Water → HCID 178433404, compound

HRID 1661072Notes

Reaction equation

HRID 1661072 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[C:7]1([CH2:11][CH2:10][NH:9][CH2:8]1)[CH2:6][CH2:5]2.C([O-])([O-])=O.[K+].[K+].[Na+].[I-].O.[Cl:24][CH2:25][CH2:26][CH2:27][S:28][C:29]1[N:33]=[C:32]([C:34]2[O:38][CH:37]=[N:36][C:35]=2[CH3:39])[NH:31][N:30]=1>CN(C=O)C>[ClH:24].[Br:1][C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[C:7]1([CH2:11][CH2:10][N:9]([CH2:25][CH2:26][CH2:27][S:28][C:29]3[NH:30][N:31]=[C:32]([C:34]4[O:38][CH:37]=[N:36][C:35]=4[CH3:39])[N:33]=3)[CH2:8]1)[CH2:6][CH2:5]2

Participants

7

Reactant 5

HCID 962WaterHCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 592339285-Bromo-2,3-dihydrospiro[1H-indene-1,3′-pyrrolidine]HCID 67430173HCID 67430173, compound

Product 1

HCID 178433404HCID 178433404, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 5-bromo-2,3-dihydrospiro[indene-1,3′-pyrrolidine] (Prep4, 0.04 g, 0.159 mmol) in dry DMF (1 ml), 3-[(3-chloropropyl)thio]-5-(4-methyl-1,3-oxazol-5-yl)-1H-1,2,4-triazole (reference procedure for preparation described in WO05/080382, 0.058 g, 0.213 mmol) was added. Then, K2CO3 (0.029 g) and NaI (0.028 g) were added and the mixture was heated at 80° C. for 24 hours. Water was then added and the solution was extracted with ethyl acetate. The organic phase was washed with brine, dried over Na2SO4 and concentrated in vacuo. The crude product was purified by a silica SPE cartridge eluting with dichloromethane/methanol from 100/0 to 98/to obtain 0.036 g of the title compound as free base. To a solution of this material in dichloromethane (1 mL) was added 0.073 mL of HCl (1M in Et2O), the solvent was evaporated in vacuo and the material thus obtained triturated with Et2O to give 32 mg of the title compound as a white slightly hygroscopic solid.

Workup

  1. additionwas added
  2. extractionthe solution was extracted with ethyl acetate
  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 a silica SPE cartridge
  7. washeluting with dichloromethane/methanol from 100/0 to 98/to

Sources & evidence

ORD record
ord-750b14ebc5f04c019266bfdf4b647ef7
Source dataset
uspto-grants-2011_10
Patent number
US08030322B2

Reaction notes

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