Sodium Iodide → (-)-GSK598809 hydrochloride

HRID 2061935Notes

Reaction equation

HRID 2061935 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[C@:12]12[CH2:17][C@H:16]1[CH2:15][NH:14][CH2:13]2.[Cl:18][CH2:19][CH2:20][CH2:21][S:22][C:23]1[N:27]([CH3:28])[C:26]([C:29]2[O:33][CH:32]=[N:31][C:30]=2[CH3:34])=[N:25][N:24]=1.C([O-])([O-])=O.[K+].[K+].[Na+].[I-]>CN(C=O)C.C(OCC)(=O)C>[ClH:18].[F:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[C@:12]12[CH2:17][C@H:16]1[CH2:15][N:14]([CH2:19][CH2:20][CH2:21][S:22][C:23]1[N:27]([CH3:28])[C:26]([C:29]3[O:33][CH:32]=[N:31][C:30]=3[CH3:34])=[N:25][N:24]=1)[CH2:13]2

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 446279943-[(3-Chloropropyl)thio]-4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazoleHCID 59346768(1S,5R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane2×

Product 1

HCID 67021274(-)-GSK598809 hydrochloride

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

The free base of the title compound was prepared in analogy to the method described in Example 1 from (1S,5R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane. A mixture of (1S,5R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane (Preparation 39, 727 mg, 2.97 mmol), 3-[(3-Chloropropyl)thio]-4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazole (Preparation 14, 3.6 mmol.), K2CO3 (3.6 mmol.) and NaI (2.97 mmol) in DMF anhydrous was heated at 60° C. for 24 h. After elimination of the solvent under vacuo, the residue was dissolved in ethyl acetate and the organic layer was washed with saturated aqueous NaHCO3 and dried over Na2SO4. This solution was filtered and the filtrate was concentrated in vacuo. The crude was purified by flash chromatography (dichloromethane to 10% MeOH in dichloromethane) to give 940 mg of the free base of the title compound.

Workup

  1. washthe organic layer was washed with saturated aqueous NaHCO3
  2. dry with materialdried over Na2SO4
  3. filtrationThis solution was filtered
  4. concentrationthe filtrate was concentrated in vacuo
  5. customThe crude was purified by flash chromatography (dichloromethane to 10% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-39027641be48468cbee79a40f3fd20cb
Source dataset
uspto-grants-2012_10
Patent number
US08283474B2

Reaction notes

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