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

HRID 1108252Notes

Reaction equation

HRID 1108252 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-a6e55f0edd6f4279990df070a8d160e6
Source dataset
uspto-grants-2000_05
Patent number
US06066638

Reaction notes

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