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

HRID 1744070노트

반응식

HRID 1744070 반응식
[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]

참가 물질

7

반응물 2

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

생성물 1

HCID 10273670N-(cyanomethyl)-4-methyl-2-{[4'-(1-piperazinyl)[1,1'-biphenyl]-4-yl]methoxy}pentanamide수율 87.2%

시약·촉매·용매 4

HCID 3283Diethyl Ether용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매HCID 516892Sodium Bicarbonate용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-4c5a7c5122964d6f9a099da2a52d4dc7
출처 데이터셋
uspto-grants-2006_03
특허 번호
US07012075B2

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