Sodium Iodide → HCID 86724072, compound

HRID 1748723Notes

Reaction equation

HRID 1748723 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[S:15][CH2:14][C:13](=[O:16])[NH:12][C:11]2[N:17]([CH3:26])[N:18]=[C:19]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=3)[C:10]1=2.C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[Na+].Br[CH2:36][C:37]([O:39][CH3:40])=[O:38]>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[S:15][CH2:14][C:13](=[O:16])[N:12]([CH2:36][C:37]([O:39][CH3:40])=[O:38])[C:11]2[N:17]([CH3:26])[N:18]=[C:19]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=3)[C:10]1=2

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 60984Methyl bromoacetateHCID 136348422HCID 136348422, compound

Product 1

HCID 86724072HCID 86724072, compoundYield 28.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-(2,4-dichloro-phenyl)-1-methyl-3-(pyridine-2-yl)-6,8-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7-(4H)-one (0.50 g, 1.2 mmol, prepared using C from Example 2 step B with thioglycolic acid and 2,4-dichloro-benzaldehyde) in anhydrous DMF was added cesium carbonate (0.804 g, 2.5 mmol), sodium iodide (0.370 g, 2.5 mmol) and methyl bromoacetate (0.128 mL, 1.4 mmol). The resulting mixture was stirred at rt for about 3 h, and then partitioned between ethyl acetate (50 mL) and water (25 mL). The layers were separated and the organic layer was washed with 5% aqueous sodium bicarbonate (2×25 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (SiO2, DCM/ethyl acetate 9:1) to give methyl 2-(4-(2,4-dichlorophenyl)-1-methyl-7-oxo-3-(pyridin-2-yl)-6,7-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-8(4H)-yl)acetate (0.16 g, 0.34 mmol, 28%) as a white solid: 1H-NMR (CDCl3, Bruker 400 MHz) 3.34 (1 H, d, J=17 Hz), 3.46 (1 H, dd, J=17 Hz, 2 Hz), 3.83 (3 H, s), 3.88 (3 H, s), 4.72 (1 H, d, J=15 Hz), 4.87 (1 H, d, J=15 Hz), 6.63 (1 H, d, J=9 Hz), 6.78 (1 H, d, J=2 Hz), 6.96-7.05 (2 H, m), 7.43 (1 H, d, J=2 Hz), 7.57 (1 H, dt, J=8 Hz, 2 Hz), 7.82-7.88 (1 H, m), 8.35 (1 H, m)

Workup

  1. custompartitioned between ethyl acetate (50 mL) and water (25 mL)
  2. customThe layers were separated
  3. washthe organic layer was washed with 5% aqueous sodium bicarbonate (2×25 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography (SiO2, DCM/ethyl acetate 9:1)

Sources & evidence

ORD record
ord-81c04512bbb24767b15f53a9a086f4ab
Source dataset
uspto-grants-2015_10
Patent number
US09150592B2

Reaction notes

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