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 627584Notes

Reaction equation

HRID 627584 reaction equation
[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

Participants

4

Reactant 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

Product 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-carboxylateYield 46.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-0fe814320a614bcf9b52c3ed65ff40f1
Source dataset
uspto-grants-2016_04
Patent number
US09309284B2

Reaction notes

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