Acetic Acid → 5-(3-pyridazinyl)-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione dihydrochloride

HRID 12811ノート

反応式

HRID 12811 の反応式
[ClH:1].[O:2]=[C:3]1[NH:8][C:7](=[O:9])[C:6]([C:10]2[N:11]=[N:12][CH:13]=[CH:14][CH:15]=2)=[CH:5][N:4]1[CH2:16][CH2:17][CH:18]=O.[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+].[OH-].[Na+]>ClC(Cl)C.CO>[ClH:1].[ClH:1].[N:12]1[CH:13]=[CH:14][CH:15]=[C:10]([C:6]2[C:7](=[O:9])[NH:8][C:3](=[O:2])[N:4]([CH2:16][CH2:17][CH2:18][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:5]=2)[N:11]=1

参加物

7

反応物 5

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 59337591(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexaneHCID 866159683-(2,4-dioxo-5-pyridazin-3-yl-3,4-dihydro-2H-pyrimidin-1-yl)-propionaldehyde hydrochloride

生成物 1

HCID 686946285-(3-pyridazinyl)-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione dihydrochloride収率 12%

試薬・触媒・溶媒 1

HCID 22036585Dichloroethane methanol溶媒

反応条件

温度
0 °C

実験手順

A solution of 3-(2,4-dioxo-5-pyridazin-3-yl-3,4-dihydro-2H-pyrimidin-1-yl)-propionaldehyde hydrochloride (Prep123, 100 mg, 0.35 mmol), (1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (Prep4, 80 mg, 0.35 mmol), and AcOH (21 mg, 0.35 mmol) in dichloroethane-MeOH (1-1, 4 ml) was cooled to 0° C. NaBH(AcO)3 (83 mg, 0.39 mmol) was added portionwise. The mixture was stirred at 0° C. for further one hour and then basified with 1N NaOH. The product was extracted with ethyl acetate. The organic phase was dried (Na2SO4) and evaporated. The residue was redissolved in DCM and stirred for 72 hours in the presence of PS-isocyanate (300 mg). The mixture was filtered and the solvent evaporated. The crude was triturated with diethyl ether to give 20 mg the free base of title compound (12% yield).

後処理

  1. extractionThe product was extracted with ethyl acetate
  2. dry with materialThe organic phase was dried (Na2SO4)
  3. customevaporated
  4. dissolutionThe residue was redissolved in DCM
  5. stirringstirred for 72 hours in the presence of PS-isocyanate (300 mg)
  6. filtrationThe mixture was filtered
  7. customthe solvent evaporated
  8. customThe crude was triturated with diethyl ether

出典と根拠

ORDレコード
ord-8844db28fd2443efafc8ecd669fe3a11
出典データセット
uspto-grants-2010_06
特許番号
US07727988B2

反応ノート

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