Sodium Iodide → 5-(5-(3-(5-fluoro-2,3-dihydrospiro[indene-1,3'-pyrrolidine]-1'-yl)propylthio)-4-methyl-4H-1,2,4-triazol-3-yl)-2,4-dimethylthiazole

HRID 1661076Notes

Reaction equation

HRID 1661076 reaction equation
Cl[CH2:2][CH2:3][CH2:4][S:5][C:6]1[N:7]([CH3:18])[C:8]([C:11]2[S:15][C:14]([CH3:16])=[N:13][C:12]=2[CH3:17])=[N:9][N:10]=1.C([O-])([O-])=O.[K+].[K+].Cl.[F:26][C:27]1[CH:28]=[C:29]2[C:37](=[CH:38][CH:39]=1)[C:32]1([CH2:36][CH2:35][NH:34][CH2:33]1)[CH2:31][CH2:30]2.[Na+].[I-]>CN1C(=O)CCC1.O>[F:26][C:27]1[CH:28]=[C:29]2[C:37](=[CH:38][CH:39]=1)[C:32]1([CH2:36][CH2:35][N:34]([CH2:2][CH2:3][CH2:4][S:5][C:6]3[N:7]([CH3:18])[C:8]([C:11]4[S:15][C:14]([CH3:16])=[N:13][C:12]=4[CH3:17])=[N:9][N:10]=3)[CH2:33]1)[CH2:31][CH2:30]2

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 446278985-(5-(3-chloropropylthio)-4-methyl-4H-1,2,4-triazol-3-yl)-2,4-dimethylthiazoleHCID 674294815-Fluoro-2,3-dihydrospiro[indene-1,3'-pyrrolidine]hydrochloride salt

Product 1

HCID 247585915-(5-(3-(5-fluoro-2,3-dihydrospiro[indene-1,3'-pyrrolidine]-1'-yl)propylthio)-4-methyl-4H-1,2,4-triazol-3-yl)-2,4-dimethylthiazoleYield 36.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a solution of 5-(5-(3-chloropropylthio)-4-methyl-4H-1,2,4-triazol-3-yl)-2,4-dimethylthiazole (Prep28, 70 mg, 0.23 mmol) in dry NMP (1 ml), K2CO3 (0.145 g, 1.05 mmol) was added and stirred for 10 min. Then 5-fluoro-2,3-dihydrospiro[indene-1,3′-pyrrolidine]hydrochloride salt (Prep14, 88 mg, 0.39 mmol) and NaI (0.07 g, 0.47 mmol) were added and stirred overnight at 65° C. Water was then added and the solution was extracted with ethyl acetate (2×10 ml). The organic phase was washed with brine, dried over Na2SO4 and concentrated in vacuo. The crude product was purified by P-HPLC to give 38 mg of the title compound (y=36%).

Workup

  1. stirringstirred overnight at 65° C
  2. extractionthe solution was extracted with ethyl acetate (2×10 ml)
  3. washThe organic phase was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by P-HPLC

Sources & evidence

ORD record
ord-2bfbf5dcbb324a87bd506cb5bd9582be
Source dataset
uspto-grants-2011_10
Patent number
US08030322B2

Reaction notes

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