Water → 3-(1,1-Dioxidotetrahydro-2H-thiopyran-4-yl)-5-(5-{3-methyl-3-[(triethylsilyl)oxy]butyl}-2-thienyl)-1H-indole-7-carboxamide

HRID 387319Notes

Reaction equation

HRID 387319 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:11]([NH2:13])=[O:12])[CH:10]=1)[NH:7][CH:6]=[C:5]2[CH:14]1[CH2:19][CH2:18][S:17](=[O:21])(=[O:20])[CH2:16][CH2:15]1.[CH3:22][C:23]([O:41][Si:42]([CH2:47][CH3:48])([CH2:45][CH3:46])[CH2:43][CH3:44])([CH3:40])[CH2:24][CH2:25][C:26]1[S:27][C:28](B2OC(C)(C)C(C)(C)O2)=[CH:29][CH:30]=1.C(=O)([O-])[O-].[K+].[K+].O>O1CCOCC1>[O:20]=[S:17]1(=[O:21])[CH2:18][CH2:19][CH:14]([C:5]2[C:4]3[C:8](=[C:9]([C:11]([NH2:13])=[O:12])[CH:10]=[C:2]([C:28]4[S:27][C:26]([CH2:25][CH2:24][C:23]([CH3:40])([O:41][Si:42]([CH2:47][CH3:48])([CH2:43][CH3:44])[CH2:45][CH3:46])[CH3:22])=[CH:30][CH:29]=4)[CH:3]=3)[NH:7][CH:6]=2)[CH2:15][CH2:16]1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 593327575-Bromo-3-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1H-indole-7-carboxamideHCID 66746892({1,1-Dimethyl-3-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-thienyl]propyl}oxy)(triethyl)silane

Product 1

HCID 593327423-(1,1-Dioxidotetrahydro-2H-thiopyran-4-yl)-5-(5-{3-methyl-3-[(triethylsilyl)oxy]butyl}-2-thienyl)-1H-indole-7-carboxamide

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

5-bromo-3-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1H-indole-7-carboxamide (90 mg, 0.24 mmol), ({1,1-dimethyl-3-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-thienyl]propyl}oxy)(triethyl)silane (149 mg, 0.36 mmol, 1.5 eq), potassium carbonate (200 mg, 1.4 mmol, 6 eq), and palladium tetrakistriphenylphosphine (28 mg, 0.024 mmol, 0.1 eq) were diluted in dioxane (1.5 mL) and water (0.5 mL) in a 2-5 mL microwave vial. The mixture was degassed by bubbling argon through for 5 minutes, then heated in a microwave oven at 150° C. under high absorption for 40 minutes. The mixture was filtered through a thiol SPE cartridge, then concentrated to give the crude product as a brown oil. This material was purified by Isco Combiflash, 40 gram column, eluting with 0-15% methanol in dichloromethane. The desired product was obtained as a brownish tarry substance and was re-purified by ammonium hydroxide Gilson eluting with 20-95% acetonitrile in water. The product fractions were concentrated in a Genevac EZ2 evaporator to give the title compound as a light yellow solid (55 mg, 40%).

Workup

  1. customThe mixture was degassed
  2. customby bubbling argon through for 5 minutes
  3. filtrationThe mixture was filtered through a thiol SPE cartridge
  4. concentrationconcentrated
  5. customto give the crude product as a brown oil
  6. customThis material was purified by Isco Combiflash, 40 gram column
  7. washeluting with 0-15% methanol in dichloromethane

Sources & evidence

ORD record
ord-64b88f8e8ca54de99879e5bdd648f796
Source dataset
uspto-grants-2013_02
Patent number
US08372875B2

Reaction notes

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