(+/-)-1-[1-(2-Chloro-pyrimidin-5-yl)-ethyl]-1-(2-fluoro-4-methoxy-phenyl)-3-phenyl-urea → (+/-)-7-chloro-3-(2-fluoro-4-methoxy-phenyl)-4-methyl-1-phenyl-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one

HRID 2216973Notes

Reaction equation

HRID 2216973 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH:8]([N:10]([C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][C:21]=2[F:28])[C:11]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:12])[CH3:9])=[CH:4][N:3]=1.CC(C)([O-])C.[K+]>O1CCCC1>[Cl:1][C:2]1[N:3]=[C:4]2[N:13]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:11](=[O:12])[N:10]([C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][C:21]=3[F:28])[CH:8]([CH3:9])[C:5]2=[CH:6][N:7]=1

Participants

4

Reactant 2

HCID 21946011(+/-)-1-[1-(2-Chloro-pyrimidin-5-yl)-ethyl]-1-(2-fluoro-4-methoxy-phenyl)-3-phenyl-ureaHCID 23665647Potassium tert-butoxide2×

Product 1

HCID 10431009(+/-)-7-chloro-3-(2-fluoro-4-methoxy-phenyl)-4-methyl-1-phenyl-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

This urea was suspended in freshly distilled tetrahydrofuran (3 mL) and cooled in an ice-brine bath. Potassium tert-butoxide (1.0 M in tetrahydrofuran; 0.64 mL; 0.64 mmol) (Aldrich) was added dropwise to the suspension over 5 minutes. The solid went into solution as the potassium tert-butoxide was added. After stirring for an additional 15 minutes in the cold, the reaction mixture was filtered through a bed of silica gel (1.75 g), eluting with 1:1 ethyl acetate-hexanes and then ethyl acetate. Purification by flash chromatography (Biotage 40S; 40:60 to 50:50 ethyl acetate-hexanes) gave (±)-7-chloro-3-(2-fluoro-4-methoxy-phenyl)-4-methyl-1-phenyl-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one. (Yield 0.22 g; 38% overall for two steps).

Workup

  1. temperaturecooled in an ice-brine bath
  2. additionwas added
  3. filtrationwas filtered through a bed of silica gel (1.75 g)
  4. washeluting with 1:1 ethyl acetate-hexanes
  5. customPurification by flash chromatography (Biotage 40S; 40:60 to 50:50 ethyl acetate-hexanes)

Sources & evidence

ORD record
ord-735782dea91b404b8b94b4d7fa425fd8
Source dataset
uspto-grants-2006_09
Patent number
US07112676B2

Reaction notes

Loading…