N-Fluorobenzenesulfonimide → 3-chloro-N-[3-fluoro-6-methyl-2-(1H-pyrazol-4-yl)thieno[2,3-b]pyridin-4-yl]benzenesulfonamide

HRID 573673Notes

Reaction equation

HRID 573673 reaction equation
Br[C:2]1[C:10]2[C:5](=[N:6][C:7]([CH3:22])=[CH:8][C:9]=2[NH:11][S:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[CH:16]=2)(=[O:14])=[O:13])[S:4][C:3]=1[C:23]1[CH:24]=[N:25][NH:26][CH:27]=1.[Li]CCCC.C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:43])(=O)=O)=CC=1>C1COCC1>[Cl:21][C:17]1[CH:16]=[C:15]([S:12]([NH:11][C:9]2[CH:8]=[C:7]([CH3:22])[N:6]=[C:5]3[S:4][C:3]([C:23]4[CH:24]=[N:25][NH:26][CH:27]=4)=[C:2]([F:43])[C:10]=23)(=[O:14])=[O:13])[CH:20]=[CH:19][CH:18]=1

Participants

5

Reactant 3

HCID 588007N-FluorobenzenesulfonimideHCID 68324082N-[3-bromo-6-methyl-2-(1H-pyrazol-4-yl)thieno[2,3-b]pyridin-4-yl]-3-chlorobenzenesulfonamideHCID 178418339Butyllithium

Product 1

HCID 683241583-chloro-N-[3-fluoro-6-methyl-2-(1H-pyrazol-4-yl)thieno[2,3-b]pyridin-4-yl]benzenesulfonamideYield 4.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A stirred solution of N-[3-bromo-6-methyl-2-(1H-pyrazol-4-yl)thieno[2,3-b]pyridin-4-yl]-3-chlorobenzenesulfonamide (Example 100) (120 mg, 0.248 mmol) in THF (1.5 mL) was cooled to −78° C. using a dry ice/acetone bath. n-BuLi (2.5M in Hexane) (0.109 mL, 0.273 mmol) was added dropwise and the mixture stirred at −78° C. for ca. 1.5 h. Then, N-fluorobenzenesulfonimide (82 mg, 0.260 mmol), pre-dissolved in THF (0.5 mL), was added dropwise and the mixture stirred at −78° C. for ca. 1 h and then left to stir at RT for 3 days (ca. 89 h). The reaction mixture was then quenched with saturated NH4Cl solution (ca. 20 mL), extracted with ethyl acetate (20 mL×3) and the combined organics dried and concentrated. The residue was purified by normal phase chromatography, eluting with a gradient of 0-100% ethyl acetate in DCM and further purified by MDAP (acidic conditions), to give the title compound (5 mg). LCMS (A) m/z: 423 [M+1]+, Rt 1.20 min (acidic).

Workup

  1. additionwas added dropwise
  2. stirringthe mixture stirred at −78° C. for ca. 1 h
  3. waitleft
  4. stirringto stir at RT for 3 days (ca. 89 h)
  5. customThe reaction mixture was then quenched with saturated NH4Cl solution (ca. 20 mL)
  6. extractionextracted with ethyl acetate (20 mL×3)
  7. customthe combined organics dried
  8. concentrationconcentrated
  9. customThe residue was purified by normal phase chromatography
  10. washeluting with a gradient of 0-100% ethyl acetate in DCM
  11. customfurther purified by MDAP (acidic conditions)

Sources & evidence

ORD record
ord-b7ea4b99ce8a49db85ce810c7bbe61c6
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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