Cesium carbonate → 1,1-Dimethylethyl (2-{4-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]-1-piperazinyl}ethyl)carbamate

HRID 1787687Notes

Reaction equation

HRID 1787687 reaction equation
Br[C:2]1[C:3]([F:14])=[CH:4][N:5]=[C:6]2[C:11]=1[N:10]=[C:9]([O:12][CH3:13])[CH:8]=[CH:7]2.[N:15]1([CH2:21][CH2:22][NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1.C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:14][C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:2]=1[N:18]1[CH2:19][CH2:20][N:15]([CH2:21][CH2:22][NH:23][C:24](=[O:30])[O:25][C:26]([CH3:28])([CH3:27])[CH3:29])[CH2:16][CH2:17]1)=[N:10][C:9]([O:12][CH3:13])=[CH:8][CH:7]=2

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 15144011-(2-N-Boc-aminoethyl)piperazineHCID 454803208-Bromo-7-fluoro-2-methoxy-1,5-naphthyridine

Product 1

HCID 575995761,1-Dimethylethyl (2-{4-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]-1-piperazinyl}ethyl)carbamateYield 41.6%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

In a sealed tube, 8-bromo-7-fluoro-2-(methyloxy)-1,5-naphthyridine (1.1 g, 4.3 mmol), 1,1-dimethylethyl [2-(1-piperazinyl)ethyl]carbamate (1 g, 4.3 mmol), Pd2dba3 (271 mg, 0.262 mmol), rac-Binap (163 mg, 0.262 mmol), Cs2CO3 (2.98 mg, 9.2 mmol) and 18-C-6 (115 mg, 0.436 mmol) in dioxane (22 mL) were combined and flushed with N2. After 15 min, the tube was sealed and heated to 100° C. while stirring rapidly. After 12 h, the solution was filtered, concentrated and the residue purified via column chromatography (silica, 1% MeOH in DCM (1% NH4OH)) yielding the title compound (725 mg, 41%) as an orange oil: LCMS (ES) m/e 406 (M+H)+.

Workup

  1. customflushed with N2
  2. customthe tube was sealed
  3. waitAfter 12 h
  4. filtrationthe solution was filtered
  5. concentrationconcentrated
  6. customthe residue purified via column chromatography (silica, 1% MeOH in DCM (1% NH4OH))

Sources & evidence

ORD record
ord-3c2b57db026d4b52aa151ef77a6cd671
Source dataset
uspto-grants-2009_03
Patent number
US07511035B2

Reaction notes

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