7-bromo-4-chloro-5H-pyrrolo[3,2-d]pyrimidine → HCID 24958369, compound

HRID 244454Notes

Reaction equation

HRID 244454 reaction equation
Br[C:2]1[C:6]2[N:7]=[CH:8][N:9]=[C:10]([Cl:11])[C:5]=2[NH:4][CH:3]=1.[Li]C(C)(C)C.[F:17][C:18]([F:38])([F:37])[C:19]([C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[N:26]([C:30]1[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=1)[N:25]=[CH:24]2)=[O:20]>C1COCC1>[Cl:11][C:10]1[C:5]2[NH:4][CH:3]=[C:2]([C:19]([C:21]3[CH:22]=[C:23]4[C:27](=[CH:28][CH:29]=3)[N:26]([C:30]3[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=3)[N:25]=[CH:24]4)([OH:20])[C:18]([F:37])([F:17])[F:38])[C:6]=2[N:7]=[CH:8][N:9]=1

Participants

5

Reactant 3

HCID 529876607-bromo-4-chloro-5H-pyrrolo[3,2-d]pyrimidineHCID 579432692,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanoneHCID 178418306HCID 178418306, compound

Product 1

HCID 24958369HCID 24958369, compoundYield 33.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a chilled (−78° C.) solution of 7-bromo-4-chloro-5H-pyrrolo[3,2-d]pyrimidine (80 mg, 0.34 mmol, 1 equiv.) in 5 mL of THF was added tert-BuLi (1.7 M in pentane, 0.43 mL, 0.73 mmol, 2.1 equiv.) dropwise. After 5 minutes, a chilled (−78° C.) solution of 2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanone (106 mg, 0.34 mmol, 1 equiv.) in 1 mL of THF was added in one portion. After 15 minutes, the reaction was quenched with 15 mL of water, warmed to room temperature, diluted with 100 mL of saturated aqueous ammonium chloride, and then extracted with EtOAc. The combined organic layers were dried, filtered, and concentrated in vacuo. The residue was dissolved in DMF and purified by reverse phase HPLC (5-95% CH3CN/water+0.1% TFA). The major fractions collected were made basic with saturated NaHCO3 and the CH3CN was concentrated in vacuo. The aqueous was extracted with EtOAc and washed with brine. The organic layers were dried, filtered, and concentrated in vacuo to provide 52 mg (32%) of the title compound as a white solid. MS m/z 462.56 (MH+).

Workup

  1. additionwas added in one portion
  2. waitAfter 15 minutes
  3. customthe reaction was quenched with 15 mL of water
  4. additiondiluted with 100 mL of saturated aqueous ammonium chloride
  5. extractionextracted with EtOAc
  6. customThe combined organic layers were dried
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. dissolutionThe residue was dissolved in DMF
  10. custompurified by reverse phase HPLC (5-95% CH3CN/water+0.1% TFA)
  11. customThe major fractions collected
  12. concentrationthe CH3CN was concentrated in vacuo
  13. extractionThe aqueous was extracted with EtOAc
  14. washwashed with brine
  15. customThe organic layers were dried
  16. filtrationfiltered
  17. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-307a79f40e4d4df28c688b352e752bdc
Source dataset
uspto-grants-2014_02
Patent number
US08658637B2

Reaction notes

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