Allyl bromide → 3-(alpha-((2S,5S)-2,5-Dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N,N-diethylbenzamide

HRID 741633

반응식

HRID 741633 반응식
[Si]([O:8][C:9]1[CH:10]=[C:11]([CH:27]=[CH:28][CH:29]=1)[CH:12]([C:14]1[CH:15]=[C:16]([CH:24]=[CH:25][CH:26]=1)[C:17]([N:19]([CH2:22][CH3:23])[CH2:20][CH3:21])=[O:18])Cl)(C(C)(C)C)(C)C.[CH3:30][C@H:31]1[CH2:36][NH:35][C@@H:34]([CH3:37])[CH2:33][NH:32]1.C(Br)C=C.C(N(CC)C(=O)C1C=CC=CC=1)C>>[CH3:30][C@H:31]1[CH2:36][NH:35][C@@H:34]([CH3:37])[CH2:33][N:32]1[CH:12]([C:14]1[CH:15]=[C:16]([CH:24]=[CH:25][CH:26]=1)[C:17]([N:19]([CH2:20][CH3:21])[CH2:22][CH3:23])=[O:18])[C:11]1[CH:27]=[CH:28][CH:29]=[C:9]([OH:8])[CH:10]=1

참가 물질

5

반응물 4

HCID 7841Allyl bromideHCID 15542N,N-DiethylbenzamideHCID 61380(2S,5S)-2,5-dimethylpiperazineHCID 214803913-(3-((tert-butyldimethyl-silyl)oxy)-alpha-chlorobenzyl)-N,N-diethylbenzamide

생성물 1

HCID 677290583-(alpha-((2S,5S)-2,5-Dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N,N-diethylbenzamide

실험 절차

3-(α-((2S,5S)-2,5-Dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N,N-diethylbenzamide was prepared as a mixture of epimers from 3-(3-((tert-butyldimethylsilyl)oxy)-α-chlorobenzyl)-N,N-diethylbenzamide (Example 1, infra) and (+)-(2S,5S)-2,5-dimethylpiperazine [prepared from L-Ala-L-Ala-diketopiperazine (Bachem Chemicals, Philadelphia, Pa.) as described by Jung and Rohloff (J. Org. Chem. 50, 4909-13 (1985))] according to the methods of Example 1. This material was then alkylated with allyl bromide by methods similar to that in Example 4 to give a mixture of diastereomers that was separated by chromatography on silica gel (Waters Prep 500A, 0.1% triethylamine in dichloromethane). The first isomer to elute was deprotected by the method in Example 4 to give 3-((αR or αS)-α-((2S,5S)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N,N-diethylbenzamide. NMR (DMSO-d6, 200 MHz): δ0.890 (d, J=5.6 Hz, 3H); 0.981 (d, J=6.4 Hz, 3H); 1.00-1.25 (m, 6H); 2.10-2.48 (m, 4H); 2.59 (d, J=11.1 Hz, 1H); 2.73 (dd, J1 =7.8 Hz, J2 =14.1 Hz, 1H); 2.90-3.60 (m, 6H); 4.54 (s, 1H); 5.13 (d, J=9.0 Hz, 1H); 5.19 (d, J=16.2 Hz, 1H); 5.84 (m, 1H); 6.58 (d, J=8.0 Hz, 1H); 6.86 (s, 1H); 6.88 (d, J=7.1 Hz, 1H); 7.08 (t, J=7.6 Hz, 1H); 7.14 (d, J=7.8 Hz, 1H); 7.34 (t, J=7.6 Hz, 1H); 7.43 (s, 1H); 7.48 (d, J=7.7 Hz, 1H); 9.32 (s, 1H).

후처리

  1. customto give
  2. additiona mixture of diastereomers that
  3. customwas separated by chromatography on silica gel (Waters Prep 500A, 0.1% triethylamine in dichloromethane)
  4. washThe first isomer to elute
  5. customto give 3-((αR

출처 및 근거

ORD 기록
ord-c3e933aef4f04460995845c838ae11a1
출처 데이터셋
uspto-grants-1996_09
특허 번호
US05552404

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