Nitrogen → HCID 16074767, compound

HRID 2193914Notes

Reaction equation

HRID 2193914 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]([C:7]1[S:8][C:9]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[CH:10][C:11]=1[NH:12][C:13](=[O:22])[C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=1[Cl:21])=[O:6].N#N.I[CH:32]([CH3:34])[CH3:33]>CN(C)C=O>[CH3:3][O:4][C:5]([C:7]1[S:8][C:9]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[CH:10][C:11]=1[N:12]([C:13](=[O:22])[C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=1[Cl:21])[CH:32]([CH3:34])[CH3:33])=[O:6]

Participants

6

Reactant 4

HCID 947NitrogenHCID 6362Isopropyl iodideHCID 24758Sodium hydrideHCID 20775751HCID 20775751, compound

Product 1

HCID 16074767HCID 16074767, compoundYield 55%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Sodium Hydride (60% dispersion in oil, 190 mg, 5.2 mmol) was added to an ice-cold solution of 3-(2,4-Dichloro-benzoylamino)-5-phenyl-thiophene-2-carboxylic acid methyl ester (2) (1.5 g, 3.69 mmol) in 350 ml of N,N-dimethylformamide in an atmosphere of N2. After 5 min, 2-Iodo-propane (941 mg, 5.54 mmol) was added to the solution and then the reaction mixture was stirred for 30 min at 0° C. and 64 h at room temperature. The mixture was partitioned between ether (200 mL) and water (350 mL) and the organic layer was separated. The aqueous phase was washed twice with ether (2×70 mL) and the combined ether layer was dried (MgSO4), concentrated and the residue was purified by flash chromatography (10% EtOAc/Hexane) to obtain 908 mg (55%) of 3-[(2,4-Dichloro-benzoyl)-isopropyl-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester. NMR 1H (CDCl3, 400 MHz): Rotamere 95/05: 7.54 ppm (dd, 2H, Haro); 7.49-7.35 ppm (m, 3H, Haro); 7.29-7.25 ppm (m, 2H, Haro); 7.15 ppm (d, 1H, Haro); 7.05 ppm (d, 1H, Haro) 5.09 ppm (hex, 1H, N—CH(CH3), major rotamere); 3.99 ppm (hex, N—CH(CH3), minor rotamere); 3.89 ppm (s, 3H); 1.40 ppm (d, 3H, N—CH(CH3), major rotamere); 1.28 ppm (d, N—CH(CH3), minor rotamere); 1.09 ppm (d, 3H, N—CH(CH3), major rotamere); 1.01 ppm (d, N—CH(CH3), minor rotamere).

Workup

  1. customThe mixture was partitioned between ether (200 mL) and water (350 mL)
  2. customthe organic layer was separated
  3. washThe aqueous phase was washed twice with ether (2×70 mL)
  4. dry with materialthe combined ether layer was dried (MgSO4)
  5. concentrationconcentrated
  6. customthe residue was purified by flash chromatography (10% EtOAc/Hexane)

Sources & evidence

ORD record
ord-09f2ea6ee224469f855c1ac0070b9dce
Source dataset
uspto-grants-2012_12
Patent number
US08329924B2

Reaction notes

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