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 12811Notes

Reaction equation

HRID 12811 reaction equation
[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

Participants

7

Reactant 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

Product 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 dihydrochlorideYield 12%

Reagents, catalysts & solvents 1

HCID 22036585Dichloroethane methanolSolvent

Conditions

Temperature
0 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-8844db28fd2443efafc8ecd669fe3a11
Source dataset
uspto-grants-2010_06
Patent number
US07727988B2

Reaction notes

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