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

HRID 12753Notes

Reaction equation

HRID 12753 reaction equation
[F:1][C:2]([F:16])([F:15])[C:3]1[CH:8]=[CH:7][C:6]([C@:9]23[CH2:14][C@H:13]2[CH2:12][NH:11][CH2:10]3)=[CH:5][CH:4]=1.[Cl:17][CH2:18][CH2:19][CH2:20][N:21]1[CH:26]=[C:25]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:24](=[O:33])[NH:23][C:22]1=[O:34].[Na+].[I-].[NH4+].[Cl-]>CN(C=O)C>[ClH:17].[C:27]1([C:25]2[C:24](=[O:33])[NH:23][C:22](=[O:34])[N:21]([CH2:20][CH2:19][CH2:18][N:11]3[CH2:12][C@H:13]4[C@:9]([C:6]5[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:15])[F:16])=[CH:8][CH:7]=5)([CH2:14]4)[CH2:10]3)[CH:26]=2)[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 25517Ammonium ChlorideHCID 589941861-(3-chloropropyl)-5-phenyl-2,4(1H,3H)-pyrimidinedioneHCID 59337591(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane

Product 1

HCID 686934935-phenyl-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo-[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione hydrochlorideYield 88.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of (1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane (Prep4, 40 mg) 1-(3-chloropropyl)-5-phenyl-2,4(1H,3H)-pyrimidinedione (Prep 4, 55 mg), TEA (0.050 mL) and NaI cat. Amount, in DMF (0.5 mL) was heated at 100° C. for 24 hours. Aqueous saturated NH4Cl solution was then added to the mixture and then it was extracted with DCM. The organic phase was dried and concentrated in vacuo. The crude product was purified by a SCX cartridge to give 77 mg of the title compound as free base. HCl (1M in diethyl ether) was added to a solution of the free base in dichloromethane. The mixture was evaporated and the residue triturated with diethyl ether to give the title compound (78 mg).

Workup

  1. extractionit was extracted with DCM
  2. customThe organic phase was dried
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by a SCX cartridge

Sources & evidence

ORD record
ord-6ec9f3d9adb8408a88df599667c67d5b
Source dataset
uspto-grants-2010_06
Patent number
US07727988B2

Reaction notes

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