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 1521547노트

반응식

HRID 1521547 반응식
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

참가 물질

7

반응물 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, 화합물

생성물 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

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매2회

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-9a43ed168dcd4b69b0832c1f13e1dee4
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09073931B2

반응 노트

불러오는 중…