Potassium Carbonate → 2-(1H-indol-5-yl)-5-(methylthio)-1,3,4-thiadiazole

HRID 634120Notes

Reaction equation

HRID 634120 reaction equation
Br[C:2]1[S:3][C:4]([S:7][CH3:8])=[N:5][N:6]=1.CC1(C)C(C)(C)OB([C:17]2[CH:18]=[C:19]3[C:23](=[CH:24][CH:25]=2)[NH:22][CH:21]=[CH:20]3)O1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.CCOC(C)=O.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>[NH:22]1[C:23]2[C:19](=[CH:18][C:17]([C:2]3[S:3][C:4]([S:7][CH3:8])=[N:5][N:6]=3)=[CH:25][CH:24]=2)[CH:20]=[CH:21]1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 27347725-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indoleHCID 222696212-Bromo-5-(methylsulfanyl)-1,3,4-thiadiazole

Product 1

HCID 683282152-(1H-indol-5-yl)-5-(methylthio)-1,3,4-thiadiazoleYield 50%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 2-bromo-5-(methylthio)-1,3,4-thiadiazole (18.5 g, 87 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (21 g, 86 mmol) in p-dioxane (5 mL)/H2O (5 mL) was added Pd(PPh3)4 (15.1 g, 13 mmol) followed by K2CO3 (48.2 g, 349 mmol). The reaction was heated under argon atmosphere at 110° C. for 4 h, then cooled to RT. The mixture was diluted with EtOAc and H2O, and the two layers were separated. The aqueous layer was extracted with EtOAc. The combined organic layers were dried, filtered and concentrated. The crude material was recrystallized in EtOH to give 2-(1H-indol-5-yl)-5-(methylthio)-1,3,4-thiadiazole (10 g, 50%) as an off-white solid. MS (ESI, pos. ion) m/z: 247.8 (M+1). 1H-NMR (DMSO-d6, 300 MHz): 2.8 (s, 3H), 6.6 (d, 1H), 7.5 (t, 1H), 7.55 (dd, 1H), 8.1 (s, 1H), 11.5 (s, 1H).

Workup

  1. temperaturecooled to RT
  2. customthe two layers were separated
  3. extractionThe aqueous layer was extracted with EtOAc
  4. customThe combined organic layers were dried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was recrystallized in EtOH

Sources & evidence

ORD record
ord-e41997a3bcc543d5a53ef151cbc14e52
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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