1,4-Dioxane → 5-(2-methoxyphenyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide

HRID 1473422Notes

Reaction equation

HRID 1473422 reaction equation
Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([S:12]([N:15](CC1C=CC(OC)=CC=1OC)[C:16]1[S:20][N:19]=[CH:18][N:17]=1)(=[O:14])=[O:13])=[CH:7]2.[CH3:32][O:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1B(O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>O>[CH3:32][O:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([S:12]([NH:15][C:16]1[S:20][N:19]=[CH:18][N:17]=1)(=[O:14])=[O:13])=[CH:7]2

Participants

6

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 27339582-Methoxyphenylboronic acidHCID 866873455-bromo-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide2×

Product 1

HCID 715865115-(2-methoxyphenyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamideYield 74%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
100 °C

Procedure

A vial was charged with 5-bromo-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide (INTERMEDIATE D) (73.69 mg, 0.142 mmol), 2-methoxyphenylboronic acid (43.0 mg, 0.283 mmol), Pd(AmPhos)2Cl2 (5.01 mg, 7.08 μmol), potassium phosphate (90 mg, 0.425 mmol), 1,4-dioxane (708 μl), and water (236 μl). The vial was sealed and heated in a microwave reactor for 30 min at 100° C. The mixture was diluted with water and extracted with EtOAc (3×). The combined organic extracts were concentrated. The residue was dissolved in DCM (1 mL) and TFA (0.5 mL). After 2 h, the mixture was diluted with MeOH and filtered through diatomaceous earth with the aid of DCM. The filtrate was concentrated. The residue was purified twice by chromatography on silica gel (12-g columns, first with 0 to 5% MeOH/DCM, then with 2.5% MeOH/DCM), and the resulting material was dissolved in DCM and loaded onto a 1-g PE-AX ion exchange column (Biotage AB, Uppsala, Sweden). The column was flushed with 1:1 MeOH/DCM, then eluted with 10% HCl/MeOH (made by dissolving 1 mL on conc. HCl in 9 mL of MeOH). The acidic fraction was concentrated to give 5-(2-methoxyphenyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide (41.62 mg, 0.105 mmol, 74.0% yield) as an off-white solid: 1H NMR (400 MHz, DMSO-d6) δ ppm=8.59-8.44 (m, 2H), 8.20 (d, J=8.2 Hz, 1H), 7.77-7.66 (m, 2H), 7.58 (d, J=8.9 Hz, 1H), 7.54-7.45 (m, 2H), 7.26-7.16 (m, 2H), 7.13-7.05 (m, 1H), 3.63 (s, 3H); m/z (ESI) 398.2 (M+H)+.

Workup

  1. customThe vial was sealed
  2. extractionextracted with EtOAc (3×)
  3. concentrationThe combined organic extracts were concentrated
  4. dissolutionThe residue was dissolved in DCM (1 mL)
  5. additionthe mixture was diluted with MeOH
  6. filtrationfiltered through diatomaceous earth with the aid of DCM
  7. concentrationThe filtrate was concentrated
  8. customThe residue was purified twice by chromatography on silica gel (12-g columns
  9. dissolutionfirst with 0 to 5% MeOH/DCM, then with 2.5% MeOH/DCM), and the resulting material was dissolved in DCM
  10. customThe column was flushed with 1:1 MeOH/DCM
  11. washeluted with 10% HCl/MeOH (made by dissolving 1 mL on conc. HCl in 9 mL of MeOH)
  12. concentrationThe acidic fraction was concentrated

Sources & evidence

ORD record
ord-a310dfd6900745c38ba1f566b5438507
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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