Ethanol → (2R,4R)-5-(3'-Chlorobiphenyl-4-yl)-2-hydroxy-4-[(3-hydroxy-3H-benzotriazole-5-carbonyl)amino]pentanoic Acid

HRID 516444Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 516444
[OH:1][N:2]1[C:6]2[CH:7]=[C:8]([C:11]([OH:13])=O)[CH:9]=[CH:10][C:5]=2[N:4]=[N:3]1.CN(C(ON1N=N[C:24]2[CH:25]=[CH:26][C:27](=[CH:29][C:23]1=2)[Cl:28])=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.C([O:50][C:51](=[O:65])[C@H:52]([OH:64])[CH2:53][C@H:54]([NH2:63])[CH2:55][C:56]1[CH:61]=[CH:60][C:59](Br)=[CH:58][CH:57]=1)C.ClC1C=C(B(O)O)C=CC=1.C([O-])([O-])=O.[K+].[K+].CCO.O.[Li+].[OH-]>CN(C=O)C.[Pd]>[Cl:28][C:27]1[CH:29]=[C:23]([C:59]2[CH:58]=[CH:57][C:56]([CH2:55][C@@H:54]([NH:63][C:11]([C:8]3[CH:9]=[CH:10][C:5]4[N:4]=[N:3][N:2]([OH:1])[C:6]=4[CH:7]=3)=[O:13])[CH2:53][C@@H:52]([OH:64])[C:51]([OH:65])=[O:50])=[CH:61][CH:60]=2)[CH:24]=[CH:25][CH:26]=1

Komponenten

12

Edukt 9

HCID 702EthanolHCID 962Water2×HCID 3939Lithium HydroxideHCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 24237871-hydroxy-1H-1,2,3-benzotriazole-6-carboxylic acidHCID 2734323(3-Chlorophenyl)boronic acidHCID 42624899O-(6-Chlorobenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphateHCID 67969401(2R,4R)-4-amino-5-(4-bromophenyl)-2-hydroxypentanoic acid ethyl ester

Produkt 1

HCID 67970017(2R,4R)-5-(3'-Chlorobiphenyl-4-yl)-2-hydroxy-4-[(3-hydroxy-3H-benzotriazole-5-carbonyl)amino]pentanoic AcidAusbeute 21 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 23938PalladiumKatalysatorHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

1-Hydroxy-1H-1,2,3-benzotriazole-6-carboxylic acid (56.6 mg, 316 μmol) and HCTU (131 mg, 316 μmol) were combined in DMF, and stirred for 5 minutes at room temperature. DIPEA (83 μL, 474 μmol) and (2R,4R)-4-amino-5-(4-bromophenyl)-2-hydroxypentanoic acid ethyl ester (50 mg, 0.2 mmol) were added, and the resulting mixture was stirred for 10 minutes. The mixture was evaporated under reduced pressure and purified (C18 column. 20-70% MeCN in water with 5% TFA). The clean fractions were lyophilized (40 mg). These solids were then combined with 3-chlorophenylboronic acid (44.5 mg, 285 μmol), K2CO3 (66 mg, 474 μmol), EtOH (0.8 mL, 10 mmol), and water (0.2 mL, 10 mmol). SilicaCat®DPP-Pd (0.28 mmol/g loading; 57 mg, 16 μmol) was added, and the resulting mixture was microwaved at 100° C. for 10 minutes. The mixture was filtered and 1 M LiOH in water (1.3 mL, 1.3 mmol) was added. The mixture was stirred for 30 minutes, evaporated under reduced pressure, and purified by preparative HPLC to yield the title compound (20.2 mg, purity 95%). MS m/z [M+H]+ calc'd for C24H21ClN4O5, 481.12. found 481.2.

Aufarbeitung

  1. stirringthe resulting mixture was stirred for 10 minutes
  2. customThe mixture was evaporated under reduced pressure
  3. custompurified (C18 column. 20-70% MeCN in water with 5% TFA)
  4. customthe resulting mixture was microwaved at 100° C. for 10 minutes
  5. filtrationThe mixture was filtered
  6. stirringThe mixture was stirred for 30 minutes
  7. customevaporated under reduced pressure
  8. custompurified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-66ea124e8250420cbb1f2782c6b3e288
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09108934B2

Notizen zur Reaktion

Wird geladen…