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

HRID 1265004Notes

Reaction equation

HRID 1265004 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(NCC)C.[C:37]([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][N:40]=1)#[CH:38]>[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:38]#[C:37][C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][N:40]=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 137268EthynylpyridineHCID 12095879N-(4-chlorobenzyl)-8-iodo-1-methyl-6-(4-morpholinylmethyl)-4-oxo-1,4-dihydro-3-quinolinecarboxamide

Product 1

HCID 5278420N-[(4-chlorophenyl)methyl]-1-methyl-6-(morpholinomethyl)-4-oxo-8-[2-(2-pyridyl)ethynyl]quinoline-3-carboxamide

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), dimethylformamide (DMF) (3 mL) and diethylamine (3 mL). The resulting stirring suspension is treated with 2-ethynylpyridine (0.1 mL). After stirring overnight, the suspension is concentrated under reduced pressure and then in vacuo. The residue is adsorbed onto silica gel and is flash column chromatographed on silica eluting with 2% to 6% methanol in dichloromethane. The product-containing fractions are combined and concentrated under reduced pressure. The resulting material is crystallized from a mixture of methanol:acetonitrile to afford the title compound (0.22 g) as a white solid.

Workup

  1. stirringAfter stirring overnight
  2. concentrationthe suspension is concentrated under reduced pressure
  3. customchromatographed on silica eluting with 2% to 6% methanol in dichloromethane
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting material is crystallized from a mixture of methanol

Sources & evidence

ORD record
ord-1133c62d5f324d80b2e7a166c0ab95a5
Source dataset
uspto-grants-2003_04
Patent number
US06544990B2

Reaction notes

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