تفاعل #2446077

ord-67f7aa3c467c4447816dbb3322fc9ff2

معادلة التفاعل

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
المردود 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
المردود 75.0%

المتفاعلات

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

الكواشف

CN(C)c1ccncc1
DMAP

المذيبات

ClCCl
dichloromethane

ظروف التفاعل

درجة الحرارة
0°CELSIUS
الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    workup.ADDITIONwas added
  2. 2
    درجة الحرارةThe reaction mixture was warmed to 23° C.
  3. 3
    أخرىPurification via preparative HPLC
  4. 4
    أخرىfollowed by removal of the water via lyophilization

الإجراء التجريبي

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).

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US08685383B2uspto-grants-2014_04