Potassium Carbonate → 3-(1,1-Dioxidotetrahydro-2H-thiopyran-4-yl)-5-(1H-indazol-5-yl)-1H-indole-7-carboxamide

HRID 656099Notes

Reaction equation

[O:1]=[S:2]1(=[O:29])[CH2:7][CH2:6][CH:5]([C:8]2[C:16]3[C:11](=[C:12]([C:26]([NH2:28])=[O:27])[CH:13]=[C:14](B4OC(C)(C)C(C)(C)O4)[CH:15]=3)[NH:10][CH:9]=2)[CH2:4][CH2:3]1.Br[C:31]1[CH:32]=[C:33]2[C:37](=[CH:38][CH:39]=1)[NH:36][N:35]=[CH:34]2.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:29]=[S:2]1(=[O:1])[CH2:7][CH2:6][CH:5]([C:8]2[C:16]3[C:11](=[C:12]([C:26]([NH2:28])=[O:27])[CH:13]=[C:14]([C:31]4[CH:32]=[C:33]5[C:37](=[CH:38][CH:39]=4)[NH:36][N:35]=[CH:34]5)[CH:15]=3)[NH:10][CH:9]=2)[CH2:4][CH2:3]1

Participants

Conditions

Temperature: 100 °C

Procedure

3-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-7-carboxamide (0.085 g, 0.203 mmol) and 5-bromo-1H-indazole (0.048 g, 0.244 mmol, 1.2 eq) was dissolved in a 6:1 solution of 1,4 dioxane/water in a 20 mL microwave reaction vessel. Potassium carbonate (0.128, 0.929 mmol, 4.6 eq) was added and the solution was degassed with Argon. PdCl2(dppf) (0.023 g, 0.032 mmol, 0.16 eq) 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. 0.020 g (24%) product obtained.

Workup

customthe solution was degassed with Argon
customto remove palladium
custompurified on Gilson preparative HPLC

Sources & evidence

ORD record: ord-8fb03fba4d5144b0ae237b7011a80268
Source dataset: uspto-grants-2011_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08071584B2

Reaction notes

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