Carbon Dioxide → 1-chloro-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)isoquinoline-6-sulfonamide

HRID 1473322Notes

Reaction equation

HRID 1473322 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(=O)=O.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Cl:31][C:32]1[C:41]2[C:36](=[CH:37][C:38]([S:42](Cl)(=[O:44])=[O:43])=[CH:39][CH:40]=2)[CH:35]=[CH:34][N:33]=1>C1COCC1.CC(C)=O>[Cl:31][C:32]1[C:41]2[C:36](=[CH:37][C:38]([S:42]([N:6]([CH2:5][C:4]3[CH:12]=[CH:13][C:14]([O:16][CH3:17])=[CH:15][C:3]=3[O:2][CH3:1])[C:7]3[S:11][N:10]=[CH:9][N:8]=3)(=[O:44])=[O:43])=[CH:39][CH:40]=2)[CH:35]=[CH:34][N:33]=1

Participants

7

Reactant 4

HCID 280Carbon DioxideHCID 2733832Lithium HexamethyldisilazideHCID 57732216N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amineHCID 861938101-Chloroisoquinoline-6-sulfonyl chloride

Product 1

HCID 866873751-chloro-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)isoquinoline-6-sulfonamideYield 36.3%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A 250 mL round bottom flask was charged with N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amine (2.291 g, 9.12 mmol) and THF (45.6 mL). The resulting mixture was cooled in a dry ice and acetone bath for 10 min. To this solution was added lithium bis(trimethylsilyl)amide (13.68 mL, 13.68 mmol) dropwise over 30 seconds. The ice bath was removed for 10 minutes and then the flask was returned to the bath for an additional 5 minutes. A solution of 1-chloroisoquinoline-6-sulfonyl chloride (2.39 g, 9.12 mmol) in 7 mL of THF was then added dropwise over 5 minutes. The ice bath was removed and the resulting mixture stirred for 30 minutes. LC/MS indicated that the desired product was generated. The reaction mixture was concentrated, taken up in minimal DCM, loaded onto a cartridge and purified by silica gel chromatography (330 g), using 0 to 30% Heptane: EtOAc. Fractions containing the product were combined and concentrated to afford (1-chloro-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)isoquinoline-6-sulfonamide (1.58 g, 3.31 mmol) as a white solid.

Workup

  1. customThe ice bath was removed for 10 minutes
  2. customThe ice bath was removed
  3. concentrationThe reaction mixture was concentrated
  4. custompurified by silica gel chromatography (330 g)
  5. additionFractions containing the product
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-704ae9fbbc96444e82b7259e6afb3687
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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