Cesium carbonate → 7-(Tert-butoxycarbonylamino)-3-(5-fluoro-4-methylpyridin-3-yl)-2,6-naphthyridine 2-oxide

HRID 1502472Notes

Reaction equation

HRID 1502472 reaction equation
Cl[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:13]3[CH:14]=[N:15][CH:16]=[C:17]([F:20])[C:18]=3[CH3:19])[N+:8]([O-:12])=[CH:9]2)=[CH:4][N:3]=1.[C:21](=[O:28])([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[NH2:22].C1(P(C2CCCCC2)C2C(OC)=CC=C(OC)C=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.ClCCl.CO>[C:24]([O:23][C:21]([NH:22][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:13]3[CH:14]=[N:15][CH:16]=[C:17]([F:20])[C:18]=3[CH3:19])[N+:8]([O-:12])=[CH:9]2)=[CH:4][N:3]=1)=[O:28])([CH3:27])([CH3:26])[CH3:25]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 77922tert-Butyl carbamateHCID 25112535BrettphosHCID 866749847-Chloro-3-(5-fluoro-4-methylpyridin-3-yl)-2,6-naphthyridine 2-oxide

Product 1

HCID 711152257-(Tert-butoxycarbonylamino)-3-(5-fluoro-4-methylpyridin-3-yl)-2,6-naphthyridine 2-oxideYield 38%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 7-chloro-3-(5-fluoro-4-methylpyridin-3-yl)-2,6-naphthyridine 2-oxide (150 mg, 0.52 mmol), tert-butyl carbamate (121 mg, 1.04 mmol), 2-(dicyclohexylphosphino)3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl (58 mg, 0.10 mmol), chloro[2-(dicyclohexylphosphino)-3,6-dimethoxy-2′-4′-6′-tri-1-propyl-1,1′-biphenyl][2-(2-aminoethyl)phenyl]palladium(II) (42 mg, 0.052 mmol), and cesium carbonate (341 mg, 1.04 mmol) in dioxane (2.5 mL) was heated at 100° C. for 8 hours in a vial sealed with a Teflon cap. The reaction mixture was diluted with dichloromethane (50 mL) and methanol (5 mL), filtered over Celite, and concentrated in vacuo to provide a residue that was purified by flash chromatography (12 g, Silica, 0-10% methanol in dichloromethane). Desired fractions were combined and evaporated in vacuo to afford the title compound as a yellow solid (73 mg, 38%). 1H NMR (400 MHz, DMSO) δ 10.16 (s, 1H), 9.14 (s, 1H), 9.08 (s, 1H), 8.62 (s, 1H), 8.39 (s, 1H), 8.21 (s, 1H), 8.16 (s, 1H), 1.52 (s, 9H).

Workup

  1. customcap
  2. filtrationfiltered over Celite
  3. concentrationconcentrated in vacuo
  4. customto provide a residue that
  5. customwas purified by flash chromatography (12 g, Silica, 0-10% methanol in dichloromethane)
  6. customevaporated in vacuo

Sources & evidence

ORD record
ord-daaa0751911b4207bb5dc9326b1d3e78
Source dataset
uspto-grants-2015_12
Patent number
US09206175B2

Reaction notes

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