Pyridine → Phenyl 2-fluoro-4-(3-oxo-3,4-dihydropyrido[3,2-b]pyrazin-8-yloxy)phenylcarbamate

HRID 217872Notes

Reaction equation

HRID 217872 reaction equation
N1C=CC=CC=1.[NH2:7][C:8]1[CH:25]=[CH:24][C:11]([O:12][C:13]2[C:22]3[N:21]=[CH:20][C:19](=[O:23])[NH:18][C:17]=3[N:16]=[CH:15][CH:14]=2)=[CH:10][C:9]=1[F:26].Cl[C:28]([O:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:29]>C1COCC1>[F:26][C:9]1[CH:10]=[C:11]([O:12][C:13]2[C:22]3[N:21]=[CH:20][C:19](=[O:23])[NH:18][C:17]=3[N:16]=[CH:15][CH:14]=2)[CH:24]=[CH:25][C:8]=1[NH:7][C:28](=[O:29])[O:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 15891Phenyl chloroformateHCID 469009328-(4-amino-3-fluorophenoxy)pyrido[2,3-b]pyrazin-3(4H)-one

Product 1

HCID 59588837Phenyl 2-fluoro-4-(3-oxo-3,4-dihydropyrido[3,2-b]pyrazin-8-yloxy)phenylcarbamate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Dry pyridine (125 μL, 1.55 mmol) was added to a suspension of 8-(4-amino-3-fluorophenoxy)pyrido[2,3-b]pyrazin-3(4H)-one (307 mg, 1.13 mmol) in dry THF (20 mL) under Ar and the mixture was cooled to 0° C. Phenyl chloroformate (170 μL, 1.35 mmol) was added dropwise over 5 min and the light brown mixture was stirred at 0° C. for an additional 5 min whereafter the mixture was allowed to warm up to RT and was stirred for 150 min. The brownish mixture was concentrated to dryness and the resulting residue was diluted with EtOAc (60 mL) and H2O (30 mL). The organic layer was isolated and filtered (80 mg of impure product) and the filtrate was washed with aqueous saturated NaHCO3 and brine. The organic layer was evaporated to dryness, re-dissolved in CH2Cl2 and chromatographed on a Biotage 25+M column, eluting with 20%→100% EtOAc in CH2Cl2 to give the title compound as a white solid. Yield: 280 mg (81%).

Workup

  1. temperatureto warm up to RT
  2. stirringwas stirred for 150 min
  3. concentrationThe brownish mixture was concentrated to dryness
  4. additionthe resulting residue was diluted with EtOAc (60 mL) and H2O (30 mL)
  5. customThe organic layer was isolated
  6. filtrationfiltered (80 mg of impure product)
  7. washthe filtrate was washed with aqueous saturated NaHCO3 and brine
  8. customThe organic layer was evaporated to dryness
  9. dissolutionre-dissolved in CH2Cl2
  10. customchromatographed on a Biotage 25+M column
  11. washeluting with 20%→100% EtOAc in CH2Cl2

Sources & evidence

ORD record
ord-407ef8c2b3ea4592a8733fb5033a9fa2
Source dataset
uspto-grants-2012_06
Patent number
US08198279B2

Reaction notes

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