1,2-Dichloroethane → N-[(1R)-1-(5-bromopyridin-2-yl)ethyl]-2-[4-(5-methylisoxazol-4-yl)phenyl]acetamide

HRID 2383514

Reaktionsgleichung

Reaktionsgleichung von HRID 2383514
[CH3:1][C:2]1[O:6][N:5]=[CH:4][C:3]=1[C:7]1[CH:12]=[CH:11][C:10]([CH2:13][C:14]([OH:16])=O)=[CH:9][CH:8]=1.Cl.[Br:18][C:19]1[CH:20]=[CH:21][C:22]([C@H:25]([NH2:27])[CH3:26])=[N:23][CH:24]=1.C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C>CN(C=O)C.C(Cl)Cl>[Br:18][C:19]1[CH:20]=[CH:21][C:22]([C@H:25]([NH:27][C:14](=[O:16])[CH2:13][C:10]2[CH:9]=[CH:8][C:7]([C:3]3[CH:4]=[N:5][O:6][C:2]=3[CH3:1])=[CH:12][CH:11]=2)[CH3:26])=[N:23][CH:24]=1

Komponenten

8

Edukt 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 50999177(R)-1-(5-Bromopyridin-2-yl)ethanamine hydrochlorideHCID 66893040[4-(5-Methylisoxazol-4-yl)phenyl]acetic acid

Produkt 1

HCID 24765670N-[(1R)-1-(5-bromopyridin-2-yl)ethyl]-2-[4-(5-methylisoxazol-4-yl)phenyl]acetamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of 0.20 g (0.921 mmol) [4-(5-methylisoxazol-4-yl)phenyl]acetic acid in 2.00 ml DMF was added 0.22 g (0.92 mmol) (1R)-1-(5-bromopyridin-2-yl)ethanamine hydrochloride salt, 0.16 g (1.20 mmol) HOAT, 0.23 g (1.20 mmol) EDC, and 0.48 mL (2.76 mmol) DIEA. After 1.5 h at room temperature, the reaction mixture was diluted with CH2Cl2, washed three times with water, and washed with brine. The organic layer was dried over NaSO4, filtered and concentrated in vacuo. Purification by flash chromatography (1×14 cm silica gel, linear gradient 38-85% EtOAc:hexane) afforded N-[(1R)-1-(5-bromopyridin-2-yl)ethyl]-2-[4-(5-methylisoxazol-4-yl)phenyl]acetamide. 1H NMR (CDCl3, 400 MHz) 8.53 (d, 1H, J=2.11 Hz); 8.35 (s, 1H); 7.76 (dd, 1H, J=2.38 Hz, 8.33 Hz); 7.35 (s, 4H); 7.13 (d, 1H, J=8.24 Hz); 6.73 (br d, 1H, J=6.32 Hz); 5.11 (m, 1H); 3.61 (s, 2H); 2.58 (s, 3H); 1.42 (d, 3H, J=6.87). Electrospray mass spec M+H=402.0.

Aufarbeitung

  1. washwashed three times with water
  2. washwashed with brine
  3. dry with materialThe organic layer was dried over NaSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by flash chromatography (1×14 cm silica gel, linear gradient 38-85% EtOAc:hexane)

Quellen und Nachweise

ORD-Eintrag
ord-df17af0a0a634d0887d0f546ab50161e
Quelldatensatz
uspto-grants-2012_09
Patentnummer
US08263627B2

Verknüpfte Notizen

Wird geladen…