(1-Bromoethyl)benzene → HCID 67224035, compound

HRID 1944765Notes

Reaction equation

HRID 1944765 reaction equation
[H-].[Na+].[CH2:3]([O:5][C:6]1[CH:11]=[CH:10][C:9]([S:12]([NH:15][CH:16]2[CH2:27][CH2:26][C:19]3([N:23]=[C:22]([CH3:24])[NH:21][C:20]3=[O:25])[CH2:18][CH2:17]2)(=[O:14])=[O:13])=[CH:8][C:7]=1[CH3:28])[CH3:4].Br[CH:30]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[CH3:31]>CN(C=O)C.C(=O)(O)[O-].[Na+]>[CH2:3]([O:5][C:6]1[CH:11]=[CH:10][C:9]([S:12]([NH:15][CH:16]2[CH2:17][CH2:18][C:19]3([N:23]=[C:22]([CH3:24])[N:21]([CH:30]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)[CH3:31])[C:20]3=[O:25])[CH2:26][CH2:27]2)(=[O:13])=[O:14])=[CH:8][C:7]=1[CH3:28])[CH3:4]

Participants

6

Reactant 3

HCID 11454(1-Bromoethyl)benzeneHCID 24758Sodium hydrideHCID 672248974-ethoxy-3-methyl-N-(2-methyl-4-oxo-1,3-diazaspiro[4.5]dec-1-en-8-yl)benzenesulfonamide

Product 1

HCID 67224035HCID 67224035, compoundYield 55%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

Sodium hydride (4.74 mg, 0.119 mmol) was added at room temperature to 4-ethoxy-3-methyl-N-(2-methyl-4-oxo-1,3-diazaspiro[4.5]dec-1-en-8-yl)benzenesulfonamide (Example 471, 30 mg, 0.079 mmol) in DMF (988 μl). The reaction was stirred five minutes then a solution of (1-bromoethyl)benzene (16.18 μl, 0.119 mmol) in 200 ul DMF was added and the reaction stirred overnight at room temperature. After 16 hours, LCMS and HPLC indicated approximately 4:1 product:smarting material. The reaction was diluted with saturated sodium bicarbonate and extracted with multiple volumes ethyl acetate. The combined organics were rinsed 1× brine and dried over sodium sulfate. TLC (ethyl acetate) gave a product Rf 0.38 and starting material on the baseline. The crude was chromatographed on Biotage 12S by manual step gradient 7-100% EtOAc/heptane to yield the product as an off-white solid (21 mg). LCMS [M+H]=484.2.

Workup

  1. stirringthe reaction stirred overnight at room temperature
  2. waitAfter 16 hours
  3. extractionextracted with multiple volumes ethyl acetate
  4. washThe combined organics were rinsed 1× brine
  5. dry with materialdried over sodium sulfate
  6. customTLC (ethyl acetate) gave a product Rf 0.38
  7. customThe crude was chromatographed on Biotage 12S by manual step gradient 7-100% EtOAc/heptane

Sources & evidence

ORD record
ord-ad92ea0b6f814fae8ba8d6e76892fe6c
Source dataset
uspto-grants-2013_03
Patent number
US08394858B2

Reaction notes

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