Potassium Carbonate → 3-(cyclopropylmethyl)-6-iodo-2-(propylthio)pyrido[2,3-d]pyrimidin-4(3H)-one

HRID 1066879Notes

Reaction equation

HRID 1066879 reaction equation
[CH:1]1([CH2:4][N:5]2[C:10](=[O:11])[C:9]3[CH:12]=[C:13]([I:16])[CH:14]=[N:15][C:8]=3[NH:7][C:6]2=[S:17])[CH2:3][CH2:2]1.[CH2:18](I)[CH2:19][CH3:20].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH:1]1([CH2:4][N:5]2[C:10](=[O:11])[C:9]3[CH:12]=[C:13]([I:16])[CH:14]=[N:15][C:8]=3[N:7]=[C:6]2[S:17][CH2:18][CH2:19][CH3:20])[CH2:2][CH2:3]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 336431-IodopropaneHCID 211962843-(Cyclopropylmethyl)-2,3-dihydro-6-iodo-2-thioxopyrido[2,3-d]pyrimidin-4(1h)-one

Product 1

HCID 155103413-(cyclopropylmethyl)-6-iodo-2-(propylthio)pyrido[2,3-d]pyrimidin-4(3H)-oneYield 89.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of the title compound of Step A (0.5 g, 1.39 mmol), n-propyl iodide (0.36 g, 2.09 mmol) and potassium carbonate (1.9 g, 13.9 mmol) in DMF (14 mL) were stirred at ambient temperature overnight. The reaction mixture was then concentrated to dryness in vacuo and the residue partitioned between 200 mL of ethyl acetate and 100 mL of H2O. The organic phase was separated, washed with saturated aqueous NaCl, dried over Na2SO4 and concentrated in vacuo to provide 0.5 g of crude product. Purification of this crude product was achieved via column chromatography (silica gel, 70:30 hexanes:ethyl acetate eluent) to deliver 0.19 g of the title compound of Step B, a compound of the invention, as a solid melting at 159-161° C. 1H NMR (300 MHz, CDCl3): δ 0.50-0.62 (m,4H), 1.10 (t,3H), 1.31-1.43 (m,1H), 1.79-1.94 (m,2H), 3.41 (t,2H), 4.10 (d,2H), 8.82 (s,1H), 9.02 (d,1H). Mass Spectrum: m/e 402 (protonated parent molecular ion measured by mass spectrometry using atmospheric pressure chemical ionization in the positive ion mode (APCI+); the ion shown corresponds to the M+H+ ion calculated from the integral values of the atomic weights of the most abundant isotope of each element present).

Workup

  1. concentrationThe reaction mixture was then concentrated to dryness in vacuo
  2. customthe residue partitioned between 200 mL of ethyl acetate and 100 mL of H2O
  3. customThe organic phase was separated
  4. washwashed with saturated aqueous NaCl
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5397a25ff0684ccdb72bc338e0cdd929
Source dataset
uspto-grants-2001_06
Patent number
US06245770B1

Reaction notes

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