Réaction #155366

ord-e1e02cc4069141228fd25e1f04d271b5

Équation de réaction

NCCCO
3-aminopropan-1-ol
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
Auristatin F
CN(C)C(On1nnc2cccnc21)=[N+](C)C.F[P-](F)(F)(F)(F)F
HATU
CCN(C(C)C)C(C)C
diisopropylethylamine
→
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
title compound
Rendement 68.0%
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.[NH-]CCCO
Auristatin F hydroxypropylamide
Rendement 68.0%

Réactifs

NCCCO
3-aminopropan-1-ol
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
Auristatin F
CN(C)C(On1nnc2cccnc21)=[N+](C)C.F[P-](F)(F)(F)(F)F
HATU
CCN(C(C)C)C(C)C
diisopropylethylamine

Réactifs

Aucun

Solvants

CN(C)C=O
DMF

Conditions de réaction

Température
23°CELSIUS
Conditions détaillées
See reaction.notes.procedure_details.

Traitement

  1. 1
    AutreReduction of the volume to 1.4 mL under high vacuum followed by purification via preparative HPLC (10-90 solvent B gradient over 20 minutes eluting with 0.1% TFA/Water, 0.1% TFA/CH3CN)

Mode opératoire

Auristatin F (150 mg, 0.201 mmol), HATU (153.0 mg, 0.402 mmol), and diisopropylethylamine (108 μL, 0.603 mmol) were taken up in DMF (5 mL) and 3-aminopropan-1-ol (45.9 μL, 0.603 mmol) was added. The mixture was stirred at 23° C. for 45 minutes at which time LCMS analysis showed complete disappearance of the starting material. Reduction of the volume to 1.4 mL under high vacuum followed by purification via preparative HPLC (10-90 solvent B gradient over 20 minutes eluting with 0.1% TFA/Water, 0.1% TFA/CH3CN) afforded the title compound as white solid (109 mg, 68% yield).

Source

DOI: 10.6084/m9.figshare.5104873.v1Brevet: US08821850B2uspto-grants-2014_09