Cesium carbonate → tert-butyl 2-(4-(6-fluoro-1-(phenylsulfonyl)-1H-indol-3-yl)-1H-pyrazol-1-yl)ethylcarbamate

HRID 2274766Notes

Reaction equation

[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:20]3[CH:21]=[N:22][NH:23][CH:24]=3)=[CH:7][N:8]2[S:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)(=[O:13])=[O:12])=[CH:4][CH:3]=1.Br[CH2:26][CH2:27][NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:20]3[CH:24]=[N:23][N:22]([CH2:26][CH2:27][NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH:21]=3)=[CH:7][N:8]2[S:11]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)(=[O:12])=[O:13])=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 85 °C

Procedure

To a solution of 6-fluoro-1-(phenylsulfonyl)-3-(1H-pyrazol-4-yl)-1H-indole (Intermediate 5; 500 mg; 1.46 mmol) in DMF (30 mL) was added tert-butyl 2-bromoethylcarbamate (658 mg; 2.94 mmol) and Cs2CO3 (1.43 g; 4.39 mmol) and catalytic amount of tetrabutylammonium iodide (107 mg; 0.29 mmol) under nitrogen. The reaction mixture was stirred at 85° C. for 24 hours. Most of DMF was removed and the residue was diluted with EtOAc (100 mL), washed with water (50 ml×3), brine (50 mL), dried over anhydrous Na2SO4, filtered, concentrated, and purified by reversed phase flash chromatography to afford 500 mg (70%) of the title compound as a yellow solid.

Workup

customMost of DMF was removed
additionthe residue was diluted with EtOAc (100 mL)
washwashed with water (50 ml×3), brine (50 mL)
dry with materialdried over anhydrous Na2SO4
filtrationfiltered
concentrationconcentrated
custompurified by reversed phase flash chromatography

Sources & evidence

ORD record: ord-533b33194b17476fadb7024e58e0c63d
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09126984B2

Reaction notes

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