Cesium carbonate → 6-[4-Isopropyl-2-(2-trifluoromethoxy-phenyl)-2H-pyrazol-3-ylmethoxy]-2-methyl-3-nitro-pyridine

HRID 2261743Notes

Reaction equation

[CH:1]([C:4]1[CH:8]=[N:7][N:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[O:15][C:16]([F:19])([F:18])[F:17])[C:5]=1[CH2:20][OH:21])([CH3:3])[CH3:2].Cl[C:23]1[N:28]=[C:27]([CH3:29])[C:26]([N+:30]([O-:32])=[O:31])=[CH:25][CH:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C(P(C(C)(C)C)C1C=CC2C(=CC=CC=2)C=1C1C2C(=CC=CC=2)C=CC=1)(C)(C)C>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:1]([C:4]1[CH:8]=[N:7][N:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[O:15][C:16]([F:17])([F:18])[F:19])[C:5]=1[CH2:20][O:21][C:23]1[N:28]=[C:27]([CH3:29])[C:26]([N+:30]([O-:32])=[O:31])=[CH:25][CH:24]=1)([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 70 °C

Procedure

To an ambient temperature solution of [4-Isopropyl-2-(2-trifluoromethoxy-phenyl)-2H-pyrazol-3-yl]-methanol (2.0 g, 6.66 mmol) in degassed toluene (22 mL) is added 6-Chloro-2-methyl-3-nitro-pyridine (1.15 g, 6.66 mmol), cesium carbonate (3.25 g, 9.99 mmol), 2-(Di-t-butylphosphino)-1,1′-binapthyl (332 mg, 0.833 mmol, 12.5 mol %), and palladium (II) acetate (150 mg, 0.666 mmol, 10 mol %). The reaction mixture is heated to 70° C. overnight. The reaction mixture is filtered through a pad of Celite®, is concentrated under reduced pressure, and is chromatographed (0% to 20% EtOAc/Hex) to yield the title compound (2.73 g, 94%). 1H NMR (400 MHz, CDCl3) δ 8.22 (d, 1H, J=8.8 Hz), 7.64 (s, 1H), 7.52 (dd, 1H, J=7.8, 1.7 Hz), 7.49-7.44 (m, 1H), 7.41-7.34 (m, 2H), 6.51 (d, 1H, J=9.2 Hz), 5.35 (s, 2H), 3.05 (sept, 1H, J=7.0 Hz), 2.72 (s, 3H), 1.29 (d, 6H, J=7.0 Hz).

Workup

filtrationThe reaction mixture is filtered through a pad of Celite®
concentrationis concentrated under reduced pressure
customis chromatographed (0% to 20% EtOAc/Hex)

Sources & evidence

ORD record: ord-7bc67b539e8a42c484de20524ecb82c3
Source dataset: uspto-grants-2010_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07846960B2

Reaction notes

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