Potassium Phosphate, Tribasic → 2-(3-(6-isopropoxypyridin-2-yl)-1-tosyl-1H-indol-5-yl)-5-(methylsulfonyl)-1,3,4-thiadiazole

HRID 634175Notes

Reaction equation

HRID 634175 reaction equation
I[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[S:12][C:13]([S:16]([CH3:19])(=[O:18])=[O:17])=[N:14][N:15]=3)[CH:9]=2)[N:4]([S:20]([C:23]2[CH:29]=[CH:28][C:26]([CH3:27])=[CH:25][CH:24]=2)(=[O:22])=[O:21])[CH:3]=1.[CH:30]([O:33][C:34]1[CH:39]=[CH:38][CH:37]=[C:36](B2OC(C)(C)C(C)(C)O2)[N:35]=1)([CH3:32])[CH3:31].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CC(O)C.O>[CH:30]([O:33][C:34]1[N:35]=[C:36]([C:2]2[C:10]3[C:5](=[CH:6][CH:7]=[C:8]([C:11]4[S:12][C:13]([S:16]([CH3:19])(=[O:17])=[O:18])=[N:14][N:15]=4)[CH:9]=3)[N:4]([S:20]([C:23]3[CH:24]=[CH:25][C:26]([CH3:27])=[CH:28][CH:29]=3)(=[O:21])=[O:22])[CH:3]=2)[CH:37]=[CH:38][CH:39]=1)([CH3:32])[CH3:31]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 426146482-Isopropoxy-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 683282122-(3-iodo-1-tosyl-1H-indol-5-yl)-5-(methylsulfonyl)-1,3,4-thiadiazole

Product 1

HCID 683282892-(3-(6-isopropoxypyridin-2-yl)-1-tosyl-1H-indol-5-yl)-5-(methylsulfonyl)-1,3,4-thiadiazoleYield 29.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
100 °C

Procedure

A yellow suspension of 2-(3-iodo-1-tosyl-1H-indol-5-yl)-5-(methylsulfonyl)-1,3,4-thiadiazole (300 mg, 0.536 mmol), 2-isopropoxy-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (CombiPhos Catalysts, Inc., Princeton, N.J.; 198 mg, 0.751 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)-dichloropalladium(II) (Aldrich; 18.99 mg, 0.027 mmol), and potassium phosphate (341 mg, 1.609 mmol) in a mixture of IPA (3.5 mL) and H2O (1.50 mL) was stirred at 100° C. for 10 min. The mixture was partitioned between EtOAc (80 mL) and H2O (50 mL) and the organic layer was separated. The aqueous layer was extracted with EtOAc (2×50 mL), and the combined organic extracts were dried over sodium sulfate, filtered, and concentrated onto silica gel. Chromatographic purification (silica gel, 0-60% EtOAc/Hex) furnished 2-(3-(6-isopropoxypyridin-2-yl)-1-tosyl-1H-indol-5-yl)-5-(methylsulfonyl)-1,3,4-thiadiazole (89.3 mg, 0.157 mmol, 29%) as a colorless oil. MS (ESI, pos. ion) m/z: 569.1 (M+1).

Workup

  1. customThe mixture was partitioned between EtOAc (80 mL) and H2O (50 mL)
  2. customthe organic layer was separated
  3. extractionThe aqueous layer was extracted with EtOAc (2×50 mL)
  4. dry with materialthe combined organic extracts were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated onto silica gel
  7. customChromatographic purification (silica gel, 0-60% EtOAc/Hex)

Sources & evidence

ORD record
ord-5e3124939c4149c8aa636e9b48036e4e
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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