Hydrochloric Acid → 5-(4-Chloro-2-(1H-pyrazol-4-YL)phenyl)-N-(1,2,4-thiadiazol-5-YL)naphthalene-2 sulfonamide

HRID 1473293Notes

Reaction equation

HRID 1473293 reaction equation
Br[C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:18]=[CH:17][CH:16]=[C:15]2[C:10]=1[CH:11]=[CH:12][C:13]([S:19]([N:22](CC1C=CC(OC)=CC=1OC)[C:23]1[S:27][N:26]=[CH:25][N:24]=1)(=[O:21])=[O:20])=[CH:14]2.C(=O)([O-])[O-].[K+].[K+].CC1(C)C(C)(C)OB([C:53]2[CH:54]=[N:55][N:56](C(OC(C)(C)C)=O)[CH:57]=2)O1.Cl.C(Cl)Cl.C(O)(C(F)(F)F)=O>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.O1CCOCC1>[Cl:8][C:6]1[CH:5]=[CH:4][C:3]([C:9]2[CH:18]=[CH:17][CH:16]=[C:15]3[C:10]=2[CH:11]=[CH:12][C:13]([S:19]([NH:22][C:23]2[S:27][N:26]=[CH:25][N:24]=2)(=[O:20])=[O:21])=[CH:14]3)=[C:2]([C:53]2[CH:54]=[N:55][NH:56][CH:57]=2)[CH:7]=1

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 16217654tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylateHCID 866873475-(2-Bromo-4-chlorophenyl)-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-YL)naphthalene-2-sulfonamide

Product 1

HCID 896145085-(4-Chloro-2-(1H-pyrazol-4-YL)phenyl)-N-(1,2,4-thiadiazol-5-YL)naphthalene-2 sulfonamide

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A pressure vessel was charged with 5-(2-bromo-4-chlorophenyl)-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide (0.8 g, 1.268 mmol), potassium carbonate (1.227 g, 8.88 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (0.748 g, 2.54 mmol), tetrakis(triphenylphosphine)palladium(0) (0.147 g, 0.127 mmol), dioxane (8.45 mL) and water (4.23 mL). The reaction was heated in a microwave at 100° C. for 30 min. The reaction mixture was cooled to room temperature and 2N HCl (10 mL) was then added dropwise to neutralize the base. The aqueous layer was then washed with DCM (three times). The organic layers were combined and dried over sodium sulfate, filtered over a layer of diatomaceous Earth® (diatomaceous earth) and concentrated under a vacuum to provide a yellow oil. To this oil was added DCM (12.68 mL, 1.268 mmol) and TFA (0.488 mL, 6.34 mmol). The resulting mixture was stirred for 1 h at rt. LC/MS indicated that the dimethoxybenzyl (DMB)-protected intermediate remained. The mixture was then heated to 50° C. for 1 h. LC/MS indicated that the desired product (M+H=467.8) was generated. The mixture was concentrated, diluted with DCM (3 mL) and purified by reverse phase HPLC using a Phenomenex Gemini 5 μm, C18, 110 Å, 150×30 mm column eluting with a mixture of 0.1% TFA in acetonitrile/water. The fractions containing product were dried to provide a white solid. 5-(4-chloro-2-(1H-pyrazol-4-yl)phenyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide (0.165 g, 0.352 mmol). 1H NMR (500 MHz, DMSO-d6) δ ppm 2.08 (s, 2H) 2.54 (s, 1H) 7.02 (br. s., 2H) 7.30 (d, J=8.23 Hz, 1H) 7.40-7.47 (m, 2H) 7.56 (d, J=7.05 Hz, 1H) 7.65 (dd, J=8.87, 1.92 Hz, 1H) 7.69-7.76 (m, 1H) 7.79 (d, J=2.14 Hz, 1H) 8.26 (d, J=8.23 Hz, 1H) 8.44 (s, 1H) 8.53 (d, J=1.71 Hz, 1H); m/z (ESI) 467.8 (M+H)+.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washThe aqueous layer was then washed with DCM (three times)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered over a layer of diatomaceous Earth® (diatomaceous earth)
  5. concentrationconcentrated under a vacuum
  6. customto provide a yellow oil
  7. temperatureThe mixture was then heated to 50° C. for 1 h

Sources & evidence

ORD record
ord-5e46f7f8d01645d3a14cd4cf36c7716c
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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