Tetrabutylammonium Fluoride → N-(cyanomethyl)-4-methyl-2-{[4'-(1-piperazinyl)[1,1'-biphenyl]-3-yl]oxy}pentanamide

HRID 1744065Notes

Reaction equation

HRID 1744065 reaction equation
[C:1]([CH2:3][NH:4][C:5]([CH:7]([O:12][C:13]1[CH:14]=[C:15]([C:19]2[CH:24]=[CH:23][C:22]([N:25]3[CH2:30][CH2:29][N:28](C(O[Si](C(C)C)(C(C)C)C(C)C)=O)[CH2:27][CH2:26]3)=[CH:21][CH:20]=2)[CH:16]=[CH:17][CH:18]=1)[CH2:8][CH:9]([CH3:11])[CH3:10])=[O:6])#[N:2].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1.C(OCC)C.C(OCC)(=O)C.O.C(=O)(O)[O-].[Na+]>[C:1]([CH2:3][NH:4][C:5](=[O:6])[CH:7]([O:12][C:13]1[CH:14]=[C:15]([C:19]2[CH:20]=[CH:21][C:22]([N:25]3[CH2:26][CH2:27][NH:28][CH2:29][CH2:30]3)=[CH:23][CH:24]=2)[CH:16]=[CH:17][CH:18]=1)[CH2:8][CH:9]([CH3:11])[CH3:10])#[N:2]

Participants

8

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 10282346Triisopropylsilyl 4-[3'-(1-{[(cyanomethyl)amino]carbonyl}-3-methylbutoxy)[1,1'-biphenyl]-4-yl]-1-piperazinecarboxylate

Product 1

HCID 10272735N-(cyanomethyl)-4-methyl-2-{[4'-(1-piperazinyl)[1,1'-biphenyl]-3-yl]oxy}pentanamide

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

Triisopropylsilyl 4-[3′-(1-{[(cyanomethyl)amino]carbonyl}-3-methylbutoxy)[1,1′-biphenyl]-4-yl]-1-piperazinecarboxylate (365 mg, 0.6 mmoles) in 8 mL of tetrahydrofuran was treated with tetrabutylammonium fluoride (0.75 mL, 1 M in THF, 0.75 mmoles) at 0° C. until the disappearance of the starting material was observed by TLC. The reaction was diluted with diethyl ether, ethyl acetate, water and sat. aq. sodium bicarbonate. The phases were separated, the organic phase washed with brine and dried over sodium sulfate. After concentration under reduced pressure, the residue was purified by flash chromatography (1% sat. aqueous ammonium hydroxide, 9% methanol, 90% dichloromethane) to afford N-(cyanomethyl)-4-methyl-2-{[4′-(1-piperazinyl)[1,1′-biphenyl]-3-yl]oxy}pentanamide. MS (−ESI): 405.3 [M−1]−.

Workup

  1. customThe phases were separated
  2. washthe organic phase washed with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationAfter concentration under reduced pressure
  5. customthe residue was purified by flash chromatography (1% sat. aqueous ammonium hydroxide, 9% methanol, 90% dichloromethane)

Sources & evidence

ORD record
ord-2827916379644f8db9cb0d09958ef59a
Source dataset
uspto-grants-2006_03
Patent number
US07012075B2

Reaction notes

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