Pyridine → 4-tert-Butyl-N-{4-chloro-2-[4-methyl-5-(5-methyl-oxazol-4-yl)-4H-[1,2,4]triazol-3-yl]-phenyl}-benzenesulfonamide

HRID 1692130Notes

Reaction equation

HRID 1692130 reaction equation
[CH3:1][NH:2][C:3]([C:5]1[N:6]=[CH:7][O:8][C:9]=1[CH3:10])=O.N1C=CC=CC=1.[C:17]([C:21]1[CH:26]=[CH:25][C:24]([S:27]([NH:30][C:31]2[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][C:32]=2[C:38]([NH:40][NH2:41])=O)(=[O:29])=[O:28])=[CH:23][CH:22]=1)([CH3:20])([CH3:19])[CH3:18]>ClCCl>[C:17]([C:21]1[CH:26]=[CH:25][C:24]([S:27]([NH:30][C:31]2[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][C:32]=2[C:38]2[N:2]([CH3:1])[C:3]([C:5]3[N:6]=[CH:7][O:8][C:9]=3[CH3:10])=[N:41][N:40]=2)(=[O:28])=[O:29])=[CH:23][CH:22]=1)([CH3:18])([CH3:19])[CH3:20]

Participants

5

Reactant 3

HCID 1049PyridineHCID 593029884-tert-butyl-N-(4-chloro-2-hydrazinocarbonyl-phenyl)benzenesulfonamideHCID 59303069N,5-Dimethyloxazole-4-carboxamide

Product 1

HCID 593030164-tert-Butyl-N-{4-chloro-2-[4-methyl-5-(5-methyl-oxazol-4-yl)-4H-[1,2,4]triazol-3-yl]-phenyl}-benzenesulfonamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-40 °C

Procedure

A vial was charged with 5-methyl-oxazole-4-carboxylic acid methylamide (71 mg, 0.5 mmol), pyridine (0.12 mL, 1.5 mmol), and anhydrous dichloromethane (2.5 mL). The reaction vessel was cooled to −40° C. and trifluoromethanesulfonyl anhydride (0.11 mL, 0.65 mmol) was added. The reaction was subsequently warmed to −10° C. over 2.5 h and then 4-tert-butyl-N-(4-chloro-2-hydrazinocarbonyl-phenyl)-benzenesulfonamide (191 mg, 0.5 mmol) was added. The reaction was warmed to room temperature stirred an additional 2 h. The solvent was concentrated in vacuo and ethanol (5 mL) and diisopropylamine (0.5 mL) were added and the solution stirred at 90° C. overnight. The following day, the reaction was concentrated in vacuo and the crude material was purified by flash column chromatography (10-100% ethyl acetate and hexane), followed by preparative HPLC (10-90% gradient of MeCN-water) to yield the title compound: MS (ES) M+H expected 486.1, found 486.0.

Workup

  1. temperatureThe reaction was subsequently warmed to −10° C. over 2.5 h
  2. temperatureThe reaction was warmed to room temperature
  3. concentrationThe solvent was concentrated in vacuo and ethanol (5 mL) and diisopropylamine (0.5 mL)
  4. additionwere added
  5. stirringthe solution stirred at 90° C. overnight
  6. concentrationThe following day, the reaction was concentrated in vacuo
  7. customthe crude material was purified by flash column chromatography (10-100% ethyl acetate and hexane)

Sources & evidence

ORD record
ord-319c0897ccd046f38a876fedc6bf3dc8
Source dataset
uspto-grants-2012_04
Patent number
US08153818B2

Reaction notes

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