N-Fluorobenzenesulfonimide → 4-Chloro-5-fluoro-7H-pyrrolo(2,3-d)pyrimidine

HRID 221293

Reaction equation

HRID 221293 reaction equation
[Cl:1][C:2]1[C:3]2[C:10](Br)=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Li]CCCC.[B-](F)(F)(F)[F:18].[B-](F)(F)(F)F.C1[N+]2(O)CC[N+](F)(CC2)C1.C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)F)(=O)=O)=CC=1>C1COCC1>[Cl:1][C:2]1[C:3]2[C:10]([F:18])=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1

Participants

6

Reactant 4

HCID 588007N-FluorobenzenesulfonimideHCID 27373291-Fluoro-4-hydroxy-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate)HCID 53807105-Bromo-4-chloro-7H-pyrrolo[2,3-d]pyrimidineHCID 178418339Butyllithium

Product 1

HCID 113212244-Chloro-5-fluoro-7H-pyrrolo(2,3-d)pyrimidine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 4-chloro-5-bromo-7H-pyrrolo[2,3-d]pyrimidine (800 mg, 3.45 mmol) in THF (50 mL) at −78° C. was treated with n-BuLi (1.6 M in hexane, 2.2 eq, 7.6 mmol, 4.7 mL) dropwise, and stirred for 30 minutes at the same temperature. The mixture was treated with a solution of ACCUFLUOR® NFSi (2.0 eq, 7 mmol, 2.2 g) in THF (10 mL). The reaction mixture was allowed to warm to room temperature, was stirred for 10 h, and then concentrated to dryness. The residue was dissolved in EtOAc (100 mL), washed with water (3×15 mL) and brine (15 mL), dried with Na2SO4, and purified by reverse phase HPLC (10×250 mm C18 Luna column, 4.7 mL/min, 10-90% acetonitrile in water over 20 min) to provide intermediate compound 1. ESI-MS m/z=172.1 (MH+).

Workup

  1. stirringwas stirred for 10 h
  2. concentrationconcentrated to dryness
  3. dissolutionThe residue was dissolved in EtOAc (100 mL)
  4. washwashed with water (3×15 mL) and brine (15 mL)
  5. dry with materialdried with Na2SO4
  6. custompurified by reverse phase HPLC (10×250 mm C18 Luna column, 4.7 mL/min, 10-90% acetonitrile in water over 20 min)

Sources & evidence

ORD record
ord-b2208915e10544eab075d3ea59de5883
Source dataset
uspto-grants-2012_06
Patent number
US08207153B2

Linked notes

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