1,2-Dichloroethane → (S)-4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-N-(2-azido-1-(3-chloro-5-fluorophenyl)ethyl)-2-fluorobenzamide

HRID 596011Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 596011
[NH2:1][C:2]1[C:3]([C:14]2[CH:22]=[CH:21][C:17]([C:18](O)=[O:19])=[C:16]([F:23])[CH:15]=2)=[N:4][C:5]([CH:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[CH:6][N:7]=1.[N:24]([CH2:27][C@H:28]([C:30]1[CH:35]=[C:34]([F:36])[CH:33]=[C:32]([Cl:37])[CH:31]=1)[NH2:29])=[N+:25]=[N-:26].CCN(C(C)C)C(C)C.C(Cl)CCl>CN(C=O)C.CCOC(C)=O.O>[NH2:1][C:2]1[C:3]([C:14]2[CH:22]=[CH:21][C:17]([C:18]([NH:29][C@@H:28]([C:30]3[CH:35]=[C:34]([F:36])[CH:33]=[C:32]([Cl:37])[CH:31]=3)[CH2:27][N:24]=[N+:25]=[N-:26])=[O:19])=[C:16]([F:23])[CH:15]=2)=[N:4][C:5]([CH:8]2[CH2:9][CH2:10][O:11][CH2:12][CH2:13]2)=[CH:6][N:7]=1

Komponenten

8

Edukt 4

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 1180447134-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-2-fluorobenzoic acidHCID 118046055(S)-2-azido-1-(3-chloro-5-fluorophenyl)ethanamine

Produkt 1

HCID 118046045(S)-4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-N-(2-azido-1-(3-chloro-5-fluorophenyl)ethyl)-2-fluorobenzamideAusbeute 58 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a solution of 4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-2-fluorobenzoic acid (126 mg, 0.398 mmol) in DMF (1328 μl) was added (S)-2-azido-1-(3-chloro-5-fluorophenyl)ethanamine (100.0 mg, 0.398 mmol), DIEA (348 μl, 1.991 mmol), EDC (153 mg, 0.797 mmol), and aza-HOBt (81 mg, 0.597 mmol). The reaction mixture was stirred for 15 h. After water was added, the reaction mixture was worked up with EtOAc. The organic layer was dried over Na2SO4, filtered off, and concentrated in vacuo. The crude product was purified by flash chromatography (gradient EtOAc in heptane) to provide (S)-4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-N-(2-azido-1-(3-chloro-5-fluorophenyl)ethyl)-2-fluorobenzamide (118 mg, 58%). LCMS (m/z): 514.2 (MH+), 0.91 min.

Aufarbeitung

  1. dry with materialThe organic layer was dried over Na2SO4
  2. filtrationfiltered off
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by flash chromatography (gradient EtOAc in heptane)

Quellen und Nachweise

ORD-Eintrag
ord-55f3fedf4c7143c69d924429aeebafb1
Quelldatensatz
uspto-grants-2016_01
Patentnummer
US09242996B2

Notizen zur Reaktion

Wird geladen…