Cesium carbonate → HCID 57411677, compound

HRID 1502385Notes

Reaction equation

HRID 1502385 reaction equation
Cl[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:14]3[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=3[CH3:21])[N+:8]([O-:13])=[C:9]2[CH3:12])=[CH:4][N:3]=1.[CH:22]1([C:25]([NH2:27])=[O:26])[CH2:24][CH2:23]1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.ClCCl.CO>[CH:22]1([C:25]([NH:27][C:2]2[CH:11]=[C:10]3[C:5]([CH:6]=[C:7]([C:14]4[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=4[CH3:21])[N+:8]([O-:13])=[C:9]3[CH3:12])=[CH:4][N:3]=2)=[O:26])[CH2:24][CH2:23]1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 80376CyclopropanecarboxamideHCID 86674960HCID 86674960, compound

Product 1

HCID 57411677HCID 57411677, compoundYield 100%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 7-chloro-3-(5-fluoro-2-methylphenyl)-1-methyl-2,6-naphthyridine 2-oxide (350 mg, 1.2 mmol), cyclopropanecarboxamide (295 mg, 3.5 mmol), Chloro[2-(dicyclohexylphosphino)-3-,6-dimethoxy-2,4′-6′-tri-i-pr-1,1′-biphenyl)][2-(2-aminoethyl) Ph]Pd(II) (46 mg, 0.06 mmol), (dicyclohexylphosphino)-3-,6-dimethoxy-2,4′-6′-tri-i-pr-1,1′-biphenyl (120 mg, 0.2 mmol), and cesium carbonate (750 mg, 2.3 mmol) in 1,4-dioxane (5 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 (400 mg, 100%). 1H NMR (400 MHz, DMSO) δ 11.16 (s, 1H), 9.11 (s, 1H), 8.56 (s, 1H), 8.02 (s, 1H), 7.41-7.31 (m, 1H), 7.22 (m, 2H), 2.66 (s, 3H), 2.10 (m, 1H), 2.08 (s, 3H), 0.94-0.81 (m, 4H). LCMS (Method D): RT=11.358 min, M+H+=352.1.

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-b1d0c326c2c640ef80a8ef9dc6687e55
Source dataset
uspto-grants-2015_12
Patent number
US09206175B2

Reaction notes

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