N-(5-tert-butyl-1,3,4-thiadiazol-2-yl)-5-chloro-2-methoxybenzamide → HCID 178490684, compound

HRID 717221Notes

Reaction equation

HRID 717221 reaction equation
[C:1]([C:5]1[S:9][C:8]([NH:10][C:11](=[O:21])[C:12]2[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:13]=2[O:19][CH3:20])=[N:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:22][C:23](C)([O-:25])[CH3:24].[K+].CN(C)C=O.O1CC[CH2:35][CH2:34]1>>[C:1]([C:5]1[S:9]/[C:8](=[N:10]\[C:11](=[O:21])[C:12]2[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:13]=2[O:19][CH3:20])/[N:7]([CH2:22][C@H:23]2[CH2:24][CH2:35][CH2:34][O:25]2)[N:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 3

HCID 2914804N-(5-tert-butyl-1,3,4-thiadiazol-2-yl)-5-chloro-2-methoxybenzamideHCID 21974620tetrahydrofuran N,N-dimethylformamideHCID 23665647Potassium tert-butoxide

Product 1

HCID 178490684HCID 178490684, compound

Conditions

Temperature
80 °C

Procedure

To a solution of Example 4A (200 mg, 0.62 mmol) in N,N-dimethylformamide/tetrahydrofuran (1:4, 10 mL) were added a solution of potassium tert-butoxide (Aldrich, 103 mg, 0.92 mmol) and Example IB (189 mg, 0.74 mmol). The reaction mixture was stirred at 80° C. for 16 h, cooled to room temperature, quenched with saturated aqueous NaHCO3 (10 mL). The aqueous layer was extracted with ethyl acetate (3×10 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography using an Analogix® Intelliflash280™ (SiO2, 0-1% methanol in dichloromethane) to afford the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.39 (s, 9H), 1.69-2.04 (m, 4H), 3.60-3.70 (m, 1H), 3.73-3.79 (m, 1H), 3.80 (s, 3H), 4.24 (dd, J=4.7, 15.0 Hz, 1H), 4.31-4.42 (m, 1H), 4.49 (dd, J=15.0, 7.5 Hz, 1H), 7.14 (d, J=8.8 Hz, 1H), 7.50 (dd, J=8.8, 2.7 Hz, 1H), 7.73 (d, J=3.1 Hz, 1H); MS (ESI+) m/z 410 (M+H)+.

Workup

  1. temperaturecooled to room temperature
  2. customquenched with saturated aqueous NaHCO3 (10 mL)
  3. extractionThe aqueous layer was extracted with ethyl acetate (3×10 mL)
  4. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-90f14143bb1849ba9248834a5af17246
Source dataset
uspto-grants-2015_11
Patent number
US09193713B2

Reaction notes

Loading…