Potassium Carbonate → 5-[5-(1-Azetidinylmethyl)-3-thienyl]-3-(1,1-dioxidotetrahydro-3-thienyl)-1H-indole-7-carboxamide

HRID 656121Notes

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[CH2:38][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]>[N:35]1([CH2:34][C:31]2[S:32][CH:33]=[C:29]([C:2]3[CH:3]=[C:4]4[C:8](=[C:9]([C:11]([NH2:13])=[O:12])[CH:10]=3)[NH:7][CH:6]=[C:5]4[CH:14]3[CH2:18][CH2:17][S:16](=[O:20])(=[O:19])[CH2:15]3)[CH:30]=2)[CH2:38][CH2:37][CH2:36]1

Participants

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}azetidine (0.035 g, 0.126 mmol, 1.1 eq) 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, 5 eq) 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. 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 0.011 g (23%) of the title compound.

Workup

customthe solution was degassed with Argon
customto remove palladium
custompurified on Gilson preparative HPLC
concentrationThe desired fractions were concentrated

Sources & evidence

ORD record: ord-d443c18e4e47419ca6d2618ccf948d6e
Source dataset: uspto-grants-2011_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08071584B2

Reaction notes

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