1,2-Dichloroethane → (S)-4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-N-(1-(3-chlorophenyl)-2-(N-methyl-2-nitrophenylsulfonamido)ethyl)-2-fluorobenzamide

HRID 595963Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 595963
[NH2:1][C:2]1[C:3]([C:14]2[CH:22]=[CH:21][C:17]([C:18]([OH:20])=O)=[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.C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl.[NH2:38][C@@H:39]([C:55]1[CH:60]=[CH:59][CH:58]=[C:57]([Cl:61])[CH:56]=1)[CH2:40][N:41]([CH3:54])[S:42]([C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=1[N+:51]([O-:53])=[O:52])(=[O:44])=[O:43]>CN(C=O)C.CCOC(C)=O>[NH2:1][C:2]1[C:3]([C:14]2[CH:22]=[CH:21][C:17]([C:18]([NH:38][C@@H:39]([C:55]3[CH:60]=[CH:59][CH:58]=[C:57]([Cl:61])[CH:56]=3)[CH2:40][N:41]([CH3:54])[S:42]([C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=3[N+:51]([O-:53])=[O:52])(=[O:43])=[O:44])=[O:20])=[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

7

Edukt 4

HCID 111,2-DichloroethaneHCID 181649HOAtHCID 1180447134-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-2-fluorobenzoic acidHCID 118045765(S)-N-(2-amino-2-(3-chlorophenyl)ethyl)-N-methyl-2-nitrobenzenesulfonamide

Produkt 1

HCID 118045707(S)-4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-N-(1-(3-chlorophenyl)-2-(N-methyl-2-nitrophenylsulfonamido)ethyl)-2-fluorobenzamideAusbeute 82,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a solution of 4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-2-fluorobenzoic acid (1.55 g, 4.88 mmol) in DMF (16.28 mL) was added HOAt (0.997 g, 7.33 mmol), EDC (1.498 g, 7.82 mmol) DIEA (2.61 m l, 14.65 mmol) and (S)—N-(2-amino-2-(3-chlorophenyl)ethyl)-N-methyl-2-nitrobenzenesulfonamide (2.084 g, 5.13 mmol). The reaction mixture was stirred at room temperature for 3 h, and LCMS indicated the reaction was completed. The reaction mixture was diluted with EtOAc, and the organic was washed by sat.Na2CO3, water and brine, dried over Na2SO4, filtered off, and concentrated. The crude material was purified by flash chromatography eluting with 50% DCM/EtOAc (10% methanol) to provide (S)-4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-N-(1-(3-chlorophenyl)-2-(N-methyl-2-nitrophenylsulfonamido)ethyl)-2-fluorobenzamide (2.68 g, 4.01 mmol, 82%). LCMS: 669.1 (MH+), 0.95 min.

Aufarbeitung

  1. washthe organic was washed
  2. dry with materialNa2CO3, water and brine, dried over Na2SO4
  3. filtrationfiltered off
  4. concentrationconcentrated
  5. customThe crude material was purified by flash chromatography
  6. washeluting with 50% DCM/EtOAc (10% methanol)

Quellen und Nachweise

ORD-Eintrag
ord-2a1575761507484b800cbbf190d66cdb
Quelldatensatz
uspto-grants-2016_01
Patentnummer
US09242996B2

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