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

HRID 12752Notes

Reaction equation

HRID 12752 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[S:28][CH:29]=[CH:30][CH:31]=2)[C:24](=[O:32])[NH:23][C:22]1=[O:33].[Na+].[I-].[NH4+].[Cl-]>CN(C=O)C>[ClH:17].[S:28]1[CH:29]=[CH:30][CH:31]=[C:27]1[C:25]1[C:24](=[O:32])[NH:23][C:22](=[O:33])[N:21]([CH2:20][CH2:19][CH2:18][N:11]2[CH2:12][C@H:13]3[C@:9]([C:6]4[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:15])[F:16])=[CH:8][CH:7]=4)([CH2:14]3)[CH2:10]2)[CH:26]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 25517Ammonium ChlorideHCID 59337591(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexaneHCID 593375931-(3-chloropropyl)-5-(2-thienyl)-2,4(1H,3H)-pyrimidinedione

Product 1

HCID 675197005-(2-thienyl)-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione hydrochlorideYield 59.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane (Prep4, 40 mg), 1-(3-chloropropyl)-5-(2-thienyl)-2,4(1H,3H)-pyrimidinedione (Prep15, 57 mg), NaI catalytic amount and TEA (0.050 mL) 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 phases were dried and concentrated in vacuo. The crude product was purified by a SCX cartridge and then by preparative HPLC [(column: XTerra Prep MS C18 30×150 mm, 10 uM; mobile phase A: H2O+0.1% formic acid, mobile phase B: acetonitrile+0.1% formic acid, gradient: from 1 to 25% (B) in 10 min, from 25 to 90% in 4.50 min, from 90 to 100% in 0.50 min; flow rate: 40 mL/min; UV wavelength range: 210-400 nm, ionization: ES+ and ES−; mass range: 150-900 amu (ES+)], to give 52 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 (40 mg).

Workup

  1. extractionit was extracted with DCM
  2. customThe organic phases were dried
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by a SCX cartridge
  5. waitfrom 25 to 90% in 4.50 min
  6. waitfrom 90 to 100% in 0.50 min

Sources & evidence

ORD record
ord-d946bc7859824ae3a789804174c66f44
Source dataset
uspto-grants-2010_06
Patent number
US07727988B2

Reaction notes

Loading…