Diisopropylethylamine → 3-{[[4-(BOC-methyl-amino)-cyclohexyl]-(3-chloro-4,7-difluoro-benzo[b]thiophene-2-carbonyl)-amino]-methyl}-4-methoxy-benzene boronic acid

HRID 2389566Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2389566
[C:1]([N:8]([CH3:28])[CH:9]1[CH2:14][CH2:13][CH:12]([NH:15][CH2:16][C:17]2[CH:18]=[C:19]([B:25]([OH:27])[OH:26])[CH:20]=[CH:21][C:22]=2[O:23][CH3:24])[CH2:11][CH2:10]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CCN(C(C)C)C(C)C.[Cl:38][C:39]1[C:40]2[C:50]([F:51])=[CH:49][CH:48]=[C:47]([F:52])[C:41]=2[S:42][C:43]=1[C:44](Cl)=[O:45]>C(Cl)Cl>[C:1]([N:8]([CH3:28])[CH:9]1[CH2:10][CH2:11][CH:12]([N:15]([CH2:16][C:17]2[CH:18]=[C:19]([B:25]([OH:26])[OH:27])[CH:20]=[CH:21][C:22]=2[O:23][CH3:24])[C:44]([C:43]2[S:42][C:41]3[C:47]([F:52])=[CH:48][CH:49]=[C:50]([F:51])[C:40]=3[C:39]=2[Cl:38])=[O:45])[CH2:13][CH2:14]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Komponenten

5

Edukt 3

HCID 81531DiisopropylethylamineHCID 219384153-Chloro-4,7-difluorobenzo[b]thiophene-2-carbonyl chlorideHCID 252081913-{[4-(BOC-methyl-amino)-cyclohexylamino]-methyl}-4-methoxy-benzene boronic acid

Produkt 1

HCID 596835093-{[[4-(BOC-methyl-amino)-cyclohexyl]-(3-chloro-4,7-difluoro-benzo[b]thiophene-2-carbonyl)-amino]-methyl}-4-methoxy-benzene boronic acid

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A solution of boronic acid 4 (7.60 g, 19.4 mmol) in DCM (300 mL) at 0° C. is treated with DIPEA (7.40 mL, 42.7 mmol), followed by acid chloride 8 (6.21 g, 23.3 mmol) in one portion. After warming to RT, the solution is stirred 3 h. Analysis by LC/MS at this juncture confirmed the reaction is complete. Thus the solvent is removed in vacuo and the residue purified by chromatography (gradient elution—60% EtOAc in heptane with 0.5% triethylamine increasing to neat EtOAc with 0.5% triethylamine, then 10-20% MeOH in EtOAc with 0.5% triethylamine) to afford the title compound.

Aufarbeitung

  1. customThus the solvent is removed in vacuo
  2. customthe residue purified by chromatography (
  3. washgradient elution—60% EtOAc in heptane with 0.5% triethylamine increasing to neat EtOAc with 0.5% triethylamine

Quellen und Nachweise

ORD-Eintrag
ord-b7cb475f19dd4d84b6430126b4280db4
Quelldatensatz
uspto-grants-2012_09
Patentnummer
US08273747B2

Notizen zur Reaktion

Wird geladen…