反応 #2446077

ord-67f7aa3c467c4447816dbb3322fc9ff2

反応方程式

C[C@H](NC(=O)OC(C)(C)C)C(=O)O
BOC-L-alanine
CC(C)N=C=NC(C)C
diisopropylcarbodiimide
CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@@H](Cc1ccccc1)C(=O)O)OC)N(C)C(=O)[C@@H](NC(=O)[C@H](C(C)C)N(C)C)C(C)C.[NH-]CCCO
auristatin F hydroxypropylamide
CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@@H](Cc1ccccc1)C(=O)O)OC)N(C)C(=O)[C@@H](NC(=O)[C@H](C(C)C)N(C)C)C(C)C.[NH-]CCCO
Auristatin F hydroxypropylamide
→
CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@@H](Cc1ccccc1)C(=O)O)OC)N(C)C(=O)[C@@H](NC(=O)[C@H](C(C)C)N(C)C)C(C)C.C[C@H](NC(=O)OC(C)(C)C)C(=O)O.[NH-]CCCO
title compound
収率 75.0%
CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@@H](Cc1ccccc1)C(=O)O)OC)N(C)C(=O)[C@@H](NC(=O)[C@H](C(C)C)N(C)C)C(C)C.C[C@H](NC(=O)OC(C)(C)C)C(=O)O.[NH-]CCCO
Auristatin F hydroxypropylamide Boc-L-Alanine
収率 75.0%

反応物

C[C@H](NC(=O)OC(C)(C)C)C(=O)O
BOC-L-alanine
CC(C)N=C=NC(C)C
diisopropylcarbodiimide
CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@@H](Cc1ccccc1)C(=O)O)OC)N(C)C(=O)[C@@H](NC(=O)[C@H](C(C)C)N(C)C)C(C)C.[NH-]CCCO
auristatin F hydroxypropylamide
CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@@H](Cc1ccccc1)C(=O)O)OC)N(C)C(=O)[C@@H](NC(=O)[C@H](C(C)C)N(C)C)C(C)C.[NH-]CCCO
Auristatin F hydroxypropylamide

試薬

CN(C)c1ccncc1
DMAP

溶媒

ClCCl
dichloromethane

反応条件

温度
0°CELSIUS
詳細条件
See reaction.notes.procedure_details.

後処理

  1. 1
    workup.ADDITIONwas added
  2. 2
    温度The reaction mixture was warmed to 23° C.
  3. 3
    その他Purification via preparative HPLC
  4. 4
    その他followed by removal of the water via lyophilization

実験手順

BOC-L-alanine (117.0 mg, 0.618 mmol) and DMAP (94.0 mg, 0.772 mmol) were taken up in dichloromethane and then diisopropylcarbodiimide (52.6 μL, 0.340 mmol) was added. The reaction mixture was cooled to 0° C. and stirred for 10 minutes after which auristatin F-hydroxypropylamide (124 mg, 0.154 mmol, prepared as described in Example 48) was added. The reaction mixture was warmed to 23° C. and stirred for 18 hours. Purification via preparative HPLC followed by removal of the water via lyophilization afforded the title compound as beige solid (112 mg, 75% yield).

出典

DOI: 10.6084/m9.figshare.5104873.v1特許: US08685383B2uspto-grants-2014_04