Potassium Carbonate → tert-butyl 4-((4-(N-(2-hydroxyethyl)-N-methylcarbamoyl)phenyl)(quinolin-8-yl)methylene)piperidine-1-carboxylate

HRID 1011281Notes

Reaction equation

HRID 1011281 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=[C:14](Br)[C:15]2[CH:20]=[CH:19][C:18]([C:21](=[O:27])[N:22]([CH2:24][CH2:25][OH:26])[CH3:23])=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N:29]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][C:37]=2B(O)O)[CH:32]=[CH:31][CH:30]=1.C([O-])([O-])=O.[K+].[K+]>CC(O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=[C:14]([C:15]2[CH:20]=[CH:19][C:18]([C:21](=[O:27])[N:22]([CH2:24][CH2:25][OH:26])[CH3:23])=[CH:17][CH:16]=2)[C:37]2[CH:36]=[CH:35][CH:34]=[C:33]3[C:38]=2[N:29]=[CH:30][CH:31]=[CH:32]3)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27343808-Quinolineboronic acidHCID 24897463tert-butyl 4-((4-(N-(2-hydroxyethyl)-N-methylcarbamoyl)phenyl)bromomethylene)piperidine-1-carboxylate

Product 1

HCID 24897464tert-butyl 4-((4-(N-(2-hydroxyethyl)-N-methylcarbamoyl)phenyl)(quinolin-8-yl)methylene)piperidine-1-carboxylateYield 108.6%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

Compound 1A (4.0 g, 8.8 mmol), 8-quinolineboronic acid (3.0 g, 17 6 mmol), POPd (0.088 g, 0.18 mmol), and K2CO3 (3.6 g, 26 4 mmol) in iPrOH (90 mL) were stirred in a preheated 100° C. oil bath under nitrogen for 20 h. The reaction was filtered through celite and concentrated. The material was purified by chromatography on silica gel (gradient 2-5% MeOH in CH2Cl2) to give a yellow solid 1B (3.27 g, 74%). 1H NMR (500.333 MHz, CDCl3) δ 8.91 (dd, J=4.0, 1.6 Hz, 1H), 8.13 (dd, J=8.2, 1.5 Hz, 1H), 7.74 (dt, J=9.5, 3.5 Hz, 1H), 7.50 (d, J=2.5 Hz, 2H), 7.37-7.33 (m, 5H), 3.86 (br s, 2H), 3.68 (br s, 2H), 3.59 (br s, 2H), 3.52-3.43 (m, 3H), 3.34-3.23 (m, 2H), 3.03 (s, 3H), 2.57-2.52 (m, 2H), 2.01 (dd, J=19.3, 7.6 Hz, 2H), 1.44 (s, 9H). MS ES+ 502.2.

Workup

  1. filtrationThe reaction was filtered through celite
  2. concentrationconcentrated
  3. customThe material was purified by chromatography on silica gel (gradient 2-5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-e216a8c3732d46048739e1601e84af71
Source dataset
uspto-grants-2011_07
Patent number
US07977355B2

Reaction notes

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