Triethylamine → N-(4-(3-amino-4-hydroxycyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide

HRID 1523535Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1523535
Br[C:2]1[N:7]=[C:6]([C:8]([NH:10][C:11]2[CH:12]=[N:13][CH:14]=[CH:15][C:16]=2[CH:17]2[CH2:33][CH:21]3[N:22](C(OC(C)(C)C)=O)C(=O)[O:24][CH:20]3[CH2:19][CH2:18]2)=[O:9])[CH:5]=[CH:4][C:3]=1[F:34].[F:35][C:36]1[CH:41]=[CH:40][CH:39]=[C:38]([F:42])[C:37]=1B(O)O.C(N(CC)CC)C>CCO.C1(C)C=CC=CC=1>[NH2:22][CH:21]1[CH:20]([OH:24])[CH2:19][CH2:18][CH:17]([C:16]2[CH:15]=[CH:14][N:13]=[CH:12][C:11]=2[NH:10][C:8](=[O:9])[C:6]2[CH:5]=[CH:4][C:3]([F:34])=[C:2]([C:37]3[C:36]([F:35])=[CH:41][CH:40]=[CH:39][C:38]=3[F:42])[N:7]=2)[CH2:33]1

Komponenten

5

Edukt 3

HCID 8471TriethylamineHCID 27343362,6-Difluorophenylboronic acidHCID 59226599tert-butyl 5-(3-(6-bromo-5-fluoropicolinamido)pyridin-4-yl)-2-oxohexahydrobenzo[d]oxazole-3(2H)-carboxylate

Produkt 1

HCID 59226417N-(4-(3-amino-4-hydroxycyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 21863594Toluene ethanolLösungsmittel

Versuchsvorschrift

A solution of tert-butyl 5-(3-(6-bromo-5-fluoropicolinamido)pyridin-4-yl)-2-oxohexahydrobenzo[d]oxazole-3(2H)-carboxylate (1.0 equiv), 2,6-difluorophenyl 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 cyclic carbamate and Boc groups were deprotected as described in Method 9 yielding, after RP HPLC purification and lyophilization, N-(4-(3-amino-4-hydroxycyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamideas the TFA salt. LCMS (m/z): 443.2 (MH+); LC Rt=2.11 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, N-(4-(3-amino-4-hydroxycyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamideas the TFA salt

Quellen und Nachweise

ORD-Eintrag
ord-b14a9e6709f9445a9a3f1fc81bb373ac
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09079889B2

Notizen zur Reaktion

Wird geladen…