Acetic Acid → 1-{3-[1-(4-chlorophenyl)-3-azabicyclo[3.1.0]hex-3-yl]propyl}-5-iodo-3-(phenylcarbonyl)-2,4(1H,3H)-pyrimidinedione

HRID 12708

反応式

HRID 12708 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]23[CH2:13][CH:12]2[CH2:11][NH:10][CH2:9]3)=[CH:4][CH:3]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[I:32][C:33]1[C:34](=[O:52])[N:35]([C:44]([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)=[O:45])[C:36](=[O:43])[N:37]([CH2:39][CH2:40][CH:41]=O)[CH:38]=1>ClCCCl.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]23[CH2:13][CH:12]2[CH2:11][N:10]([CH2:41][CH2:40][CH2:39][N:37]2[CH:38]=[C:33]([I:32])[C:34](=[O:52])[N:35]([C:44]([C:46]4[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=4)=[O:45])[C:36]2=[O:43])[CH2:9]3)=[CH:6][CH:7]=1

参加物

7

反応物 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 101303311-(4-Chlorophenyl)-3-azabicyclo[3.1.0]hexaneHCID 593375793-[5-iodo-2,4-dioxo-3-(phenylcarbonyl)-3,4-dihydro-1(2H)-pyrimidinyl]propanal

生成物 1

HCID 866159461-{3-[1-(4-chlorophenyl)-3-azabicyclo[3.1.0]hex-3-yl]propyl}-5-iodo-3-(phenylcarbonyl)-2,4(1H,3H)-pyrimidinedione

試薬・触媒・溶媒 2

HCID 111,2-Dichloroethane溶媒HCID 962Water溶媒

反応条件

温度
0 °C

実験手順

1-(4-chlorophenyl)-3-azabicyclo[3.1.0]hexane (racemate, reference procedure for preparation reported in WO2005/080382, 136 mg, 0.703 mmol), acetic acid (0.060 mL, 1.055 mmol), and sodium triacetoxyborohydride (164 mg, 0.774 mmol) were added at 0° C. to a solution of 3-[5-iodo-2,4-dioxo-3-(phenylcarbonyl)-3,4-dihydro-1(2H)-pyrimidinyl]propanal (P38, 280 mg, 0.703 mmol) in 1,2-Dichloroethane (DCE) (8.7 ml). The mixture was stirred at 0° C. for further 4 hours. Water was added and the reaction mixture was concentrated removing the solvent under vacuum. The residue was re-dissolved in ethyl acetate and the organic layer washed with aqueous saturated NaHCO3 solution. The aqueous solution was extracted with ethyl acetate (3×20 ml). The organic layers were collected, dried over Na2SO4, filtrated and evaporated. The crude was purified by chromatography (SPE Si 10 g) with toluene/acetone 8/2. The title compound was recovered as a light yellow oil (190 mg).

後処理

  1. concentrationthe reaction mixture was concentrated
  2. customremoving the solvent under vacuum
  3. dissolutionThe residue was re-dissolved in ethyl acetate
  4. washthe organic layer washed with aqueous saturated NaHCO3 solution
  5. extractionThe aqueous solution was extracted with ethyl acetate (3×20 ml)
  6. customThe organic layers were collected
  7. dry with materialdried over Na2SO4
  8. filtrationfiltrated
  9. customevaporated
  10. customThe crude was purified by chromatography (SPE Si 10 g) with toluene/acetone 8/2
  11. customThe title compound was recovered as a light yellow oil (190 mg)

出典と根拠

ORDレコード
ord-99bac3bd46b747efbe532d4ce15019df
出典データセット
uspto-grants-2010_06
特許番号
US07727988B2

関連ノート

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