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

HRID 1661073Notes

Reaction equation

HRID 1661073 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][C:14]=1[O:15][CH3:16])[C:7]1([CH2:11][CH2:10][NH:9][CH2:8]1)[CH2:6][CH2:5]2.Cl[CH2:18][CH2:19][CH2:20][S:21][C:22]1[N:23]([CH3:34])[C:24]([C:27]2[S:31][C:30]([CH3:32])=[N:29][C:28]=2[CH3:33])=[N:25][N:26]=1.C([O-])([O-])=O.[K+].[K+].[Na+].[I-]>CN1C(=O)CCC1>[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][C:14]=1[O:15][CH3:16])[C:7]1([CH2:11][CH2:10][N:9]([CH2:18][CH2:19][CH2:20][S:21][C:22]3[N:23]([CH3:34])[C:24]([C:27]4[S:31][C:30]([CH3:32])=[N:29][C:28]=4[CH3:33])=[N:25][N:26]=3)[CH2:8]1)[CH2:6][CH2:5]2

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 446278985-(5-(3-chloropropylthio)-4-methyl-4H-1,2,4-triazol-3-yl)-2,4-dimethylthiazoleHCID 592339355-Chloro-6-methoxy-2,3-dihydrospiro[indene-1,3'-pyrrolidine]

Product 1

HCID 674289485-(5-(3-(5-chloro-6-methoxy-2,3-dihydrospiro[indene-1,3'-pyrrolidine]-1'-yl)propylthio)-4-methyl-4H-1,2,4-triazol-3-yl)-2,4-dimethylthiazole hydrochlorideYield 15.4%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
70 °C

Procedure

The mixture of 5-chloro-6-methoxy-2,3-dihydrospiro[indene-1,3′-pyrrolidine] (Prep19, 58 mg, 0.24 mmol), 5-(5-(3-chloropropylthio)-4-methyl-4H-1,2,4-triazol-3-yl)-2,4-dimethylthiazole (Prep28, 50 mg, 0.17 mmol), K2CO3 (68.5 mg, 0.50 mmol) and NaI (24.5 mg, 0.50 mmol) in NMP (1 ml) was warmed to 70° C., and stirred overnight. The mixture was extracted with EA (5 ml×2). The combined organic layers were washed with Sat. NaHCO3, brine and dried over Na2SO4. The organic layer was concentrated in vacuo to afford crude product. The crude was purified by P-TLC and P-HPLC and treated with a 1N solution of HCl in ether, then freeze-dried to afford title compound (10 mg, y=11.98%).

Workup

  1. extractionThe mixture was extracted with EA (5 ml×2)
  2. washThe combined organic layers were washed with Sat. NaHCO3, brine
  3. dry with materialdried over Na2SO4
  4. concentrationThe organic layer was concentrated in vacuo
  5. customto afford crude product
  6. customThe crude was purified by P-TLC and P-HPLC
  7. additiontreated with a 1N solution of HCl in ether
  8. customfreeze-dried

Sources & evidence

ORD record
ord-36c345e863d84a0499163804e437e8b9
Source dataset
uspto-grants-2011_10
Patent number
US08030322B2

Reaction notes

Loading…