Sodium Iodide → (-)-GSK598809 hydrochloride

HRID 2384563ノート

反応式

HRID 2384563 の反応式
[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

参加物

7

反応物 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 回

生成物 1

HCID 67021274(-)-GSK598809 hydrochloride

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
60 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-fe69813af9144b339b9b36eba3b165e9
出典データセット
uspto-grants-2012_09
特許番号
US08263782B2

反応ノート

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