Dimethylformamide → (+/-)-2-Amino-1-cyclopentyl-7-(3,4-dihydroxy-3-methylbut-1-yn-1-yl)-N-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxamide

HRID 1260594Notes

Reaction equation

HRID 1260594 reaction equation
[NH2:1][C:2]1[N:3]([CH:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)[C:4]2[C:9]([C:10](=[O:16])[C:11]=1[C:12]([NH:14][CH3:15])=[O:13])=[CH:8][CH:7]=[C:6](Cl)[N:5]=2.[CH3:23][C:24]([OH:29])([C:27]#[CH:28])[CH2:25][OH:26].CN(C)C=O>[Cu]I.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.C(N(CC)CC)C>[NH2:1][C:2]1[N:3]([CH:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)[C:4]2[C:9]([C:10](=[O:16])[C:11]=1[C:12]([NH:14][CH3:15])=[O:13])=[CH:8][CH:7]=[C:6]([C:28]#[C:27][C:24]([OH:29])([CH3:23])[CH2:25][OH:26])[N:5]=2

Participants

7

Reactant 3

HCID 6228DimethylformamideHCID 221369052-Methylbut-3-yne-1,2-diolHCID 866423412-amino-7-chloro-1-cyclopentyl-N-methyl-4-oxo-1,4-dihydro[1,8]-naphthyridine-3-carboxamide

Product 1

HCID 67081701(+/-)-2-Amino-1-cyclopentyl-7-(3,4-dihydroxy-3-methylbut-1-yn-1-yl)-N-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxamideYield 97.4%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
100 °C

Procedure

15 g of 2-amino-7-chloro-1-cyclopentyl-N-methyl-4-oxo-1,4-dihydro[1,8]-naphthyridine-3-carboxamide (53.44 mmol) and 11.11 g of (±)-2-methylbut-3-yne-1,2-diol (83.39 mmol) are introduced successively into a mixture of 267 ml of dimethylformamide and 104 ml of triethylamine in a 500 ml three-necked flask. The reaction mixture is sparged with argon for 15 minutes and then 1.02 g of CuI (5.34 mmol) and 1.87 g of bis(triphenylphosphine) palladium(II)dichloride (2.67 mmol) are successively added. The reaction mixture is heated for 30 minutes at 100° C. and then concentrated under reduced vacuum. The residue is taken up in a chloroform/water mixture and the insoluble material is filtered off. 20 g of a solid are obtained, which is purified by silica chromatography (solid deposit after solubilization in a tetrahydrofuran/methanol mixture and then elution with a dichloromethane/methanol gradient, 99:1 to 80:20) so as to give 7.5 g of expected product in the form of a beige solid.

Workup

  1. customThe reaction mixture is sparged with argon for 15 minutes
  2. concentrationconcentrated under reduced vacuum
  3. filtrationthe insoluble material is filtered off

Sources & evidence

ORD record
ord-56da1413c3a24a36b045cbb43fe08cb9
Source dataset
uspto-grants-2013_06
Patent number
US08470847B2

Reaction notes

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