Dichloromethane → 6-fluoro-3-(1-methyl-1H-pyrazol-4-yl)-1-(phenylsulfonyl)-1H-indole

HRID 2274760Notes

Reaction equation

Br[C:2]1[C:10]2[C:5](=[CH:6][C:7]([F:11])=[CH:8][CH:9]=2)[N:4]([S:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)(=[O:14])=[O:13])[CH:3]=1.[CH3:21][N:22]1[CH:26]=[C:25](B2OC(C)(C)C(C)(C)O2)[CH:24]=[N:23]1.CC([O-])=O.[K+].C(Cl)Cl>CN(C=O)C.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]>[F:11][C:7]1[CH:6]=[C:5]2[C:10]([C:2]([C:25]3[CH:24]=[N:23][N:22]([CH3:21])[CH:26]=3)=[CH:3][N:4]2[S:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)(=[O:14])=[O:13])=[CH:9][CH:8]=1

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of 3-bromo-6-fluoro-1-(phenylsulfonyl)-1H-indole (Intermediate 2; 1.0 g; 2.8 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (1.7 g; 8.4 mmol), KOAc (1.4 g; 14.0 mmol) and Pd(dppf)Cl2.CH2Cl2 (0.15 g; 0.18 mmol) in DMF (25 mL) flushed with nitrogen was heated to 90° C. overnight. The mixture was filtered through Celite, diluted with EtOAc (10 mL) and water (10 mL). The aqueous layer was extracted with EtOAc (20 mL×3). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, concentrated, and purified by a silica gel chromatography (petroleum ether/EtOAc=1/1) to afford 0.20 g (23%) of the title compound as a yellow solid.

Workup

filtrationThe mixture was filtered through Celite
additiondiluted with EtOAc (10 mL) and water (10 mL)
extractionThe aqueous layer was extracted with EtOAc (20 mL×3)
washThe combined organic layers were washed with brine
dry with materialdried over anhydrous Na2SO4
filtrationfiltered
concentrationconcentrated
custompurified by a silica gel chromatography (petroleum ether/EtOAc=1/1)

Sources & evidence

ORD record: ord-73c495d7db6f4de697b33bda1c0e82e8
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09126984B2

Reaction notes

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