Diethylamine → N-[(4-chlorophenyl)methyl]-1-methyl-6-(morpholinomethyl)-4-oxo-8-[2-(3-pyridyl)ethynyl]quinoline-3-carboxamide

HRID 1265005Notes

Reaction equation

HRID 1265005 reaction equation
[Cl:1][C:2]1[CH:31]=[CH:30][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:19](=[O:20])[C:18]3[C:13](=[C:14](I)[CH:15]=[C:16]([CH2:21][N:22]4[CH2:27][CH2:26][O:25][CH2:24][CH2:23]4)[CH:17]=3)[N:12]([CH3:29])[CH:11]=2)=[O:9])=[CH:4][CH:3]=1.[C:32]([C:34]1[CH:35]=[N:36][CH:37]=[CH:38][CH:39]=1)#[CH:33].C(NCC)C>[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CN(C)C=O>[Cl:1][C:2]1[CH:31]=[CH:30][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:19](=[O:20])[C:18]3[C:13](=[C:14]([C:33]#[C:32][C:34]4[CH:35]=[N:36][CH:37]=[CH:38][CH:39]=4)[CH:15]=[C:16]([CH2:21][N:22]4[CH2:27][CH2:26][O:25][CH2:24][CH2:23]4)[CH:17]=3)[N:12]([CH3:29])[CH:11]=2)=[O:9])=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 8021DiethylamineHCID 1860033-EthynylpyridineHCID 12095879N-(4-chlorobenzyl)-8-iodo-1-methyl-6-(4-morpholinylmethyl)-4-oxo-1,4-dihydro-3-quinolinecarboxamide

Product 1

HCID 5278421N-[(4-chlorophenyl)methyl]-1-methyl-6-(morpholinomethyl)-4-oxo-8-[2-(3-pyridyl)ethynyl]quinoline-3-carboxamideYield 86%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

A flame-dried flask under an atmosphere of nitrogen gas containing N-(4-chlorobenzyl)-8-iodo-1-methyl-6-(morpholin-4-ylmethyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide (Preparation # 15) (0.28 g) is treated with copper (I) iodide (0.01 g), dichlorobis(triphenylphosphine)palladium (II) (0.03 g) and 3-ethynylpyridine (0.10 g). The solids are treated with dimethylformamide (DMF) (3 mL) and diethylamine (3 mL). The resulting suspension is stirred for 2 days and is then concentrated under reduced pressure. The residue is flash column chromatographed on silica eluting with 2% to 4% methanol in dichloromethane. The product-containing fractions are combined and concentrated under reduced pressure. The resulting material is crystallized from methanol:acetonitrile to afford the title compound (0.23 g) as a tan solid.

Workup

  1. concentrationis then concentrated under reduced pressure
  2. customchromatographed on silica eluting with 2% to 4% methanol in dichloromethane
  3. concentrationconcentrated under reduced pressure
  4. customThe resulting material is crystallized from methanol

Sources & evidence

ORD record
ord-32c51034a3214ff88e2e2c48cf9ae361
Source dataset
uspto-grants-2003_04
Patent number
US06544990B2

Reaction notes

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