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

HRID 1744070ノート

反応式

HRID 1744070 の反応式
[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]

参加物

7

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 4

HCID 3283Diethyl Ether溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒HCID 516892Sodium Bicarbonate溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-4c5a7c5122964d6f9a099da2a52d4dc7
出典データセット
uspto-grants-2006_03
特許番号
US07012075B2

反応ノート

読み込み中…