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 1521547Notes

Reaction equation

HRID 1521547 reaction equation
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

Participants

7

Reactant 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, compound

Product 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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-9a43ed168dcd4b69b0832c1f13e1dee4
Source dataset
uspto-grants-2015_07
Patent number
US09073931B2

Reaction notes

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