Potassium tert-butoxide → (+/-)-3-[7-chloro-3-(2-fluoro-4-methoxy-phenyl)-4-methyl-2-oxo-3,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-1-yl]-benzonitrile

HRID 2216976Notes

Reaction equation

HRID 2216976 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH:8]([N:10]([C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][C:23]=2[F:30])[C:11]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20]#[N:21])[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]=[C:16]([CH:17]=[CH:18][CH:19]=3)[C:20]#[N:21])[C:11](=[O:12])[N:10]([C:22]3[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][C:23]=3[F:30])[CH:8]([CH3:9])[C:5]2=[CH:6][N:7]=1

Participants

4

Reactant 2

HCID 23665647Potassium tert-butoxideHCID 86597435(+/-)-1-[1-(2-Chloro-pyrimidin-5-yl)-ethyl]-3-(3-cyano-pheny)-1-(2-fluoro-4-methoxy-phenyl)-urea

Product 1

HCID 10047943(+/-)-3-[7-chloro-3-(2-fluoro-4-methoxy-phenyl)-4-methyl-2-oxo-3,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-1-yl]-benzonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

This urea was suspended in freshly distilled tetrahydrofuran (10 mL) and cooled in an ice-brine bath. Potassium tert-butoxide (1.0 M in tetrahydrofuran; 2.70 mL; 2.70 mmol) (Aldrich) was added dropwise to the suspension over 8 minutes. The reaction mixture was stirred for an additional 15 minutes in the cold and then filtered through a bed of silica gel (7–8 g), eluting with 1:1 ethyl acetate-hexanes and then ethyl acetate. Purification by flash chromatography (Biotage 40M; 40:60 to 50:50 ethyl acetate-hexanes) gave (±)-3-[7-chloro-3-(2-fluoro-4-methoxy-phenyl)-4-methyl-2-oxo-3,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-1-yl]-benzonitrile as a white solid. (Yield 1.11 g; 66.8% overall for two steps).

Workup

  1. temperaturecooled in an ice-brine bath
  2. filtrationthen filtered through a bed of silica gel (7–8 g)
  3. washeluting with 1:1 ethyl acetate-hexanes
  4. customPurification by flash chromatography (Biotage 40M; 40:60 to 50:50 ethyl acetate-hexanes)

Sources & evidence

ORD record
ord-d9dae0a8f4ae412796d9ae6384b2092a
Source dataset
uspto-grants-2006_09
Patent number
US07112676B2

Reaction notes

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