Lithium bis(trimethylsilyl)amide → HCID 66652613, compound

HRID 509114Notes

Reaction equation

HRID 509114 reaction equation
[CH3:1][O:2][C:3]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:4]=1[CH2:5][NH:6][C:7]1[S:11][N:10]=[CH:9][N:8]=1.C[Si](C)(C)N[Si](C)(C)C.[Li].[Br:28][C:29]1[CH:34]=[CH:33][C:32]([S:35](Cl)(=[O:37])=[O:36])=[CH:31][C:30]=1[C:39]#[N:40]>O1CCCC1>[Br:28][C:29]1[CH:34]=[CH:33][C:32]([S:35]([N:6]([CH2:5][C:4]2[CH:12]=[CH:13][C:14]([O:16][CH3:17])=[CH:15][C:3]=2[O:2][CH3:1])[C:7]2[S:11][N:10]=[CH:9][N:8]=2)(=[O:36])=[O:37])=[CH:31][C:30]=1[C:39]#[N:40]

Participants

5

Reactant 3

HCID 57426343Lithium bis(trimethylsilyl)amideHCID 57732216N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amineHCID 866824824-broMo-2-cyanobenzene-1-sulfonyl chloride

Product 1

HCID 66652613HCID 66652613, compoundYield 100.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a nitrogen purged solution of N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amine (Preparation 18, 448 mg, 1.78 mmol) in tetrahydrofuran (7.5 mL) at −78° C. was added lithium hexamethyl disilazane (1.0 M in tetrahydrofuran, 1.96 mL). The reaction was stirred for 15 minutes before a solution of 4-bromo-3-cyanobenzenesulfonyl chloride (Preparation 27, 500 mg, 1.78 mmol) in tetrahydrofuran (7.5 mL) was added dropwise. The reaction mixture was warmed to room temperature and stirred for 3 hours. The reaction mixture was partitioned between water (10 mL) and ethyl acetate (3×10 mL). The combined organic extracts were washed with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to afford a yellow solid. The material was purified by silica gel column chromatography (ISCO™ companion, 40 g column, 0-30% ethyl acetate in heptane gradient elution). Fractions containing product were combined and concentrated in vacuo to obtain the title compound as a colourless solid (883 mg, 73%)

Workup

  1. additionwas added dropwise
  2. customThe reaction mixture was partitioned between water (10 mL) and ethyl acetate (3×10 mL)
  3. washThe combined organic extracts were washed with a saturated aqueous solution of sodium chloride
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto afford a yellow solid
  8. customThe material was purified by silica gel column chromatography (ISCO™ companion, 40 g column, 0-30% ethyl acetate in heptane gradient elution)
  9. additionFractions containing product
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-36a3c55d026640b68001655e95e486a1
Source dataset
uspto-grants-2015_08
Patent number
US09096558B2

Reaction notes

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