Cesium carbonate → 2-(1-Methyl-1h-pyrazol-4-yl)-4-[(6-nitro-3-pyridinyl)oxy]pyridine

HRID 2278884Notes

Reaction equation

HRID 2278884 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.[CH3:18][N:19]1[CH:23]=[C:22](B2OC(C)(C)C(C)(C)O2)[CH:21]=[N:20]1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:18][N:19]1[CH:23]=[C:22]([C:2]2[CH:7]=[C:6]([O:8][C:9]3[CH:10]=[N:11][C:12]([N+:15]([O-:17])=[O:16])=[CH:13][CH:14]=3)[CH:5]=[CH:4][N:3]=2)[CH:21]=[N:20]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 593227792-Chloro-4-((6-nitropyridin-3-yl)oxy)pyridine

Product 1

HCID 904029412-(1-Methyl-1h-pyrazol-4-yl)-4-[(6-nitro-3-pyridinyl)oxy]pyridineYield 72.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A suspension of Example A1 (14.38 g, 57.1 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (13.08 g, 62.9 mmol) and Cs2CO3 (55.9 g, 171 mmol) in DMF (150 mL) was sparged with Ar, treated with Pd(PPh3)4 (6.60 g, 5.71 mmol), sparged again with Ar and heated at 90° C. overnight. The mixture was cooled to RT, the solids removed via filtration through diatomaceous earth, washed with EtOAc and the filtrate concentrated to near-dryness. The residue was treated with EtOAc, washed with 5% LiCl (1×) and the aqueous layer back-extracted with EtOAc (4×). The combined organics were dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM) to afford 2-(1-methyl-1H-pyrazol-4-yl)-4-((6-nitropyridin-3-yl)oxy)pyridine (12.28 g, 72%). 1H NMR (400 MHz, DMSO-d6): δ 8.59 (d, J=2.8 Hz, 1 H), 8.49 (d, J=5.6 Hz, 1 H), 8.41 (d, J=8.9 Hz, 1 H), 8.29 (s, 1 H), 8.00 (d, J=0.7 Hz, 1 H), 7.97 (dd, J=8.9, 2.8 Hz, 1 H), 7.44 (d, J=2.4 Hz, 1 H), 6.97 (dd, J=5.6, 2.4 Hz, 1 H), 3.85 (s, 3 H); MS (ESI) m/z: 298.1 (M+H+).

Workup

  1. customsparged again with Ar
  2. temperatureThe mixture was cooled to RT
  3. customthe solids removed via filtration through diatomaceous earth
  4. washwashed with EtOAc
  5. concentrationthe filtrate concentrated to near-dryness
  6. additionThe residue was treated with EtOAc
  7. washwashed with 5% LiCl (1×)
  8. extractionthe aqueous layer back-extracted with EtOAc (4×)
  9. dry with materialThe combined organics were dried over Na2SO4
  10. concentrationconcentrated to dryness
  11. custompurified via silica gel chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-984985d927014243b0df75d8e1829b1e
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

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