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

HRID 2356331Notes

Reaction equation

HRID 2356331 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.CC([N:19]([CH2:23][CH2:24][N:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1)[C:20](=[O:22])[O-:21])(C)C.C1C=CC(P([C:44]2C=CC3[C:46](=CC=CC=3)[C:45]=2[C:54]2C3C(=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:28]1[CH2:27][CH2:26][N:25]([CH2:24][CH2:23][NH:19][C:20](=[O:22])[O:21][C:45]([CH3:54])([CH3:46])[CH3:44])[CH2:30][CH2:29]1)=[N:10][C:9]([O:12][CH3:13])=[CH:8][CH:7]=2

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 454803208-Bromo-7-fluoro-2-methoxy-1,5-naphthyridineHCID 53422674Tert-butyl2-(piperazin-1-yl)ethylcarbamate

Product 1

HCID 575995761,1-Dimethylethyl (2-{4-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]-1-piperazinyl}ethyl)carbamateYield 682.5%

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-76ac40439372419c9fa20890c557afe6
Source dataset
uspto-grants-2010_07
Patent number
US07759340B2

Reaction notes

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