Isopropylamine → N-[2-(5-Amino-4-isopropyl-4H-[1,2,4]triazol-3-yl)-4-chloro-phenyl]-4-tert-butyl-benzenesulfonamide

HRID 2094215Notes

Reaction equation

HRID 2094215 reaction equation
[N:1]#[C:2]Br.[C:4]([C:8]1[CH:13]=[CH:12][C:11]([S:14]([NH:17][C:18]2[C:19]([C:25]([NH:27][NH2:28])=O)=N[C:21]([Cl:24])=[CH:22][CH:23]=2)(=[O:16])=[O:15])=[CH:10][CH:9]=1)([CH3:7])([CH3:6])[CH3:5].[C:29](=O)([O-])[O-].[K+].[K+].[CH:35]([NH2:38])([CH3:37])[CH3:36]>O1CCOCC1.C(O)(=O)C>[NH2:1][C:2]1[N:38]([CH:35]([CH3:37])[CH3:36])[C:25]([C:19]2[CH:29]=[C:21]([Cl:24])[CH:22]=[CH:23][C:18]=2[NH:17][S:14]([C:11]2[CH:10]=[CH:9][C:8]([C:4]([CH3:5])([CH3:6])[CH3:7])=[CH:13][CH:12]=2)(=[O:16])=[O:15])=[N:27][N:28]=1

Participants

7

Reactant 4

HCID 6363IsopropylamineHCID 10476Cyanogen BromideHCID 11430Potassium CarbonateHCID 866183534-tert-butyl-N-(6-chloro-2-hydrazinocarbonyl-pyridin-3-yl)-benzenesulfonamide

Product 1

HCID 59302968N-[2-(5-Amino-4-isopropyl-4H-[1,2,4]triazol-3-yl)-4-chloro-phenyl]-4-tert-butyl-benzenesulfonamide

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 312751,4-DioxaneSolvent

Procedure

Cyanogen bromide (110.9 mg, 1.05 mmol) was added to a solution of 4-tert-butyl-N-(6-chloro-2-hydrazinocarbonyl-pyridin-3-yl)-benzenesulfonamide (200 mg, 0.524 mmol) and potassium carbonate (145 mg, 1.05 mmol) in dioxane (2 mL). The resultant mixture reaction was stirred for 18 h at room temperature. Isopropyl amine (0.18 mL, 2.09 mmol) and acetic acid (0.15 mL) were subsequently added and the reaction was heated at 135° C. for 18 h. The crude mixture was partitioned between ethyl acetate and water and the layers were separated. The organic phase was washed with 1N HCl, saturated sodium bicarbonate, and brine; dried over magnesium sulfate, and concentrated in vacuo. The crude product was subsequently purified via flash column chromatography (10-100% ethyl acetate and hexane) followed by preparative HPLC (10-90% gradient of MeCN-water) to afford the title compound as a white solid: MS (ES) M+H expected 449.1. found 449.2.

Workup

  1. temperaturethe reaction was heated at 135° C. for 18 h
  2. customThe crude mixture was partitioned between ethyl acetate and water
  3. customthe layers were separated
  4. washThe organic phase was washed with 1N HCl, saturated sodium bicarbonate, and brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe crude product was subsequently purified via flash column chromatography (10-100% ethyl acetate and hexane)

Sources & evidence

ORD record
ord-8ad9eeae150841bc809010fa191d5ea4
Source dataset
uspto-grants-2013_05
Patent number
US08445518B2

Reaction notes

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