Dimethylformamide → HCID 59252802, compound

HRID 563387Notes

Reaction equation

HRID 563387 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([CH:10]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:11]([CH3:21])([CH3:20])[C:12]([NH:14][C:15]3[S:16][CH:17]=[CH:18][N:19]=3)=[O:13])=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.ClS([N:32]=[C:33]=O)(=O)=O.CN(C=O)C>C(#N)C>[C:33]([C:3]1[C:4]2[C:9](=[CH:8][CH:7]=[C:6]([CH:10]([C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:11]([CH3:21])([CH3:20])[C:12]([NH:14][C:15]3[S:16][CH:17]=[CH:18][N:19]=3)=[O:13])[CH:5]=2)[NH:1][CH:2]=1)#[N:32]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 70918Chlorosulfonyl isocyanateHCID 59252846HCID 59252846, compound

Product 1

HCID 59252802HCID 59252802, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 3-(1H-indol-5-yl)-2,2-dimethyl-3-phenyl-N-(thiazol-2-yl)propanamide (Example 101, 25 mg, 0.067 mmol) in anhydrous acetonitrile (1 mL) was added chlorosulfonyl isocyanate (0.007 mL, 0.074 mmol) at 0° C. under argon. The reaction mixture was stirred at 0° C. for 30 min before anhydrous DMF (0.006 mL, 0.074 mmol) was added. After the reaction mixture was stirred at 0° C. for 30 min and at rt for 1 hr, it was concentrated, mixed with saturated aqueous sodium bicarbonate solution (5 mL), and extracted with dichloromethane (10 mL). The dichloromethane extract was dried (Na2SO4) and concentrated. Silica gel flash chromatography gave 3-(3-cyano-1H-indol-5-yl)-2,2-dimethyl-3-phenyl-N-(thiazol-2-yl)propanamide (Example 108, 11 mg, 0.027 mmol, 41% yield) as a white solid. MS found: (M+H)+=401. 1H-NMR (400 MHz, Acetone-d6): δ ppm 11.15 (1 H, s) 10.48 (1H, s) 8.06 (1H, d, J=2.40 Hz) 7.78 (1H, s) 7.46-7.53 (3H, m) 7.39 (1 H, d, J=8.65 Hz) 7.35 (1H, d, J=3.56 Hz) 7.28 (2H, t, J=7.38 Hz) 7.18 (1H, t, J=7.38 Hz) 7.04 (1H, d, J=3.56 Hz) 5.04 (1H, s) 1.51 (6H, d, J=2.54 Hz).

Workup

  1. additionwas added
  2. concentrationit was concentrated
  3. additionmixed with saturated aqueous sodium bicarbonate solution (5 mL)
  4. extractionextracted with dichloromethane (10 mL)
  5. extractionThe dichloromethane extract
  6. dry with materialwas dried (Na2SO4)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-f0b1e71563dc4eccada8c66af1798bf5
Source dataset
uspto-grants-2011_11
Patent number
US08067447B2

Reaction notes

Loading…