Tetrahydrofuran → 1-(1-(4-Cyanobenzyl)imidazole-5-ylmethyl)-4-(tert-butyloxycarbonyl)-(trans)2,5-dimethylpiperazine

HRID 277777Notes

Reaction equation

HRID 277777 reaction equation
[C:1]([C:3]1[CH:16]=[CH:15][C:6]([CH2:7][N:8]2[C:12]([CH:13]=O)=[CH:11][N:10]=[CH:9]2)=[CH:5][CH:4]=1)#[N:2].[CH3:17][C@H:18]1[CH2:23][N:22]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C@H:21]([CH3:31])[CH2:20][NH:19]1.O1CCCC1.C([BH3-])#N.[Na+]>CO.O.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].C(O)C>[C:1]([C:3]1[CH:16]=[CH:15][C:6]([CH2:7][N:8]2[C:12]([CH2:13][N:19]3[CH2:20][C@@H:21]([CH3:31])[N:22]([C:24]([O:26][C:27]([CH3:28])([CH3:30])[CH3:29])=[O:25])[CH2:23][C@@H:18]3[CH3:17])=[CH:11][N:10]=[CH:9]2)=[CH:5][CH:4]=1)#[N:2]

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 5003444Sodium cyanoborohydrideHCID 106322894-[(5-Formylimidazol-1-yl)methyl]benzonitrileHCID 24903576(2R,5S)-2,5-Dimethyl-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 701531721-(1-(4-Cyanobenzyl)imidazole-5-ylmethyl)-4-(tert-butyloxycarbonyl)-(trans)2,5-dimethylpiperazine

Reagents, catalysts & solvents 3

HCID 11026Titanium isopropoxideCatalystHCID 702EthanolSolventHCID 22242641Methanol--water (1/1)Solvent

Conditions

Temperature
60 °C

Procedure

To a round bottom flask were added 1-(4-cyanobenzyl)-5-formylimidazole (250.0 mg, 1.2 mmole) along with titanium(IV)isopropoxide (1.0 ml, 3.65 mmol), (trans) 2,5-Dimethyl-4-tertbutyloxycarbonylpiprizine (253.7 mg, 1.2 mmol) (prepared as described in Step 1), and tetrahydrofuran (0.4 ml). The reaction was heated at 60° C. for 1.25 hour. The reaction was cooled and sodiumcyanoborohydride (95.0 mg, 1.5 mmol) was added along with ethanol (0.5 ml) and the reaction was stirred at RT for 18 hours. The reaction was diluted with methanol/water (3 ml/1 ml) and the mixture filtered through celite. The filtrate was then concentrated to an oil, dissolved into methanol and put through a High Pressure Liquid Chromatography column. The desired fractions were collected, concentrated, and lyophilized to give the ditrifluoroacetic acid salt of the title compound.

Workup

  1. temperatureThe reaction was cooled
  2. filtrationthe mixture filtered through celite
  3. concentrationThe filtrate was then concentrated to an oil
  4. dissolutiondissolved into methanol
  5. customThe desired fractions were collected
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-746d9af315ab4fb7a69c9a5a5da08560
Source dataset
uspto-grants-2002_03
Patent number
US06358956B1

Reaction notes

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