Triethylamine → tert-Butyl 4-(4-((4-(2-(1-amino-1-oxobutan-2-yl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

HRID 592360Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 592360
[NH2:1][C:2](=[O:44])[CH:3]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[C:12]#[C:13][C:14]1[C:19]([C:20]([F:23])([F:22])[F:21])=[CH:18][N:17]=[C:16]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([CH:31]3[CH2:36][CH2:35][N:34]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:33][CH2:32]3)=[CH:27][CH:26]=2)[N:15]=1)[CH2:4][CH3:5].CCN(CC)CC>CN(C=O)C.CCOC(C)=O.[Pd]>[NH2:1][C:2](=[O:44])[CH:3]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[CH2:12][CH2:13][C:14]1[C:19]([C:20]([F:23])([F:22])[F:21])=[CH:18][N:17]=[C:16]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([CH:31]3[CH2:36][CH2:35][N:34]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:33][CH2:32]3)=[CH:27][CH:26]=2)[N:15]=1)[CH2:4][CH3:5]

Komponenten

6

Edukt 2

HCID 8471TriethylamineHCID 86712282tert-Butyl 4-(4-((4-((2-(1-amino-1-oxobutan-2-yl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

Produkt 1

HCID 86712283tert-Butyl 4-(4-((4-(2-(1-amino-1-oxobutan-2-yl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylateAusbeute 244,9 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 23938PalladiumKatalysatorHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A suspension of 10% Pd/C (100 mg), tert-butyl 4-(4-((4-((2-(1-amino-1-oxobutan-2-yl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (A1) (167 mg, 0.275 mmol) and Et3N (1.0 mL) in DMF (10 mL) was stirred under an atmosphere of hydrogen for 16 hours. The resulting mixture was diluted with EtOAc (60 mL), filtered through Celite then the solvent removed under reduced pressure to give the title compound A2 as a yellow oil (412 mg, 98%); 1H NMR (400 MHz, d6-DMSO) δ 10.15 (s, 1H), 8.67 (s, 1H), 7.67 (d, J=8.6 Hz, 2H), 7.49-7.42 (m, 1H), 7.31 (s, 1H), 7.22-7.14 (m, 5H), 6.87 (s, 1H), 4.06 (d, J=10.5 Hz, 2H), 3.61 (dd, J=8.8, 6.1 Hz, 1H), 3.29-2.94 (m, 4H), 2.88-2.74 (m, obscured by solvent), 2.70-2.59 (m, 1H), 2.04-1.92 (m, 1H), 1.74 (d, J=12.6 Hz, 2H), 1.61-1.43 (m, 3H), 1.41 (s, 9H), 0.83 (t, J=7.3 Hz, 3H). LCMS-A: rt 6.722 min; m/z 612 [M+H]+.

Aufarbeitung

  1. filtrationfiltered through Celite
  2. customthe solvent removed under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-1c20a54e7b404d848242abb06e1b7220
Quelldatensatz
uspto-grants-2016_01
Patentnummer
US09238644B2

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