Acetic Acid → 3-Benzoyl-5-iodo-1-{3-[(1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hex-3-yl]-propyl}-1H-pyrimidine-2,4-dione

HRID 12671

反応式

HRID 12671 の反応式
[C:1]([N:9]1[C:14](=[O:15])[C:13]([I:16])=[CH:12][N:11]([CH2:17][CH2:18][CH:19]=O)[C:10]1=[O:21])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:22][C:23]([F:37])([F:36])[C:24]1[CH:29]=[CH:28][C:27]([C@:30]23[CH2:35][C@H:34]2[CH2:33][NH:32][CH2:31]3)=[CH:26][CH:25]=1.CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCl.O>[C:1]([N:9]1[C:14](=[O:15])[C:13]([I:16])=[CH:12][N:11]([CH2:17][CH2:18][CH2:19][N:32]2[CH2:33][C@H:34]3[C@:30]([C:27]4[CH:26]=[CH:25][C:24]([C:23]([F:22])([F:37])[F:36])=[CH:29][CH:28]=4)([CH2:35]3)[CH2:31]2)[C:10]1=[O:21])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

参加物

7

反応物 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 593375793-[5-iodo-2,4-dioxo-3-(phenylcarbonyl)-3,4-dihydro-1(2H)-pyrimidinyl]propanalHCID 59337591(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane

生成物 1

HCID 675197023-Benzoyl-5-iodo-1-{3-[(1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hex-3-yl]-propyl}-1H-pyrimidine-2,4-dione収率 84.9%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

To a solution of 3-(3-benzoyl-5-iodo-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-propionaldehyde (Prep 38, 700 mg, 1.7 mmol) in dichloromethane (20 mL), (1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (Prep 4, 399 mg, 1.7 mmol), AcOH (158 mg, 2.5 mmol) and NaBH(AcO)3 (410 mg, 1.9 mmol) were added at 0° C. The mixture was stirred at 0° C. for further 1 hours. Water was added and the solvent was evaporated under vacuum, the residue re-dissolved in ethyl acetate and the mixture washed with a 5% solution of aqueous NaHCO3. The organic phase was dried (Na2SO4) and evaporated. The crude was purified by flash chromatography with DCM-MeOH—NH4OH (97-3-1) to give the title compound as a white solid (880 mg, 83% yield).

後処理

  1. customthe solvent was evaporated under vacuum
  2. dissolutionthe residue re-dissolved in ethyl acetate
  3. washthe mixture washed with a 5% solution of aqueous NaHCO3
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. customevaporated
  6. customThe crude was purified by flash chromatography with DCM-MeOH—NH4OH (97-3-1)

出典と根拠

ORDレコード
ord-74726e650c6f46b7980399e0dc3cc6f7
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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