Methanesulfonic Acid → N-(cyanomethyl)-4-methyl-2-{[4'-(1-piperazinyl)[1,1'-biphenyl]-4-yl]methoxy}pentanamide

HRID 1744070Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1744070
[C:1]([CH2:3][NH:4][C:5]([CH:7]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[CH:25]=[CH:24][C:23]([N:26]3[CH2:31][CH2:30][N:29](C(OC(C)(C)C)=O)[CH2:28][CH2:27]3)=[CH:22][CH:21]=2)=[CH:16][CH:15]=1)[CH2:8][CH:9]([CH3:11])[CH3:10])=[O:6])#[N:2].CS(O)(=O)=O>O1CCCC1.C(OCC)C.C(OC(=O)C)C.C(=O)(O)[O-].[Na+]>[C:1]([CH2:3][NH:4][C:5](=[O:6])[CH:7]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[CH:25]=[CH:24][C:23]([N:26]3[CH2:27][CH2:28][NH:29][CH2:30][CH2:31]3)=[CH:22][CH:21]=2)=[CH:16][CH:15]=1)[CH2:8][CH:9]([CH3:11])[CH3:10])#[N:2]

Komponenten

7

Edukt 2

HCID 6395Methanesulfonic AcidHCID 22235855Tert-butyl 4-{4'-[(1-{[(cyanomethyl)amino]carbonyl}-3-methylbutoxy)methyl][1,1'-biphenyl]-4-yl}-1-piperazinecarboxylate

Produkt 1

HCID 10273670N-(cyanomethyl)-4-methyl-2-{[4'-(1-piperazinyl)[1,1'-biphenyl]-4-yl]methoxy}pentanamideAusbeute 87,2 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 3283Diethyl EtherLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 516892Sodium BicarbonateLösungsmittel

Versuchsvorschrift

A solution of tert-butyl 4-{4′-[(1-{[(cyanomethyl)amino]carbonyl}-3-methylbutoxy)methyl][1,1′-biphenyl]-4-yl}-1-piperazinecarboxylate (115 mg, 0.21 mmoles) in tetrahydrofuran (3.5 mL) was treated with methanesulfonic acid (30 μL, 0.4 mmoles). The same amount of acid was added 5 times at 1.5 hour intervals and stirred overnight. Acid addition was resumed and two more portions (30 μL, 0.4 mmoles) were added, with a 1.5 hour interval. The reaction was diluted with diethyl ether, ethylacetate, sat. aq. sodium bicarbonate. The phases were separated and the organic phase was dried over sodium sulfate and concentrated under reduced pressure. The product was chromatographed (1% sat. aq. ammonium hydroxyde, 9% methanol, 90% dichloromethane) to obtain 77 mg N-(cyanomethyl)-4-methyl-2-{[4′-(1-piperazinyl)[1,1′-biphenyl]-4-yl]methoxy}pentanamide, a yellowish solid.

Aufarbeitung

  1. additionThe same amount of acid was added 5 times at 1.5 hour intervals
  2. additionAcid addition
  3. additiontwo more portions (30 μL, 0.4 mmoles) were added, with a 1.5 hour interval
  4. customThe phases were separated
  5. dry with materialthe organic phase was dried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe product was chromatographed (1% sat. aq. ammonium hydroxyde, 9% methanol, 90% dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-4c5a7c5122964d6f9a099da2a52d4dc7
Quelldatensatz
uspto-grants-2006_03
Patentnummer
US07012075B2

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