1,8-Diazabicyclo(5.4.0)undec-7-ene → Methyl 15-(((benzyloxy)carbonyl)amino)-12-isobutyl-6,11,14-trioxo-1,5,10,13,18,19-hexaazabicyclo[15.2.1]icosa-17(20),18-diene-9-carboxylate

HRID 627584ノート

反応式

HRID 627584 の反応式
[N:1]([CH2:4][CH2:5][CH2:6][NH:7][C:8](=[O:42])[CH2:9][CH2:10][CH:11]([C:38]([O:40][CH3:41])=[O:39])[NH:12][C:13](=[O:37])[CH:14]([CH2:33][CH:34]([CH3:36])[CH3:35])[NH:15][C:16](=[O:32])[CH:17]([CH2:29][C:30]#[CH:31])[NH:18][C:19](=[O:28])[O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[N+:2]=[N-:3].C1CCN2C(=NCCC2)CC1>C(Cl)Cl>[CH2:21]([O:20][C:19]([NH:18][CH:17]1[CH2:29][C:30]2=[CH:31][N:1]([N:2]=[N:3]2)[CH2:4][CH2:5][CH2:6][NH:7][C:8](=[O:42])[CH2:9][CH2:10][CH:11]([C:38]([O:40][CH3:41])=[O:39])[NH:12][C:13](=[O:37])[CH:14]([CH2:33][CH:34]([CH3:35])[CH3:36])[NH:15][C:16]1=[O:32])=[O:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

参加物

4

反応物 2

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 78148732Methyl 11-(3((3-azidopropyl)amino)-3-oxopropyl)-8-isobutyl-3,6,9-trioxo-1-phenyl-5-(prop-2-yn-1-yl)-2-oxa-4,7,10-triazadodecan-12-oate

生成物 1

HCID 78148733Methyl 15-(((benzyloxy)carbonyl)amino)-12-isobutyl-6,11,14-trioxo-1,5,10,13,18,19-hexaazabicyclo[15.2.1]icosa-17(20),18-diene-9-carboxylate収率 46.7%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of compound 10 (0.3 g: 0.512 mmol) in dry DCM (420 mL) under N2 atmosphere, was added DBU (0.233 g; 1.53 mmol) at room temperature with vigorous stirring. After 15 min, Cu(I)Br (0.073 g; 0.512 mmol) was added and the reaction mixture was stirred for 12 h at room temperature. The reaction mixture was quenched by adding 3M HCl (100 mL) and the aqueous layer was separated and extracted with DCM (2×500 mL). The combined organic layers were washed with brine (300 mL), and dried over anhydrous sodium sulfate. The solution was filtered and concentrated to give a crude product which was purified using flash chromatography (silica gel; methylene chloride/methanol 99:1) to give compound 11 as a white solid (0.14 g; 45% yield). 1H NMR (DMSO-d6) δ 8.5 (s, 1H), 8.1 (s, 1H), 7.5 (s, 1H), 7.3 (m, 5H), 5.0 (m, 2H), 4.3 (m, 1H), 4.1 (m, 2H), 3.6 (m, 2H), 3.3 (s, 3H), 3.11 (m, 2H), 2.88 (m, 2H), 2.98-2.24 (m, 5H), 1.49-1.8 (m, 5H), 0.86 (m, 6H).

後処理

  1. customThe reaction mixture was quenched
  2. additionby adding 3M HCl (100 mL)
  3. customthe aqueous layer was separated
  4. extractionextracted with DCM (2×500 mL)
  5. washThe combined organic layers were washed with brine (300 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationThe solution was filtered
  8. concentrationconcentrated
  9. customto give a crude product which
  10. customwas purified

出典と根拠

ORDレコード
ord-0fe814320a614bcf9b52c3ed65ff40f1
出典データセット
uspto-grants-2016_04
特許番号
US09309284B2

反応ノート

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