N-Fluorobenzenesulfonimide → HCID 118036589, compound

HRID 1777856Notes

Reaction equation

HRID 1777856 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[N:10][C:11]=1[CH:12]([O:15][CH3:16])[O:13][CH3:14])[N:8]([C:17]([NH:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][N:21]=1)=[O:18])[CH2:7][CH2:6][CH2:5]2.[Li]CCCC.[F:35]N(S(C1C=CC=CC=1)(=O)=O)S(C1C=CC=CC=1)(=O)=O>C1COCC1>[CH3:14][O:13][CH:12]([O:15][CH3:16])[C:11]1[N:10]=[C:9]2[C:4]([CH2:5][CH2:6][CH2:7][N:8]2[C:17]([NH:19][C:20]2[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][N:21]=2)=[O:18])=[CH:3][C:2]=1[F:35]

Participants

5

Reactant 3

HCID 588007N-FluorobenzenesulfonimideHCID 118036953HCID 118036953, compound2×HCID 178418339Butyllithium

Product 1

HCID 118036589HCID 118036589, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 6-bromo-7-(dimethoxymethyl)-N-(5-(trifluoromethyl)pyridin-2-yl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide (intermediate 2D, 50 mg, 0.105 mmol) in THF (1 ml) at −78° C. under argon was treated drop wise with n-BuLi (1.5 M in hexane, 0.154 ml, 0.231 mmol). The resulting brown solution was stirred for 2 min, then a solution of N-fluoro-N-(phenylsulfonyl)benzenesulfonamide (80 mg, 0.254 mmol) in THF (0.5 ml) was added. The resulting yellow solution was stirred at −78° C. for 10 min. The reaction mixture was quenched by addition of sat. aq. NH4Cl, warmed to room temperature and extracted with EtOAc (2×). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by normal phase chromatography (12 g silica gel cartridge, heptanes/EtOAc 100:0 to 60:40) the product containing fractions were concentrated to give the title compound as a white solid. (UPLC-MS 1) tR 1.25 min; ESI-MS 415.1 [M+H]+.

Workup

  1. stirringThe resulting yellow solution was stirred at −78° C. for 10 min
  2. customThe reaction mixture was quenched by addition of sat. aq. NH4Cl
  3. extractionextracted with EtOAc (2×)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material was purified by normal phase chromatography (12 g silica gel cartridge, heptanes/EtOAc 100:0 to 60:40) the product
  9. additioncontaining fractions
  10. concentrationwere concentrated

Sources & evidence

ORD record
ord-8850ffbdc953441a964afd56f8f8b0d5
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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