Potassium Carbonate → 3-(1,1-Dioxidotetrahydro-3-thienyl)-5-[5-(hexahydro-1H-azepin-1-ylmethyl)-3-thienyl]-1H-indole-7-carboxamide

HRID 656122Notes

Reaction equation

HRID 656122 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[CH2:18][CH2:17][S:16](=[O:20])(=[O:19])[CH2:15]1.CC1(C)C(C)(C)OB([C:29]2[CH:30]=[C:31]([CH2:34][N:35]3[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]3)[S:32][CH:33]=2)O1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[O:19]=[S:16]1(=[O:20])[CH2:17][CH2:18][CH:14]([C:5]2[C:4]3[C:8](=[C:9]([C:11]([NH2:13])=[O:12])[CH:10]=[C:2]([C:29]4[CH:30]=[C:31]([CH2:34][N:35]5[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41]5)[S:32][CH:33]=4)[CH:3]=3)[NH:7][CH:6]=2)[CH2:15]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 593325635-bromo-3-(1,1-dioxidotetrahydro-3-thienyl)-1H-indole-7-carboxamideHCID 593327881-{[4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-2-thienyl]methyl}hexahydro-1H-azepine

Product 1

HCID 250722263-(1,1-Dioxidotetrahydro-3-thienyl)-5-[5-(hexahydro-1H-azepin-1-ylmethyl)-3-thienyl]-1H-indole-7-carboxamideYield 28.4%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

5-bromo-3-(1,1-dioxidotetrahydro-3-thienyl)-1H-indole-7-carboxamide (0.040 g, 0.112 mmol) and 1-{[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-thienyl]methyl}hexahydro-1H-azepine (0.055 g, 0.172 mmol) was dissolved in a 6:1 solution of 1,4 dioxane/water in a 20 mL microwave reaction vessel. Potassium carbonate (0.077 g, 0.560 mmol) was added and the solution was degassed with Argon. PdCl2(dppf) (0.014 g, 0.019 mmol) was added and the reaction was heated in a microwave at 100° C. for 20 min. The solution was passed through a StratoSphere SPE PL-Thiol MP SPE column to remove palladium and purified on Gilson preparative HPLC using Acetonitrile/Water with 0.1% TFA. The desired fractions were concentrated, giving 0.015 g (28%) of the title compound.

Workup

  1. customthe solution was degassed with Argon
  2. customto remove palladium
  3. custompurified on Gilson preparative HPLC
  4. concentrationThe desired fractions were concentrated

Sources & evidence

ORD record
ord-7395e17cbc594965af1144121c677a2f
Source dataset
uspto-grants-2011_12
Patent number
US08071584B2

Reaction notes

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