Cesium carbonate → N-(4-((6-nitropyridin-3-yl)oxy)pyridin-2-yl)cyclopropanecarboxamide

HRID 626504

Reaction equation

HRID 626504 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[N:11][C:12]([N+:15]([O-:17])=[O:16])=[CH:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].[CH:24]1([C:27]([NH2:29])=[O:28])[CH2:26][CH2:25]1>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].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>[N+:15]([C:12]1[N:11]=[CH:10][C:9]([O:8][C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:29][C:27]([CH:24]3[CH2:26][CH2:25]3)=[O:28])[CH:7]=2)=[CH:14][CH:13]=1)([O-:17])=[O:16]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 80376CyclopropanecarboxamideHCID 593227792-Chloro-4-((6-nitropyridin-3-yl)oxy)pyridine

Product 1

HCID 90410505N-(4-((6-nitropyridin-3-yl)oxy)pyridin-2-yl)cyclopropanecarboxamideYield 64%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylCatalystHCID 312751,4-DioxaneSolvent

Procedure

A suspension of Example A1 (2.00 g, 7.95 mmol), Cs2CO3 (5.00 g, 15.35 mmol), XPhos (0.200 g, 0.420 mmol), Pd2(dba)3 (0.200 g, 0.218 mmol) and cyclopropylcarboxamide (1.00 g, 11.75 mmol) in dioxane (20 mL) was heated at 90° C. under argon overnight. The mixture was cooled to RT and the solids removed via filtration and washed with DCM and THF. The filtrate was concentrated to dryness and purified via silica gel chromatography (EtOAc/Hex) to afford N-(4-((6-nitropyridin-3-yl)oxy)pyridin-2-yl)cyclopropanecarboxamide (1.52 g, 64%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.01 (s, 1H), 8.57 (dd, J=2.8, 0.5 Hz, 1H), 8.40 (m, 1H), 8.31 (d, J=5.7 Hz, 1H), 7.98 (dd, J=8.9, 2.8 Hz, 1H), 7.85 (d, J=2.4 Hz, 1H), 6.89 (dd, J=5.7, 2.4 Hz, 1H), 1.97 (m, 1H), 0.77 (m, 4H); MS (ESI) m/z: 301.1 (M+H+).

Workup

  1. customthe solids removed via filtration
  2. washwashed with DCM and THF
  3. concentrationThe filtrate was concentrated to dryness
  4. custompurified via silica gel chromatography (EtOAc/Hex)

Sources & evidence

ORD record
ord-a55ddaf05617467f95bcbe7d49fb3c62
Source dataset
uspto-grants-2016_04
Patent number
US09309224B2

Linked notes

Loading…