Dimethyl Sulfone → 1-[1-(3-amino-3-methyl-butyl)-1H-indol-5-yl]-2-methanesulphonyl-ethanone

HRID 2355244Notes

Reaction equation

CC(C)([O-])C.[K+].[CH3:7][S:8]([CH3:11])(=[O:10])=[O:9].[NH2:12][C:13]([CH3:30])([CH3:29])[CH2:14][CH2:15][N:16]1[C:24]2[C:19](=[CH:20][C:21]([C:25](OC)=[O:26])=[CH:22][CH:23]=2)[CH:18]=[CH:17]1.C(O)(C(F)(F)F)=O>CS(C)=O>[NH2:12][C:13]([CH3:30])([CH3:29])[CH2:14][CH2:15][N:16]1[C:24]2[C:19](=[CH:20][C:21]([C:25](=[O:26])[CH2:7][S:8]([CH3:11])(=[O:10])=[O:9])=[CH:22][CH:23]=2)[CH:18]=[CH:17]1

Participants

Conditions

Temperature: 70 °C

Procedure

Potassium tert. butoxide (741 mg, 6.62 mmol) is added in two batches to a solution of dimethylsulphone (661 mg, 7.03 mmol) in 5 ml DMSO. After 10 minutes stirring at RT a solution of methyl 1-(3-amino-3-methyl-butyl)-indole-5-carboxylate (Component IV) (520 mg, 2.00 mmol) in 2 ml DMSO is added dropwise over 10 minutes. The reaction mixture is stirred for 16 hours at 70° C., acidified with TFA while cooling with ice and chromatographed on Microsorb C18-reverse-phase [acetonitrile (0.1% TFA)/water (0.13% TFA)=10:90→100:0]. Then the residue is chromatographed again on silica gel (DCM/methanol/ammonia=90:9:1).

Workup

additionis added dropwise over 10 minutes
temperaturewhile cooling with ice
customchromatographed on Microsorb C18-reverse-phase [acetonitrile (0.1% TFA)/water (0.13% TFA)=10:90→100:0]
customThen the residue is chromatographed again on silica gel (DCM/methanol/ammonia=90:9:1)

Sources & evidence

ORD record: ord-ac0047c543f243908115cd041dabe2dc
Source dataset: uspto-grants-2010_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07754756B2

Reaction notes

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