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

HRID 12813Notes

Reaction equation

HRID 12813 reaction equation
[O:1]=[C:2]1[NH:7][C:6](=[O:8])[C:5]([C:9]2[CH:14]=[N:13][CH:12]=[CH:11][N:10]=2)=[CH:4][N:3]1[CH2:15][CH2:16][CH:17]=O.[F:19][C:20]([F:34])([F:33])[C:21]1[CH:26]=[CH:25][C:24]([C@:27]23[CH2:32][C@H:31]2[CH2:30][NH:29][CH2:28]3)=[CH:23][CH:22]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[OH-].[Na+]>ClC(Cl)C.CO.CC(O)=O>[N:10]1[CH:11]=[CH:12][N:13]=[CH:14][C:9]=1[C:5]1[C:6](=[O:8])[NH:7][C:2](=[O:1])[N:3]([CH2:15][CH2:16][CH2:17][N:29]2[CH2:30][C@H:31]3[C@:27]([C:24]4[CH:23]=[CH:22][C:21]([C:20]([F:19])([F:34])[F:33])=[CH:26][CH:25]=4)([CH2:32]3)[CH2:28]2)[CH:4]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 58994178HCID 58994178, compoundHCID 59337591(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane

Product 1

HCID 247582255-(2-pyrazinyl)-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedioneYield 45%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 22036585Dichloroethane methanolSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 3-(2,4-dioxo-5-pyrazin-2-yl-3,4-dihydro-2H-pyrimidin-1-yl)-propionaldehyde (Prep127, 0.38 mmol), (1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (Prep4, 86 mg, 0.38 mmol), and AcOH (26 μl) in dichloroethane-MeOH (10-0.5, 4 ml) was cooled to 0° C. NaBH(AcO)3 (84 mg, 0.40 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 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 78 mg of the title compound (45% yield).

Workup

  1. extractionThe product was 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)

Sources & evidence

ORD record
ord-149b00dae9604dfbb56229b89e70d7dc
Source dataset
uspto-grants-2010_06
Patent number
US07727988B2

Reaction notes

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