Sodium Iodide → 5-[5-[3-(6-Chlorospiro[1,2-dihydroindene-3,3'-pyrrolidine]-1'-yl)propylsulfanyl]-4-methyl-1,2,4-triazol-3-yl]-2,4-dimethyl-1,3-thiazole

HRID 1661074Notes

Reaction equation

HRID 1661074 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.[Cl: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>[Cl: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 674279925-Chloro-2,3-dihydrospiro[indene-1,3'-pyrrolidine] hydrochloride

Product 1

HCID 247584815-[5-[3-(6-Chlorospiro[1,2-dihydroindene-3,3'-pyrrolidine]-1'-yl)propylsulfanyl]-4-methyl-1,2,4-triazol-3-yl]-2,4-dimethyl-1,3-thiazoleYield 52.3%

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 (0.144 g, 1 mmol) was added and stirred for 10 min, then 5-chloro-2,3-dihydrospiro[indene-1,3′-pyrrolidine]hydrochloride (Prep10, 88 mg, 0.36 mmol) and NaI (0.07 g) were added and stirred for 23 h 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 (TLC analysis performed by eluting with EA/MeOH 80:10) to give 57 mg of the title compound (y=52%).

Workup

  1. stirringstirred for 23 h 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 (TLC analysis performed by eluting with EA/MeOH 80:10)

Sources & evidence

ORD record
ord-f6274fe5eb984b3f879c356e9f899018
Source dataset
uspto-grants-2011_10
Patent number
US08030322B2

Reaction notes

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