5-Chloro-3-fluoro-2-(trimethylstannyl)pyridine → 4-(azetidin-1-yl)-5-[5-(5-chloro-3-fluoropyridin-2-yl)-1-methyl-1H-pyrazol-4-yl]-7-methylimidazo[5,1-f][1,2,4]triazine

HRID 1907211Notes

Reaction equation

HRID 1907211 reaction equation
[N:1]1([C:5]2[C:10]3=[C:11]([C:15]4[CH:16]=[N:17][N:18]([CH3:21])[C:19]=4Br)[N:12]=[C:13]([CH3:14])[N:9]3[N:8]=[CH:7][N:6]=2)[CH2:4][CH2:3][CH2:2]1.[Cl:22][C:23]1[CH:24]=[C:25]([F:33])[C:26]([Sn](C)(C)C)=[N:27][CH:28]=1>C1(C)C=CC=CC=1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[N:1]1([C:5]2[C:10]3=[C:11]([C:15]4[CH:16]=[N:17][N:18]([CH3:21])[C:19]=4[C:26]4[C:25]([F:33])=[CH:24][C:23]([Cl:22])=[CH:28][N:27]=4)[N:12]=[C:13]([CH3:14])[N:9]3[N:8]=[CH:7][N:6]=2)[CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 2

HCID 681820735-Chloro-3-fluoro-2-(trimethylstannyl)pyridineHCID 681820804-(azetidin-1-yl)-5-(5-bromo-1-methyl-1H-pyrazol-4-yl)-7-methylimidazo[5,1-f][1,2,4]triazine

Product 1

HCID 681818674-(azetidin-1-yl)-5-[5-(5-chloro-3-fluoropyridin-2-yl)-1-methyl-1H-pyrazol-4-yl]-7-methylimidazo[5,1-f][1,2,4]triazine

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

4-(Azetidin-1-yl)-5-(5-bromo-1-methyl-1H-pyrazol-4-yl)-7-methylimidazo[5,1-f][1,2,4]triazine (35 mg, 0.10 mmol) and 5-chloro-3-fluoro-2-(trimethylstannyl)pyridine (59.5 mg, 0.202 mmol) were combined in toluene (1 mL) in a sealable tube and treated with dichlorobis(triphenylphosphine)palladium(II) (99%, 3.50 mg, 0.0050 mmol). The tube was sealed, and the reaction mixture was heated at 120° C. for 24 hours. The reaction was cooled, filtered through Celite and the pad was washed with ethyl acetate. After removal of solvent from the filtrate under reduced pressure, the residue was purified via silica gel chromatography (Eluant: 1% methanol in ethyl acetate) to provide the product as a solid. Yield: 20 mg, 0.050 mmol, 50%. LCMS m/z 399.1 (M+1). 1H NMR (400 MHz, CDCl3) δ 2.21-2.30 (m, 2H), 2.59 (s, 3H), 3.86-4.14 (br m, 4H), 3.98 (s, 3H), 7.40 (dd, J=9.0, 2.0 Hz, 1H), 7.72 (s, 1H), 7.80 (s, 1H), 8.51-8.53 (m, 1H).

Workup

  1. customThe tube was sealed
  2. temperatureThe reaction was cooled
  3. filtrationfiltered through Celite
  4. washthe pad was washed with ethyl acetate
  5. customAfter removal of solvent from the filtrate under reduced pressure
  6. customthe residue was purified via silica gel chromatography (Eluant: 1% methanol in ethyl acetate)

Sources & evidence

ORD record
ord-98a57a97f30b46faa8322ec0813d2cfd
Source dataset
uspto-grants-2013_12
Patent number
US08598155B2

Reaction notes

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