Azetidine → HCID 68181924, compound

HRID 1498049Notes

Reaction equation

HRID 1498049 reaction equation
P(Cl)(Cl)(Cl)=O.[Br:6][C:7]1[N:11]([CH3:12])[N:10]=[CH:9][C:8]=1[C:13]1[N:14]=[CH:15][N:16]2[C:21]=1[C:20](=O)[NH:19][CH:18]=[N:17]2.C([N:26]([CH2:30][CH3:31])[CH:27](C)C)(C)C.N1CCC1>C1(C)C=CC=CC=1>[N:26]1([C:20]2[C:21]3=[C:13]([C:8]4[CH:9]=[N:10][N:11]([CH3:12])[C:7]=4[Br:6])[N:14]=[CH:15][N:16]3[N:17]=[CH:18][N:19]=2)[CH2:27][CH2:31][CH2:30]1

Participants

6

Reactant 4

HCID 10422AzetidineHCID 24813Phosphorus oxychlorideHCID 81531DiisopropylethylamineHCID 136350285HCID 136350285, compound

Product 1

HCID 68181924HCID 68181924, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Phosphorus oxychloride (0.046 mL, 0.503 mmol) was added to a mixture of 5-(5-bromo-1-methyl-1H-pyrazol-4-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one (50 mg, 0.17 mmol) in toluene (1 mL). After addition of N,N-diisopropylethylamine (99.5%, 0.149 mL, 0.84 mmol), the reaction was allowed to stir at room temperature for 18 hours. After removal of solvent in vacuo, the residue was dissolved in dichloromethane and treated with azetidine (0.023 mL, 0.34 mmol). After 66 hours, the reaction was concentrated under reduced pressure and the residue was purified by silica gel chromatography (Gradient: 0% to 10% methanol in ethyl acetate) to provide C8. Yield: 25 mg, 0.075 mmol, 44%. LCMS m/z 336.1 (M+1). 1H NMR (400 MHz, CD3OD) δ 2.26-2.34 (m, 2H), 3.5-4.4 (v br m, 4H), 3.97 (s, 3H), 7.70 (s, 1H), 7.84 (s, 1H), 8.47 (s, 1H).

Workup

  1. customAfter removal of solvent in vacuo
  2. dissolutionthe residue was dissolved in dichloromethane
  3. waitAfter 66 hours
  4. concentrationthe reaction was concentrated under reduced pressure
  5. customthe residue was purified by silica gel chromatography (Gradient: 0% to 10% methanol in ethyl acetate)

Sources & evidence

ORD record
ord-ebad8900d03c4e8e9ab6fa1dac48f54c
Source dataset
uspto-grants-2015_12
Patent number
US09200000B2

Reaction notes

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