2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanone → 1-(5-Allyl-4-chloro-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanol

HRID 244450Notes

Reaction equation

HRID 244450 reaction equation
[CH2:1]([N:4]1[C:12]2[C:11]([Cl:13])=[N:10][CH:9]=[N:8][C:7]=2[C:6](Br)=[CH:5]1)[CH:2]=[CH2:3].[Li]CCCC.[F:20][C:21]([F:41])([F:40])[C:22]([C:24]1[CH:25]=[C:26]2[C:30](=[CH:31][CH:32]=1)[N:29]([C:33]1[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=1)[N:28]=[CH:27]2)=[O:23]>C1COCC1.O.[Cl-].[Na+].O>[CH2:1]([N:4]1[C:12]2[C:11]([Cl:13])=[N:10][CH:9]=[N:8][C:7]=2[C:6]([C:22]([C:24]2[CH:25]=[C:26]3[C:30](=[CH:31][CH:32]=2)[N:29]([C:33]2[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=2)[N:28]=[CH:27]3)([OH:23])[C:21]([F:40])([F:20])[F:41])=[CH:5]1)[CH:2]=[CH2:3]

Participants

7

Reactant 3

HCID 579432692,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanoneHCID 594373185-allyl-7-bromo-4-chloro-5H-pyrrolo[3,2-d]pyrimidineHCID 178418339Butyllithium

Product 1

HCID 594371991-(5-Allyl-4-chloro-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanolYield 23.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

To a chilled (−78° C.) solution of 5-allyl-7-bromo-4-chloro-5H-pyrrolo[3,2-d]pyrimidine (570 mg, 2.1 mmol) in 10 mL of THF was added n-BuLi (2.5 M in THF, 1.5 mL, 2.5 mmol) dropwise. After 5 minutes, a chilled (−78° C.) solution of 2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanone (708 mg, 2.3 mmol) in 3 mL of THF was added in one portion. After 15 minutes, the mixture was diluted with water and warmed to room temperature, diluted with brine, and extracted with EtOAc. The combined organic layers were dried, filtered, and concentrated in vacuo. The residue was purified by flash chromatography using EtOAc-hexanes (15-60% gradient) to provide 245 mg (23%) of the title compound as a beige solid. MS m/z 502.23 (MH+).

Workup

  1. additionwas added in one portion
  2. waitAfter 15 minutes
  3. extractionextracted with EtOAc
  4. customThe combined organic layers were dried
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-70c6c1e6d7ac48ac96e605846f18b8f8
Source dataset
uspto-grants-2014_02
Patent number
US08658637B2

Reaction notes

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