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

HRID 1692132Notes

Reaction equation

HRID 1692132 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[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=2[C:25]([NH:27][NH2:28])=O)(=[O:16])=[O:15])=[CH:10][CH:9]=1)([CH3:7])([CH3:6])[CH3:5].C(=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:20]=[C:21]([Cl:24])[CH:22]=[CH:23][C:18]=2[NH:17][S:14]([C:11]2[CH:12]=[CH:13][C:8]([C:4]([CH3:7])([CH3:6])[CH3:5])=[CH:9][CH:10]=2)(=[O:16])=[O:15])=[N:27][N:28]=1

Participants

7

Reactant 4

HCID 6363IsopropylamineHCID 10476Cyanogen BromideHCID 11430Potassium CarbonateHCID 593029884-tert-butyl-N-(4-chloro-2-hydrazinocarbonyl-phenyl)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 (111 mg, 1.05 mmol) was added to a solution of 4-tert-butyl-N-(4-chloro-2-hydrazinocarbonyl-phenyl)-benzenesulfonamide (200 mg, 0.524 mmol) and potassium carbonate (145 mg, 1.05 mmol) in dioxane (2 mL) and the reaction was stirred for 18 h at room temperature. Isopropyl amine (0.18 mL, 2.09 mmol) and acetic acid (0.15 mL) were added and the reaction was heated at 135° C. for an additional 18 h. The resultant solution was partitioned between ethyl acetate/water and 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 finally purified by flash column chromatography (10-100% ethyl acetate and hexane) then preparative HPLC (10-90% gradient of MeCN-water) to afford the title compound as a white solid: MS (ES) M+H expected 448.2, found 448.1.

Workup

  1. temperaturethe reaction was heated at 135° C. for an additional 18 h
  2. customThe resultant solution was partitioned between ethyl acetate/water
  3. washthe organic phase was washed with 1N HCl, saturated sodium bicarbonate, and brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe crude product was finally purified by flash column chromatography (10-100% ethyl acetate and hexane)

Sources & evidence

ORD record
ord-1c44fe10e66a424ba8d150a1a8ee1048
Source dataset
uspto-grants-2012_04
Patent number
US08153818B2

Reaction notes

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