Cesium carbonate → 3-(2-Chlorophenyl)-7-(cyclopropanecarboxamido)-2,6-naphthyridine 2-oxide

HRID 468852Notes

Reaction equation

HRID 468852 reaction equation
Cl[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[Cl:19])[N+:8]([O-:12])=[CH:9]2)=[CH:4][N:3]=1.[CH:20]1([C:23]([NH2:25])=[O:24])[CH2:22][CH2:21]1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.ClCCl.CO>[Cl:19][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[C:7]1[N+:8]([O-:12])=[CH:9][C:10]2[C:5]([CH:6]=1)=[CH:4][N:3]=[C:2]([NH:25][C:23]([CH:20]1[CH2:22][CH2:21]1)=[O:24])[CH:11]=2

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 80376CyclopropanecarboxamideHCID 866749517-Chloro-3-(2-chlorophenyl)-2,6-naphthyridine 2-oxide

Product 1

HCID 679746713-(2-Chlorophenyl)-7-(cyclopropanecarboxamido)-2,6-naphthyridine 2-oxideYield 84.1%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 7-chloro-3-(2-chlorophenyl)-2,6-naphthyridine 2-oxide (2.0 g, 7.0 mmol), cyclopropanecarboxamide (653 mg, 7.7 mmol), Chloro[2-(dicyclohexylphosphino)-3-,6-dimethoxy-2,4′-6′-tri-1-pr-1,1′-biphenyl)][2-(2-aminoethyl)Ph]Pd(II) (167 mg, 0.21 mmol), (dicyclohexylphosphino)-3-,6-dimethoxy-2,4′-6′-tri-1-pr-1,1′-biphenyl (281 mg, 0.52 mmol), and cesium carbonate (4.5 g, 13.9 mmol) in 1,4-dioxane (19 mL) was heated at 90° C. for 4 hours. The cooled reaction mixture was diluted with dichloromethane (200 mL) and methanol (100 mL), mixed with Celite, filtered, the solids washed with 15% methanol/dichloromethane (2×100 mL), and the filtrate was dried over sodium sulfate, filtered, and evaporated in vacuo to afford a residue that was purified by flash chromatography (silica, 40 g, ISCO, 0-10% methanol in dichloromethane) to afford the title compound as an off-white solid (2.0 g, 84%). 1H NMR (400 MHz, DMSO) δ 11.15 (s, 1H), 9.13 (s, 1H), 9.09 (s, 1H), 8.42 (s, 1H), 8.17 (s, 1H), 7.62 (m, 1H), 7.58-7.45 (m, 3H), 2.14-2.03 (m, 1H), 0.91-0.82 (m, 4H). LCMS (Method G): RT=8.18 min, M+H+=340.0.

Workup

  1. customThe cooled reaction mixture
  2. additionmixed with Celite
  3. filtrationfiltered
  4. washthe solids washed with 15% methanol/dichloromethane (2×100 mL)
  5. dry with materialthe filtrate was dried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customto afford a residue that
  9. customwas purified by flash chromatography (silica, 40 g, ISCO, 0-10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-0bbc545e8cd54ed2a92b0eae24e2d21c
Source dataset
uspto-grants-2014_01
Patent number
US08623889B2

Reaction notes

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