N,N-Diethyl-1,4-butanediamine → 1-Cyclopentyl-7-(4-diethylamino-butylamino)-3-(2,6-difluoro-3,5-dimethoxy-phenyl)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one

HRID 459967

Reaction equation

HRID 459967 reaction equation
[CH:1]1([N:6]2[C:11]3=[N:12][C:13](S(C)=O)=[N:14][CH:15]=[C:10]3[CH2:9][N:8]([C:19]3[C:24]([F:25])=[C:23]([O:26][CH3:27])[CH:22]=[C:21]([O:28][CH3:29])[C:20]=3[F:30])[C:7]2=[O:31])[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:32]([N:34]([CH2:40][CH3:41])[CH2:35][CH2:36][CH2:37][CH2:38][NH2:39])[CH3:33]>O1CCOCC1>[CH:1]1([N:6]2[C:11]3=[N:12][C:13]([NH:39][CH2:38][CH2:37][CH2:36][CH2:35][N:34]([CH2:40][CH3:41])[CH2:32][CH3:33])=[N:14][CH:15]=[C:10]3[CH2:9][N:8]([C:19]3[C:24]([F:25])=[C:23]([O:26][CH3:27])[CH:22]=[C:21]([O:28][CH3:29])[C:20]=3[F:30])[C:7]2=[O:31])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 117976N,N-Diethyl-1,4-butanediamineHCID 184448441-Cyclopentyl-3-(2,6-difluoro-3,5-dimethoxyphenyl)-7-(methylsulfinyl)-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one

Product 1

HCID 103697821-Cyclopentyl-7-(4-diethylamino-butylamino)-3-(2,6-difluoro-3,5-dimethoxy-phenyl)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-oneYield 86%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

In a 1-L round bottom flask, 8.00 g (17.78 mmol) of 1-cyclopentyl-3-(2,6-difluoro-3,5-dimethoxy-phenyl)-7-methylsulfinyl-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one in 260 mL of dioxane was treated with 5.10 g (35.36 mmol) of 4-diethylamino-butylamine and heated at reflux for 10 hours under nitrogen atmosphere. The dioxane was evaporated in vacuo. The crude product was purified using medium-pressure chromatography eluting with a gradient of 9:0.5:0.25 to 9:1:0.5 ethyl acetate/methanol/triethylamine to give 8.14 g (86%) of the title compound as a pure partially crystalline solid. A 50 mg portion of the solid was recrystallized with 25% ethanol in hexanes to give 35 mg of title compound as pure crystalline solid: mp 132° C.–133° C. MS (APCI) (m+1)/z 533.3.

Workup

  1. temperatureheated
  2. temperatureat reflux for 10 hours under nitrogen atmosphere
  3. customThe dioxane was evaporated in vacuo
  4. customThe crude product was purified
  5. washeluting with a gradient of 9:0.5:0.25 to 9:1:0.5 ethyl acetate/methanol/triethylamine

Sources & evidence

ORD record
ord-4dc2d2c12f8c4774992c7decd3d83954
Source dataset
uspto-grants-2007_03
Patent number
US07196090B2

Linked notes

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