Sodium Carbonate → 3-cyano-4-[2-(1H-pyrazol-5-yl)-4-(trifluoromethoxy)phenoxy]-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide

HRID 46243

반응식

HRID 46243 반응식
[C:1]([C:3]1[CH:4]=[C:5]([S:22]([NH:25][C:26]2[S:30][N:29]=[CH:28][N:27]=2)(=[O:24])=[O:23])[CH:6]=[CH:7][C:8]=1[O:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][C:11]=1I)#[N:2].C(OC[N:35]1[C:39](B2OC(C)(C)C(C)(C)O2)=[CH:38][CH:37]=[N:36]1)C.C(=O)([O-])[O-].[Na+].[Na+].ClCCl.CO.C(O)(=O)C>O.O1CCOCC1.Cl>[C:1]([C:3]1[CH:4]=[C:5]([S:22]([NH:25][C:26]2[S:30][N:29]=[CH:28][N:27]=2)(=[O:24])=[O:23])[CH:6]=[CH:7][C:8]=1[O:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][C:11]=1[C:37]1[NH:36][N:35]=[CH:39][CH:38]=1)#[N:2]

참가 물질

8

반응물 4

HCID 10340Sodium CarbonateHCID 21877243DCM MeOH AcOHHCID 594365983-cyano-N-(1,2,4-thiadiazol-5-yl)-4-[2-iodo-4-(trifluoromethoxy)phenoxy]benzenesulfonamideHCID 594366031-(ethoxymethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole2회

생성물 1

HCID 468409513-cyano-4-[2-(1H-pyrazol-5-yl)-4-(trifluoromethoxy)phenoxy]-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide수율 46.9%

시약·촉매·용매 3

HCID 313Hydrochloric Acid용매HCID 962Water용매HCID 312751,4-Dioxane용매2회

반응 조건

온도
85 °C

실험 절차

3-cyano-N-(1,2,4-thiadiazol-5-yl)-4-[2-iodo-4-(trifluoromethoxy)phenoxy]benzenesulfonamide (Preparation 760, 500 mg, 0.88 mmol), 1-(ethoxymethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (Preparation 337, 600 mg, 1.4 mmol), palladium (0) tetrakis triphenylphosphine (78 mg, 0.067 mmol) and sodium carbonate (420 mg, 3.963 mmol) were dissolved in a mixture of water (4 mL) and 1,4-dioxane (12 mL) and heated to 85° C. under N2 for 7 hours. Further 1-(ethoxymethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (100 mg 0.23 mmol) and palladium (0) tetrakis triphenylphosphine (10 mg, 0.008 mmol) were added and the reaction stirred at 85° C. under N2 for 18 hours. The reaction was quenched by the addition of ethyl acetate (20 mL) and saturated aqueous brine solution (20 mL). The organic layer was collected, dried over sodium sulphate and concentrated in vacuo before purification using silica gel column chromatography (v/v/v dichloromethane:methanol:acetic acid v/v/v 100:0:0 to 95:5:0.5) to afford a white solid. This was dissolved in 4M HCl in 1,4-dioxane (5 mL) and stirred at room temperature for 4 hours before concentration in vacuo and purification using silica gel column chromatography (v/v/v dichloromethane:methanol:acetic acid 100:0:0 to 90:10:1 to afford a residue that was triturated in dichloromethane (5 mL) to afford 210 mg of the title compound as a white solid as the HCl salt.

후처리

  1. customThe reaction was quenched by the addition of ethyl acetate (20 mL) and saturated aqueous brine solution (20 mL)
  2. customThe organic layer was collected
  3. dry with materialdried over sodium sulphate
  4. concentrationconcentrated in vacuo before purification
  5. customto afford a white solid
  6. stirringstirred at room temperature for 4 hours before concentration in vacuo and purification
  7. customto afford a residue that
  8. customwas triturated in dichloromethane (5 mL)

출처 및 근거

ORD 기록
ord-66ae178b66f447ec9b0973a525fc3e92
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08541588B2

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