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

HRID 1473322노트

반응식

HRID 1473322 반응식
[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

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 180Acetone용매HCID 8028Tetrahydrofuran용매2회

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-704ae9fbbc96444e82b7259e6afb3687
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09012443B2

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