Potassium tert-butoxide → 6-chloro-2-[2-(2,5-difluoro-phenyl)-ethoxymethyl]-3H-pyrido[2,3-d]pyrimidin-4-one

HRID 2100480Notes

Reaction equation

HRID 2100480 reaction equation
CC([O-])(C)C.[K+].Cl[C:8]1[N:30]=[CH:29][C:28]([Cl:31])=[CH:27][C:9]=1[C:10]([NH:12][C:13](=[NH:26])[CH2:14][O:15][CH2:16][CH2:17][C:18]1[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=1[F:25])=[O:11]>CS(C)=O>[Cl:31][C:28]1[CH:29]=[N:30][C:8]2[N:26]=[C:13]([CH2:14][O:15][CH2:16][CH2:17][C:18]3[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=3[F:25])[NH:12][C:10](=[O:11])[C:9]=2[CH:27]=1

Participants

4

Reactant 2

HCID 23665647Potassium tert-butoxide2×HCID 1405200772,5-dichloro-N-[2-[2-(2,5-difluorophenyl)ethoxy]ethanimidoyl]pyridine-3-carboxamide

Product 1

HCID 1358991806-chloro-2-[2-(2,5-difluoro-phenyl)-ethoxymethyl]-3H-pyrido[2,3-d]pyrimidin-4-oneYield 9,200%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
50 °C

Procedure

KOtBu (28 mg, 250 μmol) was added at ambient temperature to a solution of 2,5-dichloro-N-{2-[2-(2,5-difluoro-phenyl)-ethoxy]-1-imino-ethyl}-nicotinamide (97 mg, 250 μmol) in DMSO (1 ml). The solution was stirred for 1 h at 50° C., cooled to ambient temperature, KOtBu (28 mg, 250 μmol) was added and the reaction solution was stirred at 50° C. for 14 h. The mixture was poured onto isopropyl acetate/ice water 1/1. The layers were separated and the aqueous layer was extracted two times with isopropyl acetate. The combined extracts were washed three times with brine and dried over sodium sulfate. The solvent was removed under reduced pressure to leave a yellow solid which was recrystallized from dichloromethane/heptane to give 6-chloro-2-[2-(2,5-difluoro-phenyl)-ethoxymethyl]-3H-pyrido[2,3-d]pyrimidin-4-one (8 mg, 23 mmol; 9%) as yellow crystals. MS: m/e=352.3 [M+H+].

Workup

  1. temperaturecooled to ambient temperature
  2. stirringthe reaction solution was stirred at 50° C. for 14 h
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted two times with isopropyl acetate
  5. washThe combined extracts were washed three times with brine
  6. dry with materialdried over sodium sulfate
  7. customThe solvent was removed under reduced pressure
  8. customto leave a yellow solid which
  9. customwas recrystallized from dichloromethane/heptane

Sources & evidence

ORD record
ord-cfbd32701e2846679bf359bcdc9a36ee
Source dataset
uspto-grants-2009_08
Patent number
US07572801B2

Reaction notes

Loading…