Sodium Iodide → 5-(5-(3-(6-chloro-2,3-dihydrospiro[indene-1,3'-pyrrolidine]-1'-yl)propylthio)-4-methyl-4H-1,2,4-triazol-3-yl)-2,4-dimethylthiazole hydrochloride

HRID 1661082Notes

Reaction equation

HRID 1661082 reaction equation
[Cl:1][C:2]1[CH:14]=[C:13]2[C:5]([CH2:6][CH2:7][C:8]32[CH2:12][CH2:11][NH:10][CH2:9]3)=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].[I-].[Na+].Cl[CH2:24][CH2:25][CH2:26][S:27][C:28]1[N:29]([CH3:40])[C:30]([C:33]2[S:37][C:36]([CH3:38])=[N:35][C:34]=2[CH3:39])=[N:31][N:32]=1>CN1C(=O)CCC1.O>[ClH:1].[Cl:1][C:2]1[CH:14]=[C:13]2[C:5]([CH2:6][CH2:7][C:8]32[CH2:12][CH2:11][N:10]([CH2:24][CH2:25][CH2:26][S:27][C:28]2[N:29]([CH3:40])[C:30]([C:33]4[S:37][C:36]([CH3:38])=[N:35][C:34]=4[CH3:39])=[N:31][N:32]=2)[CH2:9]3)=[CH:4][CH:3]=1

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 592339126-Chloro-2,3-dihydrospiro[indene-1,3'-pyrrolidine]

Product 1

HCID 247589465-(5-(3-(6-chloro-2,3-dihydrospiro[indene-1,3'-pyrrolidine]-1'-yl)propylthio)-4-methyl-4H-1,2,4-triazol-3-yl)-2,4-dimethylthiazole hydrochloride

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
70 °C

Procedure

The mixture of 6-chloro-2,3-dihydrospiro[indene-1,3′-pyrrolidine] (Prep47, 100 mg, 0.37 mmol), K2CO3 (110 mg, 0.8 mmol), sodium iodide (80 mg, 0.53 mmol), and 5-(5-(3-chloropropylthio)-4-methyl-4H-1,2,4-triazol-3-yl)-2,4-dimethylthiazole (Prep28, 80 mg, 0.28 mmol) in NMP (4 ml) was warmed to 70° C. The mixture was stirred at 70° C. overnight. The mixture diluted with water (20 ml), extracted with EA (10 ml). The organic layers were combined and washed with Sat. NaHCO3, Sat. brine and dried over anhydrous Na2SO4. The organics was evaporated under vacuum to get crude product. The crude product was purified by P-TLC (TLC analysis performed by eluting with PE/EA 1:1), then P-HPLC. The free base of the compound was then converted into the title compound (treatment with 1 eq of 1N HCl) and dried under vacuum to give the desired product as white solid (20 mg, y=11.4%).

Workup

  1. extractionextracted with EA (10 ml)
  2. washwashed with Sat. NaHCO3, Sat. brine
  3. dry with materialdried over anhydrous Na2SO4
  4. customThe organics was evaporated under vacuum
  5. customto get crude product
  6. customThe crude product was purified by P-TLC (TLC analysis performed by eluting with PE/EA 1:1)

Sources & evidence

ORD record
ord-ed1a14192a304911a6e2c26cb45c5997
Source dataset
uspto-grants-2011_10
Patent number
US08030322B2

Reaction notes

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