Ammonium Chloride → 2-(2-(8-(hydroxymethyl)-1-isopropyl-7-(methylsulfonyl)-3,4-dihydropyrazino[1,2-a]indol-2(1H)-yl)-4-(trifluoromethyl)pyrimidin-5-yl)propan-2-ol

HRID 1483014Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1483014
C([O:4][CH2:5][C:6]1[C:14]([S:15]([CH3:18])(=[O:17])=[O:16])=[CH:13][C:12]2[N:11]3[CH2:19][CH2:20][N:21]([C:26]4[N:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[C:29]([C:36](=[O:38])[CH3:37])=[CH:28][N:27]=4)[CH:22]([CH:23]([CH3:25])[CH3:24])[C:10]3=[CH:9][C:8]=2[CH:7]=1)(=O)C.[Li+].[Cl-].[CH2:41]1COCC1.C[Mg]Cl.[NH4+].[Cl-]>C1COCC1.O>[OH:4][CH2:5][C:6]1[C:14]([S:15]([CH3:18])(=[O:17])=[O:16])=[CH:13][C:12]2[N:11]3[CH2:19][CH2:20][N:21]([C:26]4[N:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[C:29]([C:36]([OH:38])([CH3:41])[CH3:37])=[CH:28][N:27]=4)[CH:22]([CH:23]([CH3:25])[CH3:24])[C:10]3=[CH:9][C:8]=2[CH:7]=1

Komponenten

7

Edukt 4

HCID 25517Ammonium ChlorideHCID 68902752LiCl THFHCID 89815968(2-(5-Acetyl-4-(trifluoromethyl)pyrimidin-2-yl)-1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydropyrazino[1,2-a]indol-8-yl)methyl acetateHCID 178418332HCID 178418332, Verbindung

Produkt 1

HCID 717372752-(2-(8-(hydroxymethyl)-1-isopropyl-7-(methylsulfonyl)-3,4-dihydropyrazino[1,2-a]indol-2(1H)-yl)-4-(trifluoromethyl)pyrimidin-5-yl)propan-2-ol

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To a solution of (2-(5-acetyl-4-(trifluoromethyl)pyrimidin-2-yl)-1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydropyrazino[1,2-a]indol-8-yl)methyl acetate (37 mg, 67 μmol) in dry THF (2 mL) was added LaCl3.2 LiCl THF solution (0.12 mL, 70 μmol). The resulting mixture was stirred for 20 min at rt. The reaction mixture was cooled down to 0° C., MeMgCl in THF solution (3.0 M, 0.15 mL) was added slowly and the reaction mixture was allowed to stir at the same temperature for 0.5 h. Sat. aq. NH4Cl (1 mL) and water (2 mL) were added. The aqueous layer was extracted with EtOAc (4×10 mL). Combined organic phases were dried (Na2SO4) and concentrated. The crude residue was purified by silica chromatography and SFC separation to give isomers of 2-(2-(8-(hydroxymethyl)-1-isopropyl-7-(methylsulfonyl)-3,4-dihydropyrazino[1,2-a]indol-2(1H)-yl)-4-(trifluoromethyl)pyrimidin-5-yl)propan-2-ol.

Aufarbeitung

  1. temperatureThe reaction mixture was cooled down to 0° C.
  2. stirringto stir at the same temperature for 0.5 h
  3. extractionThe aqueous layer was extracted with EtOAc (4×10 mL)
  4. dry with materialCombined organic phases were dried (Na2SO4)
  5. concentrationconcentrated
  6. customThe crude residue was purified by silica chromatography and SFC separation

Quellen und Nachweise

ORD-Eintrag
ord-f5fab88904bf47fb897edc8877af92fd
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09416135B2

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