Ethyl 6-amino-2-chloro-5-nitropyrimidine-4-carboxylate → HCID 66614187, compound

HRID 510054Notes

Reaction equation

HRID 510054 reaction equation
F[C:2]1[CH:3]=[C:4]2[C:10](I)=[N:9][N:8]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[F:19])[C:5]2=[N:6][CH:7]=1.CCCC[Sn](CCCC)CCCC.CCCC[Sn](CCCC)CCCC.[NH2:46][C:47]1[N:52]=[C:51](Cl)[N:50]=[C:49]([C:54]([O:56][CH2:57][CH3:58])=[O:55])[C:48]=1[N+:59]([O-:61])=[O:60]>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:46][C:47]1[N:52]=[C:51]([C:10]2[C:4]3[C:5](=[N:6][CH:7]=[CH:2][CH:3]=3)[N:8]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[F:19])[N:9]=2)[N:50]=[C:49]([C:54]([O:56][CH2:57][CH3:58])=[O:55])[C:48]=1[N+:59]([O-:61])=[O:60]

Participants

6

Reactant 3

HCID 4390083Ethyl 6-amino-2-chloro-5-nitropyrimidine-4-carboxylateHCID 6327815HexabutyldistannaneHCID 580656025-Fluoro-1-(2-fluorobenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridine

Product 1

HCID 66614187HCID 66614187, compound

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Under argon, 3.85 g (10.91 mmol) of the compound from example 24A were initially charged in dioxane (100 ml) and the reaction mixture was purged with argon. Subsequently, 8.27 ml (16.36 mmol) of hexabutylditin and 2.96 g (12.00 mmol) of ethyl 6-amino-2-chloro-5-nitropyrimidine-4-carboxylate (prepared according to J. Chem. Res. 1989, 2086-2097) were added. Thereafter, 3.83 g (5.45 mmol) of bis(triphenylphosphine)palladium(II) chloride were added and the reaction mixture was stirred at 100° C. overnight. Thereafter, the mixture was cooled to RT and filtered through Celite, and the residue was washed with methanol. The filtrate was concentrated, and the residue was extracted by stirring with ethyl acetate and filtered off. The filtrate was concentrated and the residue was purified by means of prep. HPLC (eluent: acetonitrile/water with 0.1% formic acid gradient). This gave 1.36 g (71% purity, 14% of theory) of crude product, which was converted without further purification.

Workup

  1. customthe reaction mixture was purged with argon
  2. temperatureThereafter, the mixture was cooled to RT
  3. filtrationfiltered through Celite
  4. washthe residue was washed with methanol
  5. concentrationThe filtrate was concentrated
  6. extractionthe residue was extracted
  7. stirringby stirring with ethyl acetate
  8. filtrationfiltered off
  9. concentrationThe filtrate was concentrated
  10. customthe residue was purified by means of prep
  11. customThis gave 1.36 g (71% purity, 14% of theory) of crude product, which was converted without further purification

Sources & evidence

ORD record
ord-60ec768fa4434d84970c61afd5162e51
Source dataset
uspto-grants-2015_08
Patent number
US09096592B2

Reaction notes

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