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

HRID 1473538Notes

Reaction equation

HRID 1473538 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.[C:32]([C:34]1[CH:39]=[CH:38][C:37](B(O)O)=[C:36]([O:43][CH3:44])[CH:35]=1)#[N:33].P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>O>[C:32]([C:34]1[CH:39]=[CH:38][C:37]([C:2]2[CH:11]=[CH:10][CH:9]=[C:8]3[C:3]=2[CH:4]=[CH:5][C:6]([S:12]([NH:15][C:16]2[S:20][N:19]=[CH:18][N:17]=2)(=[O:14])=[O:13])=[CH:7]3)=[C:36]([O:43][CH3:44])[CH:35]=1)#[N:33]

Participants

6

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 532162964-Cyano-2-methoxyphenylboronic acidHCID 866873455-bromo-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide2×

Product 1

HCID 866875975-(4-cyano-2-methoxyphenyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamideYield 50%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

A vial was charged with 5-bromo-N-(4-methoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide (INTERMEDIATE D, 82.49 mg, 0.168 mmol), (4-cyano-2-methoxyphenyl)boronic acid (59.5 mg, 0.336 mmol), Pd(AmPhos)2Cl2 (5.96 mg, 8.41 μmol), potassium phosphate (107 mg, 0.505 mmol), 1,4-dioxane (631 μl), and water (210 μl). The vial was flushed with Ar (g), then sealed and heated in a Biotage Initiator microwave reactor for 30 min h at 90° C. The mixture was extracted with EtOAc (3×), and the combined organic extracts were concentrated. The residue was dissolved in DCM (1 mL) and TFA (0.5 mL). After 40 min, the mixture was diluted with MeOH and concentrated. The residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 0-50% EtOAc/Heptane) to give a light-yellow solid. The material was concentrated from DCM, and then taken up in DCM. The solvent was mostly removed via pipette, then the solid was again concentrated from DCM to give 5-(4-cyano-2-methoxyphenyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide (35.5 mg, 0.084 mmol, 50.0% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ=8.54 (d, J=1.9 Hz, 1H), 8.46 (s, 1H), 8.25 (d, J=8.3 Hz, 1H), 7.78-7.67 (m, 3H), 7.61-7.50 (m, 3H), 7.46 (d, J=7.6 Hz, 1H), 3.71 (s, 3H). m/z (ESI) 423.2 (M+H)+.

Workup

  1. customThe vial was flushed with Ar (g)
  2. customsealed
  3. extractionThe mixture was extracted with EtOAc (3×)
  4. concentrationthe combined organic extracts were concentrated
  5. dissolutionThe residue was dissolved in DCM (1 mL)
  6. additionthe mixture was diluted with MeOH
  7. concentrationconcentrated
  8. customThe residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 0-50% EtOAc/Heptane)
  9. customto give a light-yellow solid
  10. concentrationThe material was concentrated from DCM
  11. customThe solvent was mostly removed via pipette
  12. concentrationthe solid was again concentrated from DCM

Sources & evidence

ORD record
ord-49c34f9572324ae98e0e6ce893927174
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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