Triethylamine → 5-bromo-3-[1-(ethanesulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide

HRID 562015Notes

Reaction equation

[CH2:1]([S:3](Cl)(=[O:5])=[O:4])[CH3:2].Cl.[Br:8][C:9]1[CH:10]=[C:11]2[C:15](=[C:16]([C:18]([NH2:20])=[O:19])[CH:17]=1)[NH:14][CH:13]=[C:12]2[CH:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1.C(N(CC)CC)C.CCOC(C)=O.O>CN(C=O)C>[Br:8][C:9]1[CH:10]=[C:11]2[C:15](=[C:16]([C:18]([NH2:20])=[O:19])[CH:17]=1)[NH:14][CH:13]=[C:12]2[CH:21]1[CH2:26][CH2:25][N:24]([S:3]([CH2:1][CH3:2])(=[O:5])=[O:4])[CH2:23][CH2:22]1

Participants

Conditions

Temperature: 0 °C

Procedure

Ethanesulfonyl chloride (4.5 mL, 47.4 mmol) was added dropwise to a solution of 5-bromo-3-(4-piperidinyl)-1H-indole-7-carboxamide hydrochloride (8.49 g, 23.7 mmol) and triethylamine (13.2 mL, 94.7 mmol) in DMF (80 mL) at 0° C. (bath temperature). The reaction mixture was stirred at 0° C. for 45 min. and was then poured into a 2:1 mixture of EtOAc/H2O (300 mL). The resulting precipitate was filtered off, washed with EtOAc (2×50 mL), and set aside. The EtOAc/H2O bilayer was separated, and the aqueous layer was extracted with EtOAc (2×100 mL). The combined organic layers were washed with saturated NaCl (1×100 mL), dried (MgSO4), filtered, and concentrated under reduced pressure. The crude product was combined with the precipitate isolated above and washed with MeOH (1×10 mL) to give 8.19 g of the title compound (83%).

Workup

filtrationThe resulting precipitate was filtered off
washwashed with EtOAc (2×50 mL)
customThe EtOAc/H2O bilayer was separated
extractionthe aqueous layer was extracted with EtOAc (2×100 mL)
washThe combined organic layers were washed with saturated NaCl (1×100 mL)
dry with materialdried (MgSO4)
filtrationfiltered
concentrationconcentrated under reduced pressure
customisolated above and
washwashed with MeOH (1×10 mL)

Sources & evidence

ORD record: ord-997044f5a55e4d0997426b21cf651a2a
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08063071B2

Reaction notes

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