Dimethylformamide → 4-(azetidin-1-yl)-5-[5-(4-methoxy-2-methylphenyl)-1-methyl-1H-pyrazol-4-yl]-7-methylimidazo[5,1-f][1,2,4]triazine

HRID 1907207Notes

Reaction equation

HRID 1907207 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.[CH3:22][O:23][C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[C:26]([CH3:33])[CH:25]=1.O.O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CN(C)C=O>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.O>[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:27]4[CH:28]=[CH:29][C:24]([O:23][CH3:22])=[CH:25][C:26]=4[CH3:33])[N:12]=[C:13]([CH3:14])[N:9]3[N:8]=[CH:7][N:6]=2)[CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 2773486(4-Methoxy-2-methylphenyl)boronic acidHCID 23436936Potassium phosphate dihydrateHCID 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 681818834-(azetidin-1-yl)-5-[5-(4-methoxy-2-methylphenyl)-1-methyl-1H-pyrazol-4-yl]-7-methylimidazo[5,1-f][1,2,4]triazine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

4-(Azetidin-1-yl)-5-(5-bromo-1-methyl-1H-pyrazol-4-yl)-7-methylimidazo[5,1-f][1,2,4]triazine (200 mg, 0.574 mmol) was combined with (4-methoxy-2-methylphenyl)boronic acid (180 mg, 1.08 mmol), potassium phosphate dihydrate (98%, 571 mg, 2.25 mmol), tetrakis(triphenylphosphine)palladium(0) (99.9%, 65.9 mg, 0.057 mmol) and N,N-dimethylformamide (12 mL) and heated in a microwave reactor at 150° C. for 60 minutes. This reaction mixture was combined with crude reaction products from three other identical reactions, and poured into water. The mixture was extracted with ethyl acetate, and the combined organic layers were washed with water, then with saturated aqueous sodium chloride solution. After drying over sodium sulfate, the organic extracts were filtered and concentrated in vacuo. Purification via silica gel chromatography (Eluants: heptane/ethyl acetate/methanol mixtures, 90:15:10 followed by 60:30:10, 45:55:10, 30:70:10 ratios) provided the product as a solid. Combined yield: 508 mg, 1.30 mmol, 56%. LCMS m/z 390.2 (M+1). 1H NMR (400 MHz, CDCl3) δ 2.08 (s, 3H), 2.26-2.35 (m, 2H), 2.60 (s, 3H), 3.69 (s, 3H), 3.79 (s, 3H), 3.8-4.2 (v br m, 4H), 6.72-6.76 (m, 2H), 7.17-7.24 (br m, 1H), 7.67 (s, 1H), 7.78 (s, 1H).

Workup

  1. customreaction products from three other identical reactions
  2. extractionThe mixture was extracted with ethyl acetate
  3. washthe combined organic layers were washed with water
  4. dry with materialAfter drying over sodium sulfate
  5. filtrationthe organic extracts were filtered
  6. concentrationconcentrated in vacuo
  7. customPurification via silica gel chromatography (Eluants: heptane/ethyl acetate/methanol mixtures, 90:15:10 followed by 60:30:10, 45:55:10, 30:70:10 ratios)

Sources & evidence

ORD record
ord-40aa3521728044c393a35195f3151bc4
Source dataset
uspto-grants-2013_12
Patent number
US08598155B2

Reaction notes

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