1H-Pyrazole, 4-chloro- → 5-((1H-1,2,4-Triazol-1-yl)methyl)-3-(4-chloro-1H-Pyrazol-1-yl)-2-methoxypyridine

HRID 2271492Notes

Reaction equation

[N:1]1([CH2:6][C:7]2[CH:8]=[C:9](Br)[C:10]([O:13][CH:14](F)F)=[N:11][CH:12]=2)[CH:5]=[N:4][CH:3]=[N:2]1.CC(C)([O-])C.[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1.[Cl:52][C:53]1[CH:54]=[N:55][NH:56][CH:57]=1>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[N:1]1([CH2:6][C:7]2[CH:8]=[C:9]([N:55]3[CH:54]=[C:53]([Cl:52])[CH:57]=[N:56]3)[C:10]([O:13][CH3:14])=[N:11][CH:12]=2)[CH:5]=[N:4][CH:3]=[N:2]1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 5-((1H-1,2,4-triazol-1-yl)methyl)-3-Bromo-2-methoxypyridine (Intermediate 13), (100 mg, 0.37 mmol), in toluene (5 mL) was added tris(dibenzylideneacetone)dipalladium(0) (34.1 mg, 0.04 mmol), sodium tert-butoxide (71.6 mg, 0.74 mmol), (2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (29.3 mgs, 0.07 mmol) and 4-chloro-1H-pyrazole (37.3 mg, 0.37 mmol). The mixture was heated at 100° C. for 30 min. The mixture was quenched with water (0.5 mL), diluted with ethyl acetate (10 mL), dried (Na2SO4), filtered and concentrated under reduced pressure. Purification (FCC, SiO2, 20-100% EtOAc/hexanes) afforded the title compound (50 mg, 46%). 1H NMR (400 MHz, DMSO-d6) δ 8.69 (s, 1H), 8.07 (s, 2H), 8.01 (q, J=2.3 Hz, 2H), 7.99 (s, 1H), 5.37 (s, 2H), 3.94 (s, 3H), 2.52 (s, 1H). [M+H]=292.12.

Workup

customThe mixture was quenched with water (0.5 mL)
additiondiluted with ethyl acetate (10 mL)
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated under reduced pressure
customPurification (FCC, SiO2, 20-100% EtOAc/hexanes)

Sources & evidence

ORD record: ord-3f1a38a77a344ab1b5dc94ffde1d7014
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09120770B2

Reaction notes

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