5-Amino-1,2,4-thiadiazole → HCID 117737009, compound

HRID 1504544Notes

Reaction equation

HRID 1504544 reaction equation
[CH3:1][O:2][CH:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[N:9]1[C:18]2[C:13](=[CH:14][C:15]([S:19](OC3C(F)=C(F)C(F)=C(F)C=3F)(=[O:21])=[O:20])=[CH:16][CH:17]=2)[CH:12]=[CH:11][C:10]1=[O:34].[NH2:35][C:36]1[S:40][N:39]=[CH:38][N:37]=1>CCOC(C)=O>[CH3:1][O:2][C@H:3]1[CH2:8][CH2:7][CH2:6][CH2:5][C@@H:4]1[N:9]1[C:18]2[C:13](=[CH:14][C:15]([S:19]([NH:35][C:36]3[S:40][N:39]=[CH:38][N:37]=3)(=[O:21])=[O:20])=[CH:16][CH:17]=2)[CH:12]=[CH:11][C:10]1=[O:34]

Participants

4

Reactant 2

HCID 2902745-Amino-1,2,4-thiadiazoleHCID 117736959HCID 117736959, compound

Product 1

HCID 117737009HCID 117737009, compoundYield 38.8%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A 10-mL RBF was charged with (±)-perfluorophenyl 1-(2-methoxycyclohexyl)-2-oxo-1,2-dihydroquinoline-6-sulfonate (65 mg, 0.129 mmol), 5-amino-1,2,4-thiadiazole (19.6 mg, 0.194 mmol) then purged with nitrogen for 10 min. Tetrahydrofuran (323 μL) and dimethyl sulfoxide (990 μL) were sequentially introduced via syringe and the resultant solution cooled to 0° C. A solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (1.0 M, (871 μL, 0.871 mmol) was added dropwise via syringe to the stirred reaction mixture over 3 min. After 15 min, 1.0 N HCl (5 mL) was introduced and the resultant reaction mixture was allowed to warm to ambient temperature. The mixture was diluted with and EtOAc (10 mL) and the layers were separated, and the aqueous layer was further extracted with EtOAc (3×10 mL). The combined organic layers were then washed with brine (20 mL), dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure. The residue was dissolved in DMSO (2 mL), filtered through a 0.2 micron filter, and purified by reverse-phase HPLC (Waters XBridge Prep Shield RP18 10 μm OBD 19×100 mm) gradient, 20 to 75% MeCN in water (containing 0.1% trifluoroacetic acid as an additive), flow rate 40 mL/min to afford 1-((1S,2S)-2-methoxycyclohexyl)-2-oxo-N-1,2,4-thiadiazol-5-yl-1,2-dihydro-6-quinolinesulfonamide (21 mg, 0.050 mmol, 38.7% yield, mixture of enantiomers) as a white solid. 1 H NMR (500 MHz, DMSO-d6) δ ppm 8.44 (s, 1 H) 8.20 (s, 1 H) 8.04 (d, J=9.54 Hz, 1H) 7.90-7.96 (m, 1 H) 7.84-7.90 (m, 1 H) 6.61 (d, J=9.47 Hz, 1 H) 4.41 (br. s., 2 H) 3.03 (s, 3 H) 2.90 (br. s., 1 H) 2.22 (d, J=11.48 Hz, 1 H) 1.61-1.85 (m, 3 H) 1.38-1.57 (m, 1 H) 1.07-1.37 (m, 2 H). m/z (ESI) 421.2 (M+H)+.

Workup

  1. customthen purged with nitrogen for 10 min
  2. additionTetrahydrofuran (323 μL) and dimethyl sulfoxide (990 μL) were sequentially introduced via syringe
  3. additionA solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (1.0 M, (871 μL, 0.871 mmol) was added dropwise via syringe to the stirred reaction mixture over 3 min
  4. addition1.0 N HCl (5 mL) was introduced
  5. customthe resultant reaction mixture
  6. temperatureto warm to ambient temperature
  7. customthe layers were separated
  8. extractionthe aqueous layer was further extracted with EtOAc (3×10 mL)
  9. washThe combined organic layers were then washed with brine (20 mL)
  10. dry with materialdried over anhydrous magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. dissolutionThe residue was dissolved in DMSO (2 mL)
  14. filtrationfiltered through a 0.2 micron
  15. filtrationfilter
  16. custompurified by reverse-phase HPLC (Waters XBridge Prep Shield RP18 10 μm OBD 19×100 mm) gradient, 20 to 75% MeCN in water (
  17. additioncontaining 0.1% trifluoroacetic acid as an additive), flow rate 40 mL/min

Sources & evidence

ORD record
ord-59cf0fdb183d4670a6a9905f2070e55e
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

Loading…