Water → 5-(4-Chloro-2-(difluoromethoxy)phenyl)-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-YL)naphthalene-2-sulfonamide

HRID 1473290Notes

Reaction equation

HRID 1473290 reaction equation
[CH3:1][O:2][C:3]1[CH:37]=[C:36]([O:38][CH3:39])[CH:35]=[CH:34][C:4]=1[CH2:5][N:6]([C:29]1[S:33][N:32]=[CH:31][N:30]=1)[S:7]([C:10]1[CH:19]=[CH:18][C:17]2[C:12](=[CH:13][CH:14]=[CH:15][C:16]=2B2OC(C)(C)C(C)(C)O2)[CH:11]=1)(=[O:9])=[O:8].Br[C:41]1[CH:46]=[CH:45][C:44]([Cl:47])=[CH:43][C:42]=1[O:48][CH:49]([F:51])[F:50].C(=O)([O-])[O-].[Na+].[Na+].O>C(O)(C)(C)C.O1CCOCC1>[Cl:47][C:44]1[CH:45]=[CH:46][C:41]([C:16]2[CH:15]=[CH:14][CH:13]=[C:12]3[C:17]=2[CH:18]=[CH:19][C:10]([S:7]([N:6]([CH2:5][C:4]2[CH:34]=[CH:35][C:36]([O:38][CH3:39])=[CH:37][C:3]=2[O:2][CH3:1])[C:29]2[S:33][N:32]=[CH:31][N:30]=2)(=[O:9])=[O:8])=[CH:11]3)=[C:42]([O:48][CH:49]([F:50])[F:51])[CH:43]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 222953811-Bromo-4-chloro-2-(difluoromethoxy)benzene2×HCID 86687343N-(2,4-dimethoxybenzyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2 sulfonamide2×

Product 1

HCID 866873485-(4-Chloro-2-(difluoromethoxy)phenyl)-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-YL)naphthalene-2-sulfonamide

Reagents, catalysts & solvents 2

HCID 6386tert-ButanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A microwave vial was charged with N-(2,4-dimethoxybenzyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide (Intermediate E) (130 mg, 0.229 mmol), 1-bromo-4-chloro-2-(difluoromethoxy)benzene (Intermediate J) (118 mg, 0.458 mmol) and Pd(dppf)Cl2DCM (37.4 mg, 0.046 mmol). Dioxane (1145 μl) and t-butanol (1145 μl) were added to the reaction vial followed by sodium carbonate in water (362 μl, 0.687 mmol, 1.9 M). The vial was purged with nitrogen and sealed. The mixture was stirred and sonicated for 5 min. The resulting light red mixture was then heated in a microwave at 100° C. for 30 min LC/MS indicated complete conversion of boronic ester to the desired product. The reaction was cooled to rt and filtered through a fritted funnel with an aid of DCM (15 mL). The filtrate was acidified with 2N aqueous HCl to a pH of about 1. After stirring for 5 min at room temperature, the product was extracted with DCM (2×20 mL). The organic layers were combined, washed with brine, dried over MgSO4, filtered, and concentrated to afford a dark oil. MS (ESI): 639.8 [M+Na]+

Workup

  1. customThe vial was purged with nitrogen
  2. customsealed
  3. customsonicated for 5 min
  4. temperatureThe reaction was cooled to rt
  5. filtrationfiltered through a fritted funnel with an aid of DCM (15 mL)
  6. stirringAfter stirring for 5 min at room temperature
  7. extractionthe product was extracted with DCM (2×20 mL)
  8. washwashed with brine
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customto afford a dark oil

Sources & evidence

ORD record
ord-f7e4c819a6684a009b337e0b33c8ef31
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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