Sodium Hydroxide → 5-(6-chloro-3-pyridinyl)-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione

HRID 12801ノート

反応式

HRID 12801 の反応式
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[C:9](=[O:19])[NH:10][C:11](=[O:18])[N:12]([CH2:14][CH2:15][CH:16]=O)[CH:13]=2)=[CH:4][CH:3]=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.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[OH-].[Na+]>ClC(Cl)C.CO.[Cl-].[Na+].O.CC(O)=O>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[C:9](=[O:19])[NH:10][C:11](=[O:18])[N:12]([CH2:14][CH2:15][CH2:16][N:30]3[CH2:31][C@H:32]4[C@:28]([C:25]5[CH:24]=[CH:23][C:22]([C:21]([F:20])([F:35])[F:34])=[CH:27][CH:26]=5)([CH2:33]4)[CH2:29]3)[CH:13]=2)=[CH:4][CH:3]=1

参加物

8

反応物 4

HCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 589942093-[5-(6-Chloro-pyridin-3-yl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-propionaldehydeHCID 59337591(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane

生成物 1

HCID 247582225-(6-chloro-3-pyridinyl)-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione収率 34.8%

試薬・触媒・溶媒 3

HCID 176Acetic Acid溶媒HCID 22036585Dichloroethane methanol溶媒HCID 57417360Sodium chloride; water溶媒

反応条件

温度
0 °C

実験手順

A solution of 3-[5-(6-Chloro-pyridin-3-yl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-propionaldehyde (Prep93, 0.82 mmol), (1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (Prep4, 186 mg, 0.82 mmol), and AcOH (58 μl) in dichloroethane-MeOH (10-0.1, 8 ml) was cooled to 0° C. NaBH(AcO)3 (182 mg, 0.86 mmol) was added portionwise. The mixture was stirred at 0° C. for further one hour and then basified with 1N NaOH. Brine was added and the product extracted with DCM. The organic phase was dried (Na2SO4) and evaporated. The residue was redissolved in DCM and stirred overnight in the presence of PS-isocyanate. The mixture was filtered and the solvent evaporated. The crude was purified by flash chromatography eluting with DCM-MeOH—NH4OH (98:2:0.2) to give 140 mg of the title compound (34% yield).

後処理

  1. extractionthe product extracted with DCM
  2. dry with materialThe organic phase was dried (Na2SO4)
  3. customevaporated
  4. dissolutionThe residue was redissolved in DCM
  5. stirringstirred overnight in the presence of PS-isocyanate
  6. filtrationThe mixture was filtered
  7. customthe solvent evaporated
  8. customThe crude was purified by flash chromatography
  9. washeluting with DCM-MeOH—NH4OH (98:2:0.2)

出典と根拠

ORDレコード
ord-155b10483edf4f4aba22277effd8460e
出典データセット
uspto-grants-2010_06
特許番号
US07727988B2

反応ノート

読み込み中…