Benzyl Bromide → 2-(1-Benzyl-4-methyl-pyrrolidin-3-yl)-7-(tetrahydro-pyran-4-yl)-3H-imidazo[5,1-f][1,2,4]triazin-4-one

HRID 57720Notes

Reaction equation

HRID 57720 reaction equation
[CH2:1]([N:8]1[CH2:12][CH:11]([CH3:13])[CH:10]([C:14]2[NH:19][C:18](=[O:20])[C:17]3=[CH:21][N:22]=[C:23](I)[N:16]3[N:15]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:25](=[O:28])([O-])[O-].[K+].[K+].[CH2:31](Br)[C:32]1C=CC=[CH:34][CH:33]=1>C(#N)C>[CH2:1]([N:8]1[CH2:12][CH:11]([CH3:13])[CH:10]([C:14]2[NH:19][C:18](=[O:20])[C:17]3=[CH:21][N:22]=[C:23]([CH:32]4[CH2:31][CH2:25][O:28][CH2:34][CH2:33]4)[N:16]3[N:15]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 1365928032-(1-Benzyl-4-methyl-pyrrolidin-3-yl)-7-iodo-3H-imidazo[5,1-f][1,2,4]triazin-4-one

Product 1

HCID 1360787662-(1-Benzyl-4-methyl-pyrrolidin-3-yl)-7-(tetrahydro-pyran-4-yl)-3H-imidazo[5,1-f][1,2,4]triazin-4-oneYield 25%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of compound 6 (70 mg, 0.296 mmol) and potassium carbonate (70 mg, 0.296 mmol) in acetonitrile (10 mL) was added benzyl bromide (70 mg, 0.296 mmol). The resulting solution was stirred at room temperature for 2 h. LC-MS showed that the reaction was complete. The reaction was quenched with water (40 mL), and the reaction mixture was extracted with CH2Cl2 (30 mL×3). The combined organic phases were washed with brine (30 mL), dried over Na2SO4 and concentrated in vacuum. The residue was purified by preparative TLC (CH2Cl2/MeOH=10:1) to afford the desired product (28.6 mg, 25% yield) as a white solid. LC-MS: m/z 394.2 [M+1]+. 1H NMR (400 MHz, CD3OD-d4): δ 7.60 (s, 1H), 7.29˜7.22 (m, 4H), 7.19˜7.17 (m, 1H), 3.95˜3.92 (m, 2H), 3.69˜3.58 (m, 2H), 3.52˜3.46 (m, 3H), 3.21 (m, 1H), 3.06˜3.04 (m, 1H), 2.91˜2.76 (m, 2H), 2.58˜2.56 (m, 1H), 2.16 (m, 1H), 1.89˜1.81 (m, 2H), 1.78 (m, 2H), 1.27 (d, J=6.8 Hz, 3H).

Workup

  1. customThe reaction was quenched with water (40 mL)
  2. extractionthe reaction mixture was extracted with CH2Cl2 (30 mL×3)
  3. washThe combined organic phases were washed with brine (30 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuum
  6. customThe residue was purified by preparative TLC (CH2Cl2/MeOH=10:1)

Sources & evidence

ORD record
ord-166a468fe4ca40bfa42992120f129fea
Source dataset
uspto-grants-2016_09
Patent number
US09434733B2

Reaction notes

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