Propynamide → 3-(9-Bromo-6-isopropyl-1-oxo-1,2-dihydrobenzo[c]-1,6-naphthyridin-4-yl)prop-2-ynamide

HRID 2193022Notes

Reaction equation

HRID 2193022 reaction equation
[Br:1][C:2]1[CH:20]=[CH:19][C:5]2[C:6]([CH:16]([CH3:18])[CH3:17])=[N:7][C:8]3[C:9](I)=[CH:10][NH:11][C:12](=[O:14])[C:13]=3[C:4]=2[CH:3]=1.[C:21]([NH2:25])(=[O:24])[C:22]#[CH:23]>[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CN(C=O)C>[Br:1][C:2]1[CH:20]=[CH:19][C:5]2[C:6]([CH:16]([CH3:18])[CH3:17])=[N:7][C:8]3[C:9]([C:23]#[C:22][C:21]([NH2:25])=[O:24])=[CH:10][NH:11][C:12](=[O:14])[C:13]=3[C:4]=2[CH:3]=1

Participants

6

Reactant 2

HCID 101445PropynamideHCID 593756199-bromo-4-iodo-6-isopropylbenzo[c]-1,6-naphthyridin-1(2H)-one

Product 1

HCID 593756833-(9-Bromo-6-isopropyl-1-oxo-1,2-dihydrobenzo[c]-1,6-naphthyridin-4-yl)prop-2-ynamide

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

9-bromo-4-iodo-6-isopropylbenzo[c]-1,6-naphthyridin-1(2H)-one (140 mg, 0.32 mmol), propynoic acid amide (26 mg, 0.38 mmol), copper (I) iodide (9.0 mg, 0.047 mmol), and Pd(Ph3P)4 (37 mg, 0.032 mmol) were added to a vial, followed by DMF (1.5 ml) and TEA (0.13 ml, 0.95 mmol). The resulting suspension was purged with argon (subsurface bubbling) for 10 min, and then stirred for 15 hr at room temperature. The reaction mixture was diluted with DMF and purified directly by reverse phase preparative HPLC using an acetonitrile/water (with 0.05% TFA as a modifier) gradient to afford 3-(9-bromo-6-isopropyl-1-oxo-1,2-dihydrobenzo[c]-1,6-naphthyridin-4-yl)prop-2-ynamide. 1H NMR (500 MHz, DMSO-D6) δ 12.33 (br s, 1H), 10.21 (d, 1H), 8.46 (d, 1H), 8.04 (s, 1H), 7.93 (dd, 1H), 7.91 (br s, 1H), 7.58 (s, 1H), 4.07 (septet, 1H), 1.40 (d, 61-1). LRMS (ESI) calc'd for (C18H14BrN3O2) [M+H]+, 384.0; found 384.0.

Workup

  1. customThe resulting suspension was purged with argon (subsurface bubbling) for 10 min
  2. additionThe reaction mixture was diluted with DMF
  3. custompurified directly by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-53174745f9c545498ee2db1fc66cf441
Source dataset
uspto-grants-2012_12
Patent number
US08329722B2

Reaction notes

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