Triethylamine → 5-amino-N-(4-((1R,3S)-3-aminocyclohexyl)pyridin-3-yl)-3,3'-difluoro-2,4'-bipyridine-6-carboxamide

HRID 1523536Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1523536
[NH2:1][C:2]1[C:3]([C:10]([NH:12][C:13]2[CH:14]=[N:15][CH:16]=[CH:17][C:18]=2[C@@H:19]2[CH2:24][CH2:23][CH2:22][C@H:21]([N:25]3C(=O)C4C(=CC=CC=4)C3=O)[CH2:20]2)=[O:11])=[N:4][C:5](Br)=[C:6]([F:8])[CH:7]=1.[F:36][C:37]1[CH:38]=[N:39][CH:40]=[CH:41][C:42]=1B(O)O.C(N(CC)CC)C>CCO.C1(C)C=CC=CC=1>[NH2:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([C:42]2[CH:41]=[CH:40][N:39]=[CH:38][C:37]=2[F:36])=[N:4][C:3]=1[C:10]([NH:12][C:13]1[CH:14]=[N:15][CH:16]=[CH:17][C:18]=1[C@@H:19]1[CH2:24][CH2:23][CH2:22][C@H:21]([NH2:25])[CH2:20]1)=[O:11]

Komponenten

5

Edukt 3

HCID 8471TriethylamineHCID 27793533-Fluoropyridine-4-boronic acidHCID 86639734HCID 86639734, Verbindung

Produkt 1

HCID 461787745-amino-N-(4-((1R,3S)-3-aminocyclohexyl)pyridin-3-yl)-3,3'-difluoro-2,4'-bipyridine-6-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 21863594Toluene ethanolLösungsmittel

Versuchsvorschrift

A solution of 3-amino-6-bromo-N-(4-((1R,3S)-3-(1,3-dioxoisoindolin-2-yl)cyclohexyl)pyridin-3-yl)-5-fluoropicolinamide (1.0 equiv), 3-fluoropyridin-4-yl-boronic acid (3.0 equiv.), tetrakistriphenylphosphine (0.2 equiv.) and triethylamine (3.0 equiv.) in 1:1 EtOH/toluene (0.1 M) was heated at 120° C. with microwave irradiation for 1200 seconds. Upon cooling, removal of the volatiles in vacuo, the Suzuki product was directly purified by reverse phase HPLC. The product fraction was lyophilized and the resulting phthalimide group was deprotected as described in Method 9 yielding, after RP HPLC purification and lyophilization, 5-amino-N-(4-((1R,3S)-3-aminocyclohexyl)-pyridin-3-yl)-3,3′-difluoro-2,4′-bipyridine-6-carboxamide as the TFA salt. LCMS (m/z): 425.1 (MH+); LC Rt=2.08 min.

Aufarbeitung

  1. temperatureUpon cooling
  2. customremoval of the volatiles in vacuo
  3. customthe Suzuki product was directly purified by reverse phase HPLC
  4. customafter RP HPLC purification and lyophilization, 5-amino-N-(4-((1R,3S)-3-aminocyclohexyl)-pyridin-3-yl)-3,3′-difluoro-2,4′-bipyridine-6-carboxamide as the TFA salt

Quellen und Nachweise

ORD-Eintrag
ord-0aff9261d2384201af8c8b3a430cc422
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09079889B2

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