Potassium Carbonate → 3-[(1,1-Dioxidotetrahydro-3-thienyl)methyl]-5-phenyl-1H-indole-7-carboxamide

HRID 656160Notes

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[CH2:14][CH:15]1[CH2:19][CH2:18][S:17](=[O:21])(=[O:20])[CH2:16]1.[C:22]1(B(O)O)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.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:20]=[S:17]1(=[O:21])[CH2:18][CH2:19][CH:15]([CH2:14][C:5]2[C:4]3[C:8](=[C:9]([C:11]([NH2:13])=[O:12])[CH:10]=[C:2]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[CH:3]=3)[NH:7][CH:6]=2)[CH2:16]1

Participants

Conditions

Temperature: 120 °C

Procedure

5-bromo-3-[(1,1-dioxidotetrahydro-3-thienyl)methyl]-1H-indole-7-carboxamide (40 mg, 0.108 mmol), phenylboronic acid (19.71 mg, 0.162 mmol, 1.5 eq), PdCl2(dppf) (7.88 mg, 10.77 μmol, 0.1 eq), potassium carbonate (44.7 mg, 0.323 mmol, 3 eq) were diluted in a mixture of 1,4-dioxane (3 mL) and water (1 mL), in a 2-5 mL biotage microwave reaction tube. The mixture was degassed by bubbling nitrogen through for 5 minutes and was then heated in a microwave at high absorption for 15 minutes at 120° C. The reaction was filtered through a thiol SPE cartridge (polymer labs) and was concentrated and purified by Gilson HPLC with trifluoroacetic acid buffer. The desired product fractions were combined and concentrated in an EZ2 Genevac evaporator, giving 35.3 mg (84%) of the title compound.

Workup

customThe mixture was degassed
customby bubbling nitrogen through for 5 minutes
filtrationThe reaction was filtered through a thiol SPE cartridge (polymer labs)
concentrationwas concentrated
custompurified by Gilson HPLC with trifluoroacetic acid buffer
concentrationconcentrated in an EZ2 Genevac evaporator

Sources & evidence

ORD record: ord-99921f0db5b74f83957f2faa8af03df5
Source dataset: uspto-grants-2011_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08071584B2

Reaction notes

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