5-Chlorothiophene-2-sulfonyl chloride → HCID 58054553, compound

HRID 1808591Notes

Reaction equation

HRID 1808591 reaction equation
[NH2:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[C:11]#[N:12])[N:4]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[N:3]=1.[Cl:20][C:21]1[S:25][C:24]([S:26](Cl)(=[O:28])=[O:27])=[CH:23][CH:22]=1>ClCCl.N1C=CC=CC=1>[Cl:20][C:21]1[S:25][C:24]([S:26]([N:1]([S:26]([C:24]2[S:25][C:21]([Cl:20])=[CH:22][CH:23]=2)(=[O:28])=[O:27])[C:2]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][C:9]=3[C:11]#[N:12])[N:4]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[N:3]=2)(=[O:28])=[O:27])=[CH:23][CH:22]=1

Participants

5

Reactant 2

HCID 27339255-Chlorothiophene-2-sulfonyl chloride2×HCID 58054554HCID 58054554, compound

Product 1

HCID 58054553HCID 58054553, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
45 °C

Procedure

1,1-Dimethylethyl 3-amino-4-cyano-1H-indazole-1-carboxylate (for a preparation see Intermediate 63) (4.3 g, 16.65 mmol) was dissolved in a mixture of dichloromethane (40 mL) and pyridine (40 mL). 5-Chloro-2-thiophenesulfonyl chloride (7.23 g, 33.3 mmol) was added to the solution and it was stirred at 45° C. under nitrogen for 60 h. LCMS showed approx 30% starting material remaining, so further quantity of 5-chloro-2-thiophenesulfonyl chloride (3.5 g, 16.12 mmol) was added to the reaction, and the mixture was stirred for 2 h. LCMS showed no change in product so the reaction was concentrated under vacuo. The residue was dissolved in DCM (200 mL) and washed 3 times with water (200 mL). The organic layer was dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue (10 g) was dissolved in DCM and loaded onto a 750 g silica column and purified by chromatography on the Companion system using a 0-25% ethyl acetate-DCM gradient. Appropriate fractions were evaporated in vacuo to give the title compound (5.8 g, 56%) as an orange solid. LCMS (System A) RT=1.45 min, ES+ve m/z 636/638 (M+NH4)+.

Workup

  1. stirringthe mixture was stirred for 2 h
  2. concentrationwas concentrated under vacuo
  3. dissolutionThe residue was dissolved in DCM (200 mL)
  4. washwashed 3 times with water (200 mL)
  5. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  6. customevaporated in vacuo
  7. dissolutionThe residue (10 g) was dissolved in DCM
  8. custompurified by chromatography on the Companion system
  9. customAppropriate fractions were evaporated in vacuo

Sources & evidence

ORD record
ord-a88016aafc364e90a5e43c719a467fc6
Source dataset
uspto-grants-2013_01
Patent number
US08357716B2

Reaction notes

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