Dimethylformamide → HCID 59252748, compound

HRID 563388Notes

Reaction equation

HRID 563388 reaction equation
P(Cl)(Cl)(Cl)=O.[NH:6]1[C:14]2[C:9](=[CH:10][C:11]([CH:15]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:16]([CH3:26])([CH3:25])[C:17]([NH:19][C:20]3[S:21][CH:22]=[CH:23][N:24]=3)=[O:18])=[CH:12][CH:13]=2)[CH:8]=[CH:7]1.[OH-].[Na+].CN([CH:38]=[O:39])C>>[CH:38]([C:8]1[C:9]2[C:14](=[CH:13][CH:12]=[C:11]([CH:15]([C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:16]([CH3:26])([CH3:25])[C:17]([NH:19][C:20]3[S:21][CH:22]=[CH:23][N:24]=3)=[O:18])[CH:10]=2)[NH:6][CH:7]=1)=[O:39]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 59252846HCID 59252846, compound

Product 1

HCID 59252748HCID 59252748, compoundYield 83%

Procedure

Phosphorus oxychloride (0.01 mL, 0.11 mmol) was added to anhydrous DMF (0.5 mL) under argon. The mixture was stirred at rt for 15 min before 3-(1H-indol-5-yl)-2,2-dimethyl-3-phenyl-N-(thiazol-2-yl)propanamide (Example 101, 18 mg, 0.048 mmol) was added. The reaction mixture was stirred at rt for 1 hr. Aqueous sodium hydroxide solution (1N, 2 mL) was added, the mixture was stirred at 80° C. for 8 min. The reaction mixture was quenched with saturated aqueous ammonium chloride solution (1 mL) and water (1 mL) and extracted with dichloromethane (10 mL). The dichloromethane extract was dried (Na2SO4) and concentrated. Silica gel flash chromatography gave 3-(3-formyl-1H-indol-5-yl)-2,2-dimethyl-3-phenyl-N-(thiazol-2-yl)propanamide (Example 109, 16 mg, 0.04 mmol, 83% yield) as a glassy solid. MS found: (M+H)+=404. 1H NMR (400 MHz, CDCl3) δ ppm 9.93-9.95 (1 H, s) 9.92 (1H, s) 9.25 (1H, s) 8.34 (1H, s) 7.66 (1H, d, J=3.05 Hz) 7.34-7.39 (3 H, m) 7.12-7.28 (5H, m) 6.92 (1H, d, J=3.56 Hz) 4.51 (1H, s) 1.42 (6H, s).

Workup

  1. additionwas added
  2. stirringthe mixture was stirred at 80° C. for 8 min
  3. customThe reaction mixture was quenched with saturated aqueous ammonium chloride solution (1 mL) and water (1 mL)
  4. extractionextracted with dichloromethane (10 mL)
  5. extractionThe dichloromethane extract
  6. dry with materialwas dried (Na2SO4)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-6dab3653ab694da6af2a5a1469857fc5
Source dataset
uspto-grants-2011_11
Patent number
US08067447B2

Reaction notes

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