield 88%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
55 °C

Procedure

To a mixture of (R)-1,7-dimethyl-3-(5-(N,N-dimethylamino)hexyl)pyrido[2,3-d]pyrimidine-2,4,5(1H,3H,8H)-trione (315 mg, 0.947 mmol), pyridine (1 ml, 12.4 mmol) and dichloromethane (20 ml), cooled in an ice bath, was added trifluoromethanesulfonic anhydride (0.315 ml, 1.87 mmol) dropwise. After stirring for 2 hours, the cooling bath was removed. A 30% (v:v) solution of dimethylamine in tetrahydrofuran (7 ml) was added and the solution was transferred to a pressure tube (1″×8″). The tube was sealed and heated to 55° C. for 2 hours. After cooling to room temperature the solution was concentrated under reduced pressure. The residue was dissolved in ethyl acetate and the solution filtered through a pad of celite. The filtrate was rinsed with saturated sodium bicarbonate solution, dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel eluting with ethyl acetate-methanol-triethylamine (85:10:5) to afford (R)-1,7-Dimethyl-5-(N,N-dimethylamino)-3-(5-(N,N-dimethylamino)hexyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)dione (300 mg, 88% yield for 2 steps) as an oil. 1H NMR (300 MHz, CDCl3) δ 0.99 (d, 3H), 1.20-1.50 (m, 3H), 1.52-1.74 (m, 3H), 2.28 (s, 6H), 2.42 (s, 3H), 2.99 (s, 6H), 3.64 (s, 3H), 4.03 (t, 2H), 6.39 (s, 1H).

Workup

  1. temperaturecooled in an ice bath
  2. customthe cooling bath was removed
  3. additionA 30% (v:v) solution of dimethylamine in tetrahydrofuran (7 ml) was added
  4. customthe solution was transferred to a pressure tube
  5. customThe tube was sealed
  6. temperatureAfter cooling to room temperature the solution
  7. concentrationwas concentrated under reduced pressure
  8. dissolutionThe residue was dissolved in ethyl acetate
  9. filtrationthe solution filtered through a pad of celite
  10. washThe filtrate was rinsed with saturated sodium bicarbonate solution
  11. dry with materialdried over sodium sulfate
  12. concentrationconcentrated under reduced pressure
  13. customThe residue was purified by column chromatography on silica gel eluting with ethyl acetate-methanol-triethylamine (85:10:5)

Sources & evidence

ORD record
ord-7ff2cde7d8c24bd39bcfc35fae5b404a
Source dataset
uspto-grants-2004_11
Patent number
US06825180B2

Reaction notes

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