Ethyl Acetate → methyl 6-chloro-5-{4-[2-(piperazin-1-yl)ethoxy]phenyl}-1H-indole-3-carboxylate

HRID 1054681

Reaction equation

[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([O:13][CH3:14])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1B1OCC(C)(C)CO1.Br[C:24]1[CH:38]=[CH:37][C:27]([O:28][CH2:29][CH2:30][N:31]2[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]2)=[CH:26][CH:25]=1.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>C1(C)C=CC=CC=1.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]>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([O:13][CH3:14])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:24]1[CH:38]=[CH:37][C:27]([O:28][CH2:29][CH2:30][N:31]2[CH2:32][CH2:33][NH:34][CH2:35][CH2:36]2)=[CH:26][CH:25]=1

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of methyl 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylate (80 mg, 0.15 mmol), 1-(2-(4-bromophenoxy)ethyl)piperazine (86 mg, 0.30 mmol), 2.0 M aqueous potassium carbonate (0.50 mL, 1.0 mmol), and Pd(dppf)Cl2 (10 mg, 0.01 mmol) in toluene/ethanol (1.44 mL/0.48 mL) was stirred at 110° C. for 2.5 hours. The mixture was poured into ethyl acetate and washed with water. The organic phase was dried over sodium sulfate, filtered, and concentrated in vacuo to give a residue, which was purified by preparative TLC to give the title compound (40 mg, 40% yield) as a white solid. 1H NMR (400 MHz, CDCl3): δ8.50 (s, 1 H), 8.10 (s, 1 H), 7.98 (s, 1 H), 7.55 (m, 1 H), 7.45 (m, 2 H), 7.00 (m, 2 H), 4.20 (m, 2 H), 3.90 (s, 3 H), 2.99 (m, 4 H), 2.85 (m, 2 H), 2.60 (m, 4 H).

Workup

washwashed with water
dry with materialThe organic phase was dried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customto give a residue, which
customwas purified by preparative TLC

Sources & evidence

ORD record: ord-3f60ca154ce5409697c81f8cb072bd13
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394285B2

Linked notes

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