Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → 1-Cyclopentyl-7-[4-(piperidin-1-yl)phenylamino]-3,4-dihydro-pyrimido[4,5-d]pyrimidin-2(1H)-one

HRID 1783512Notes

Reaction equation

HRID 1783512 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[CH:14]1([N:19]2[C:24]3=[N:25][C:26](S(C)=O)=[N:27][CH:28]=[C:23]3[CH2:22][NH:21][C:20]2=[O:32])[CH2:18][CH2:17][CH2:16][CH2:15]1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.O1CCOCC1>C(Cl)(Cl)Cl.C(OCC)(=O)C>[CH:14]1([N:19]2[C:24]3=[N:25][C:26]([NH:1][C:2]4[CH:3]=[CH:4][C:5]([N:8]5[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]5)=[CH:6][CH:7]=4)=[N:27][CH:28]=[C:23]3[CH2:22][NH:21][C:20]2=[O:32])[CH2:15][CH2:16][CH2:17][CH2:18]1

Participants

7

Reactant 4

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 312751,4-DioxaneHCID 4135014-(Piperidin-1-yl)anilineHCID 688593421-cyclopentyl-7-methanesulfinyl-3,4-dihydro-pyrimido[4,5-d]pyrimidin-2(1H)-one

Product 1

HCID 688602801-Cyclopentyl-7-[4-(piperidin-1-yl)phenylamino]-3,4-dihydro-pyrimido[4,5-d]pyrimidin-2(1H)-oneYield 24%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolvent4×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 377 mg (2.14 mmol) of 1-(4-aminophenyl)piperidine, 300 mg (1.07 mmol) of 1-cyclopentyl-7-methanesulfinyl-3,4-dihydro-pyrimido[4,5-d]pyrimidin-2(1H)-one, 745 mg (3.21 mmol) of camphorsulfonic acid, and 2 mL of p-dioxane is heated at 130° C. for 1 hour in a sealed tube. The mixture is cooled and diluted with chloroform. The solution is washed twice with saturated aqueous sodium bicarbonate and once each with aqueous sodium chloride then brine. The organic phase is dried over magnesium sulfate and concentrated to leave a dark green residue that is dissolved in chloroform and chromatographed on silica gel eluting with 9:1:0.5 ethyl acetate/ethanol/triethylamine. The product fractions are pooled and concentrated to leave a residue that is dissolved in chloroform. The solution is diluted with ethyl acetate while most of the chloroform is being boiled away. Upon cooling, crystals form and are then collected to leave 101 mg (24%) of the title compound:

Workup

  1. temperatureThe mixture is cooled
  2. washThe solution is washed twice with saturated aqueous sodium bicarbonate
  3. dry with materialThe organic phase is dried over magnesium sulfate
  4. concentrationconcentrated
  5. customto leave a dark green residue that
  6. customchromatographed on silica gel eluting with 9:1:0.5 ethyl acetate/ethanol/triethylamine
  7. concentrationconcentrated
  8. customto leave a residue that
  9. temperatureUpon cooling
  10. customcrystals form and are then collected

Sources & evidence

ORD record
ord-509bd9f1df3a469ea279ff706e84076c
Source dataset
uspto-grants-2009_03
Patent number
US07501425B1

Reaction notes

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