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

HRID 1925064Notes

Reaction equation

HRID 1925064 reaction equation
Cl[CH2:2][CH2:3][CH2:4][N:5]1[CH2:10][C@H:9]2[C@:7]([C:11]3[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=3)([CH2:8]2)[CH2:6]1.[OH:21][C:22]1[NH:27][C:26](=[O:28])[N:25]=[CH:24][C:23]=1[C:29]1[O:33][N:32]=[C:31]([CH3:34])[N:30]=1.[I-].[Na+].CCN(C(C)C)C(C)C>CS(C)=O.CCOC(C)=O>[CH3:34][C:31]1[N:30]=[C:29]([C:23]2[C:22](=[O:21])[NH:27][C:26](=[O:28])[N:25]([CH2:2][CH2:3][CH2:4][N:5]3[CH2:10][C@H:9]4[C@:7]([C:11]5[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=5)([CH2:8]4)[CH2:6]3)[CH:24]=2)[O:33][N:32]=1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 81531DiisopropylethylamineHCID 59337588(1S,5R)-3-(3-chloropropyl)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexaneHCID 178434736HCID 178434736, compound

Product 1

HCID 252532945-(3-methyl-1,2,4-oxadiazol-5-yl)-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedioneYield 20%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

In a 0.5/2 mL sealed MW vial (1S,5R)-3-(3-chloropropyl)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane (Prep5, 62.6 mg, 0.206 mmol) was dissolved in Dimethyl Sulfoxide (DMSO) (0.8 ml), and, 6-hydroxy-5-(3-methyl-1,2,4-oxadiazol-5-yl)-2(1H)-pyrimidinone (Prep33, 40 mg, 0.206 mmol), Sodium iodide (46.3 mg, 0.309 mmol) and Dipea (0.126 mL, 0.721 mmol) were then added. The red mixture so obtained was heated at 120° C. for 4 h, then left at 80° C. overnight. The day after DIPEA (0.054 mL, 0.310 mmol) was added and the mixture and the heated at 120° C. for further 4 h. The mixture was treated with EtOAc and washed with NH4Cl sat. sol. The organic phase was dried over Na2SO4 anhydrous, filtered and evaporated under reduced pressure providing a brown residue. The crude was purified first by SCX cartridge and then by Biotage Si 12+M cartridge with a gradient of DCM/DCM/MeOH (9:1). 19 mg of the title compound were obtained as a yellow oil.

Workup

  1. customThe red mixture so obtained
  2. temperaturethe mixture and the heated at 120° C. for further 4 h
  3. washwashed with NH4Cl sat. sol. The organic phase
  4. dry with materialwas dried over Na2SO4 anhydrous
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customproviding a brown residue
  8. customThe crude was purified first by SCX cartridge

Sources & evidence

ORD record
ord-b2f050c596fd4909ae652e5384d1dd1a
Source dataset
uspto-grants-2012_05
Patent number
US08178549B2

Reaction notes

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