2-Chloro-4-(trifluoromethyl)benzenesulfonyl chloride → HCID 57585147, compound

HRID 2077609Notes

Reaction equation

HRID 2077609 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:21]=[CH:20][C:12]3[N:13]=[C:14]([NH:16]C(=O)C)[S:15][C:11]=3[CH:10]=2)[CH:5]=[N:6][C:7]=1[Cl:8].[Cl:22][C:23]1[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[CH:25][C:24]=1[S:33](Cl)(=[O:35])=[O:34]>N1C=CC=CC=1.CN(C1C=CN=CC=1)C.O.C(OCC)(=O)C>[NH2:16][C:14]1[S:15][C:11]2[CH:10]=[C:9]([C:4]3[CH:3]=[C:2]([NH:1][S:33]([C:24]4[CH:25]=[CH:26][C:27]([C:29]([F:30])([F:31])[F:32])=[CH:28][C:23]=4[Cl:22])(=[O:35])=[O:34])[C:7]([Cl:8])=[N:6][CH:5]=3)[CH:21]=[CH:20][C:12]=2[N:13]=1

Participants

7

Reactant 2

HCID 27366752-Chloro-4-(trifluoromethyl)benzenesulfonyl chlorideHCID 51355176HCID 51355176, compound

Product 1

HCID 57585147HCID 57585147, compound

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a 50 ml round-bottom flask equipped with a stirbar and charged with N-(6-(5-amino-6-chloropyridin-3-yl)benzo[d]thiazol-2-yl)acetamide (0.300 g, 0.9 mmol) in Pyridine (5 ml), was added DMAP (0.030 g, 0.2 mmol) and 2-chloro-4-(trifluoromethyl)benzene-1-sulfonyl chloride (1 g, 5 mmol). The flask was allowed to stir under inert atmosphere overnight. The progress of the reaction was monitored by LC/MS, which showed desired (N-Acyl, m/z=562) and bis-sulfonated material. The mixture was diluted with water (30 ml) and ethyl acetate and then allowed the mixture to stir 10 minutes. The organic layer was extracted with EtOAc (3×25 ml). Then combined organics, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was diluted with MeOH (6 ml), then added the mixture into two microwave vials equipped with stirbars (with the organics equally distributed). Potassium carbonate (0.300 g) was added to each vial, then capped and placed into a CEM Microwave for 10 minutes at 80° C., while 60 watts of energy was supplied via Powermax® (Simultaneous heating while cooling technology). The progress of the de-sulfonylation/de-acylation reaction was monitored by LC/MS, which showed mostly desired product. The two mixtures were combined and concentrated in vacuo. Water (30 ml) was added to the flask, along with a stirbar and then neutralized the mixture with 1N HCl. The precipitate was collected by filtration and washed with Hexanes. The solid was dissolved in ethyl acetate, and then purified the crude material by ISCO Silica-Gel Chromatography (120 gram column) in a gradient of 1-5% MeOH/DCM over 30 minutes. The fractions with desired product were combined and concentrated in vacuo. The residue was recrystallized from EtOAc/Hexanes to give N-(5-(2-aminobenzo[d]thiazol-6-yl)-2-chloropyridin-3-yl)-2-chloro-4-(trifluoromethyl)benzenesulfonamide (0.040 g, 8% yield) as a tan crystalline solid. MS (ESI pos. ion) m/z: 520 (MH+). Calc'd exact mass for C19H11Cl2F3N4O2S2: 519. 1H NMR (400 MHz, DMSO-d6): 7.38-7.44 (m, 1H), 7.49 (d, J=8.53 Hz, 1H), 7.68 (s, 2H), 7.89 (d, J=8.53 Hz, 1H), 7.99 (d, J=19.07 Hz, 2H), 8.12 (d, J=8.03 Hz, 1H), 8.58 (s, 1H).

Workup

  1. customTo a 50 ml round-bottom flask equipped with a stirbar
  2. stirringto stir 10 minutes
  3. extractionThe organic layer was extracted with EtOAc (3×25 ml)
  4. dry with materialThen combined organics, dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. additionThe residue was diluted with MeOH (6 ml)
  8. additionadded the mixture into two microwave vials
  9. customequipped with stirbars (with the organics
  10. additionPotassium carbonate (0.300 g) was added to each vial,
  11. customthen capped
  12. waitplaced into a CEM Microwave for 10 minutes at 80° C., while 60 watts of energy
  13. temperaturewas supplied via Powermax® (Simultaneous heating while cooling technology)
  14. customThe progress of the de-sulfonylation/de-acylation reaction

Sources & evidence

ORD record
ord-54d2741a21d14cb9ac7164cccae8015d
Source dataset
uspto-grants-2011_04
Patent number
US07928140B2

Reaction notes

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