1,2-Dichloroethane → 4-(2-Fluorophenyl)-1-(4-{(1s,5r)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}butyl)-2(1h)-pyrimidinone hydrochloride

HRID 1514451ノート

反応式

HRID 1514451 の反応式
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][N:11]([CH2:14][CH2:15][CH2:16][CH:17]=O)[C:10](=[O:19])[N:9]=1.[F:20][C:21]([F:35])([F:34])[C:22]1[CH:27]=[CH:26][C:25]([C@:28]23[CH2:33][C@H:32]2[CH2:31][NH:30][CH2:29]3)=[CH:24][CH:23]=1.CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[Cl:54]CCCl>>[ClH:54].[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][N:11]([CH2:14][CH2:15][CH2:16][CH2:17][N:30]2[CH2:31][C@H:32]3[C@:28]([C:25]4[CH:24]=[CH:23][C:22]([C:21]([F:20])([F:35])[F:34])=[CH:27][CH:26]=4)([CH2:33]3)[CH2:29]2)[C:10](=[O:19])[N:9]=1

参加物

6

反応物 5

HCID 111,2-DichloroethaneHCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 592428054-[4-(2-Fluoro-phenyl)-2-oxo-2H-pyrimidin-1-yl]-butyraldehydeHCID 59337591(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane

生成物 1

HCID 686995284-(2-Fluorophenyl)-1-(4-{(1s,5r)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}butyl)-2(1h)-pyrimidinone hydrochloride収率 58%

反応条件

温度
0 °C

実験手順

4-[4-(2-Fluoro-phenyl)-2-oxo-2H-pyrimidin-1-yl]-butyraldehyde (Prep41, 50 mg, 0.19 mmol) was dissolved in DCE (5.5 ml). The resulting solution was cooled at 0° C. and then (1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (Prep4, 53 mg, 0.23 mmol), AcOH (13 μl) and NaBH(AcO)3 (45 mg, 0.21 mmol) were added. The mixture was stirred for 10 minutes at 0° C. 1N NaOHaq was added and the product was extracted with DCM. The organic phase was dried (Na2SO4) and evaporated. The crude was purified by flash chromatography with DCM-MeOH—NH4OH (20-0.2-0.2) to give 52 mg of the title compound (58% yield) as a free base.

後処理

  1. addition1N NaOHaq was added
  2. extractionthe product was extracted with DCM
  3. dry with materialThe organic phase was dried (Na2SO4)
  4. customevaporated
  5. customThe crude was purified by flash chromatography with DCM-MeOH—NH4OH (20-0.2-0.2)

出典と根拠

ORDレコード
ord-9d8bbfb859294735a52ebe627231fddb
出典データセット
uspto-grants-2012_07
特許番号
US08222266B2

反応ノート

読み込み中…