Hydrochloric Acid → 1-Cyclopentyl-7-(4-diethylamino-butylamino)-3-(2,6-difluoro-3-hydroxy-5-methoxy phenyl)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one

HRID 459966Notes

Reaction equation

HRID 459966 reaction equation
[CH:1]1([N:6]2[C:11]3=[N:12][C:13]([NH:16][CH2:17][CH2:18][CH2:19][CH2:20][N:21]([CH2:24][CH3:25])[CH2:22][CH3:23])=[N:14][CH:15]=[C:10]3[CH2:9][N:8]([C:26]3[C:31]([F:32])=[C:30]([O:33]C)[CH:29]=[C:28]([O:35][CH3:36])[C:27]=3[F:37])[C:7]2=[O:38])[CH2:5][CH2:4][CH2:3][CH2:2]1.ClCCl.O.Cl>CN(C)C=O>[CH:1]1([N:6]2[C:11]3=[N:12][C:13]([NH:16][CH2:17][CH2:18][CH2:19][CH2:20][N:21]([CH2:22][CH3:23])[CH2:24][CH3:25])=[N:14][CH:15]=[C:10]3[CH2:9][N:8]([C:26]3[C:27]([F:37])=[C:28]([O:35][CH3:36])[CH:29]=[C:30]([OH:33])[C:31]=3[F:32])[C:7]2=[O:38])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 313Hydrochloric Acid2×HCID 962WaterHCID 6344DichloromethaneHCID 103697821-Cyclopentyl-7-(4-diethylamino-butylamino)-3-(2,6-difluoro-3,5-dimethoxy-phenyl)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one

Product 1

HCID 98066541-Cyclopentyl-7-(4-diethylamino-butylamino)-3-(2,6-difluoro-3-hydroxy-5-methoxy phenyl)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of sodium ethylthiolate [generated from sodium hydride (200 mg, 8.32 mmol) and ethanethiol (616 μL, 8.32 mmol) in dimethylformamide (20 mL)], 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 in dimethylformamide (8 mL) was added. The resulting solution was then stirred at 75° C. for 90 minutes. The solvent was removed under reduced pressure to afford a light brown oil. Dichloromethane (100 mL) and water (20 mL) were added. The bilayer thus afforded was then stirred vigorously while 4 N hydrochloric acid was added. Enough hydrochloric acid was added until the aqueous layer reached pH=5. The layers were separated; the aqueous layer was extracted with dichloromethane (2×80 mL). The organic layers were combined and set aside. Saturated aqueous sodium chloride (20 mL) was to the aqueous layers and was extracted with ethyl acetate (2×80 mL). The organic layers were combined, dried (magnesium sulfate), filtered, and concentrated under reduced pressure. To the yellow oil (794 mg) thus afforded, hexanes were added to remove non-polar impurities. The supernatant was removed, and the remaining residue was placed in vacuo. The oil was purified via reverse phase HPLC to give the title compound (289 mg, 54%) as a clear amber gum: MS (APCI) 519.2, 520.2.

Workup

  1. customThe solvent was removed under reduced pressure
  2. customto afford a light brown oil
  3. customThe bilayer thus afforded
  4. additionwas added
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with dichloromethane (2×80 mL)
  7. extractionwas extracted with ethyl acetate (2×80 mL)
  8. dry with materialdried (magnesium sulfate)
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-78ab60b01ac74bdb82fd058ca5977a1a
Source dataset
uspto-grants-2007_03
Patent number
US07196090B2

Reaction notes

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