Sodium cyanoborohydride → 2-methoxy-4-[2-(4-{[4-(1H-tetrazol-1-yl)phenyl]acetyl}piperazin-1-yl)ethyl]benzonitrile

HRID 2173444Notes

Reaction equation

HRID 2173444 reaction equation
[CH3:1][O:2][C:3]1[CH:10]=[C:9]([CH2:11][CH:12]=C)[CH:8]=[CH:7][C:4]=1[C:5]#[N:6].Cl.[N:15]1([C:21](=[O:34])[CH2:22][C:23]2[CH:28]=[CH:27][C:26]([N:29]3[CH:33]=[N:32][N:31]=[N:30]3)=[CH:25][CH:24]=2)[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1.C([BH3-])#N.[Na+]>CO.C(O)(=O)C>[CH3:1][O:2][C:3]1[CH:10]=[C:9]([CH2:11][CH2:12][N:18]2[CH2:17][CH2:16][N:15]([C:21](=[O:34])[CH2:22][C:23]3[CH:24]=[CH:25][C:26]([N:29]4[CH:33]=[N:32][N:31]=[N:30]4)=[CH:27][CH:28]=3)[CH2:20][CH2:19]2)[CH:8]=[CH:7][C:4]=1[C:5]#[N:6]

Participants

6

Reactant 3

HCID 5003444Sodium cyanoborohydrideHCID 666438682-(Methyloxy)-4-prop-2-en-1-ylbenzonitrileHCID 675172361-(piperazin-1-yl)-2-[4-(1H-tetrazol-1-yl)phenyl]ethanone hydrochloride

Product 1

HCID 573312372-methoxy-4-[2-(4-{[4-(1H-tetrazol-1-yl)phenyl]acetyl}piperazin-1-yl)ethyl]benzonitrile

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 887MethanolSolvent

Conditions

Temperature
-78 °C

Procedure

2-Methoxy-4-(prop-2-en-1-yl)benzonitrile (100 mg, 0.577 mmol) was dissolved in methanol (13 mL) and the resulting solution was cooled to −78° C. Ozone was bubbled through the solution until a blue color appeared (˜15 minutes). 1-(Piperazin-1-yl)-2-[4-(1H-tetrazol-1-yl)phenyl]ethanone hydrochloride (178 mg, 0.577 mmol) was added, followed by sodium cyanoborohydride (363 mg, 5.77 mmol). After stirring the reaction mixture for ˜5 minutes 3 drops of acetic acid were added and the mixture was permitted to warm to rt and stir for 2 h. The reaction mixture was concentrated to dryness, dissolved in EtOAc (40 mL) and washed with brine, saturated NaHCO3 solution. The organic layer was dried over Na2SO4, filtered and concentrated to dryness. The residue was then purified by mass directed HPLC to afford the title compound. LC/MS: [(M+1)]+=432.

Workup

  1. customOzone was bubbled through the solution until a blue color
  2. custom(˜15 minutes)
  3. additionwere added
  4. temperatureto warm to rt
  5. concentrationThe reaction mixture was concentrated to dryness
  6. dissolutiondissolved in EtOAc (40 mL)
  7. washwashed with brine, saturated NaHCO3 solution
  8. dry with materialThe organic layer was dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated to dryness
  11. customThe residue was then purified by mass

Sources & evidence

ORD record
ord-cdc3ccadcfde4454a3817b1bdb8f204d
Source dataset
uspto-grants-2015_06
Patent number
US09056859B2

Reaction notes

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