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4-Chlorophenylboronic acid → 18-[4-(4'-Chloro-4-methoxybiphenyl-2-ylmethoxy)phenyl]-17-cyclohexyl-1,4,11-triazatricyclo[11.5.2.016,19]icosa-13(20),14,16(19),17-tetraene-3,12-dione

HRID 39044
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 39044
C([O-])(O)=O.[Na+].Br[C:7]1[CH:48]=[CH:47][C:46]([O:49][CH3:50])=[CH:45][C:8]=1[CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[N:34]3[C:35]4[CH:36]=[C:22]([C:23](=[O:38])[NH:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][NH:31][C:32](=[O:37])[CH2:33]3)[CH:21]=[CH:20][C:19]=4[C:18]=2[CH:39]2[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40]2)=[CH:13][CH:12]=1.[Cl:51][C:52]1[CH:57]=[CH:56][C:55](B(O)O)=[CH:54][CH:53]=1>C(COC)OC.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[Cl:51][C:52]1[CH:57]=[CH:56][C:55]([C:7]2[CH:48]=[CH:47][C:46]([O:49][CH3:50])=[CH:45][C:8]=2[CH2:9][O:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3[N:34]4[C:35]5[CH:36]=[C:22]([C:23](=[O:38])[NH:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][NH:31][C:32](=[O:37])[CH2:33]4)[CH:21]=[CH:20][C:19]=5[C:18]=3[CH:39]3[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40]3)=[CH:13][CH:12]=2)=[CH:54][CH:53]=1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

6

Edukt 3

HCID 742994-Chlorophenylboronic acidHCID 516892Sodium BicarbonateHCID 4412925918-[4-(2-Bromo-5-methoxybenzyloxy)phenyl]-17-cyclohexyl-1,4,11-triaza-tricyclo[11.5.2.016,19]icosa-13(20),14,16(19),17-tetraene-3,12-dione

Produkt 1

HCID 5954908518-[4-(4'-Chloro-4-methoxybiphenyl-2-ylmethoxy)phenyl]-17-cyclohexyl-1,4,11-triazatricyclo[11.5.2.016,19]icosa-13(20),14,16(19),17-tetraene-3,12-dione

Reagenzien, Katalysatoren, Lösungsmittel

2
HCID 6102075Dichlorobis(triphenylphosphine)palladiumKatalysatorHCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
73 °C

Versuchsvorschrift

A saturated solution of NaHCO3 (1 mL) was added to a solution of 9 (20 mg, 0.029 mmol), 4-chlorobenzeneboronic acid (11 mg, 0.068 mmol) and bis(triphenyl-phosphine)palladium (II) chloride (4 mg, 0.0063 mmol) in dimethoxyethane (DME; 6 mL). The resulting solution was heated at 73° C. for 8 h. Then, the reaction mixture was successively cooled down to room temperature, partitioned between water and ethyl acetate, dried (Na2SO4) and evaporated. Purification by column chromatography (CH2Cl2/methanol, 97:3) afforded the target product contaminated with impurities. The product was further purified by trituration in methanol, then filtered off to give the target product 10: m/z=704 (M+H)+. NMR (DMSO-d6): δ (ppm) 1.23-1.33 (m, 6H), 1.42-1.53 (m, 8H), 1.67-1.77 (m, 2H), 1.87-2.02 (m, 2H), 2.80 (m, 1H, CH cyclohexyl), 3.15 (m, 4H, 2×CH2NHCO), 3.83 (s, 3H, OCH3), 4.44 (s, 2H, CH2CONH), 5.00 (s, 2H, CH2O), 7.04-7.09 (m, 3H), 7.23 (d, J=2.6 Hz, 1H), 7.29 (d, J=8.5 Hz, 1H), 7.40-7.47 (m, 7H), 7.76 (d, J=8.4 Hz, 1H), 7.93 (s, 1H), 8.30 (broad s, 1H, NH), 8.51 (broad s, 1H, NH).

Aufarbeitung

  1. temperatureThen, the reaction mixture was successively cooled down to room temperature
  2. custompartitioned between water and ethyl acetate
  3. dry with materialdried (Na2SO4)
  4. customevaporated
  5. customPurification by column chromatography (CH2Cl2/methanol, 97:3)
  6. customafforded the target product
  7. customThe product was further purified by trituration in methanol
  8. filtrationfiltered off

Quellen und Nachweise

ORD-Eintrag
ord-e104582997ac4515bc160e1926a37f5f
Quelldatensatz
uspto-grants-2013_09
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08524716B2

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