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

HRID 1498013Notes

Reaction equation

HRID 1498013 reaction equation
[NH:1]1[CH2:4][CH2:3][CH2:2]1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:11][C:12]1[N:20]2[C:15]([C:16](N3C=NC=N3)=[N:17][CH:18]=[N:19]2)=[C:14]([C:26]2[CH:27]=[N:28][N:29]([CH3:38])[C:30]=2[C:31]2[CH:36]=[CH:35][C:34]([CH3:37])=[CH:33][CH:32]=2)[N:13]=1>CN(C)C=O.C(OCC)(=O)C>[N:1]1([C:16]2[C:15]3=[C:14]([C:26]4[CH:27]=[N:28][N:29]([CH3:38])[C:30]=4[C:31]4[CH:36]=[CH:35][C:34]([CH3:37])=[CH:33][CH:32]=4)[N:13]=[C:12]([CH3:11])[N:20]3[N:19]=[CH:18][N:17]=2)[CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 10422AzetidineHCID 10796Cesium carbonateHCID 681821117-methyl-5-[1-methyl-5-(4-methylphenyl)-1H-pyrazol-4-yl]-4-(1H-1,2,4-triazol-1-yl)imidazo[5,1-f][1,2,4]triazine

Product 1

HCID 601632514-(azetidin-1-yl)-7-methyl-5-[1-methyl-5-(4-methylphenyl)-1H-pyrazol-4-yl]imidazo[5,1-f][1,2,4]triazine

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Azetidine (27.0 μL, 0.400 mmol) and cesium carbonate (97%, 202 mg, 0.601 mmol) were added to a solution of 7-methyl-5-[1-methyl-5-(4-methylphenyl)-1H-pyrazol-4-yl]-4-(1H-1,2,4-triazol-1-yl)imidazo[5,1-f][1,2,4]triazine (material from the previous reaction, ≦0.16 mmol) in N,N-dimethylformamide (3.0 mL), and the reaction mixture was stirred for 1 hour at room temperature. The reaction was diluted with ethyl acetate, washed with water, washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification using silica gel chromatography (Gradient: 0% to 5% methanol in dichloromethane), followed by azeotroping with heptane, provided the product as a white solid. Yield: 35 mg, 0.097 mmol, 61% over 2 steps. LCMS m/z 360.2 (M+1). 1H NMR (400 MHz, CDCl3) δ 2.20-2.28 (m, 2H), 2.35 (s, 3H), 2.64 (s, 3H), 3.5-3.9 (v br m, 2H), 3.90 (s, 3H), 3.9-4.3 (v br m, 2H), 7.21 (AB quartet, JAB=8.1 Hz, ΔvAB=32.1 Hz, 4H), 7.64 (s, 1H), 7.78 (s, 1H).

Workup

  1. washwashed with water
  2. washwashed with saturated aqueous sodium chloride solution
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification
  7. customby azeotroping with heptane

Sources & evidence

ORD record
ord-416bb40a6ee94cdb867af9b8b6f95035
Source dataset
uspto-grants-2015_12
Patent number
US09200000B2

Reaction notes

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