1,4-Dioxane → HCID 86687546, compound

HRID 1473491Notes

Reaction equation

HRID 1473491 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1B(O)O.Br[C:13]1[C:22]2[C:17](=[CH:18][C:19]([S:23]([N:26](CC3C=CC(OC)=CC=3)[C:27]3[S:28][CH:29]=[CH:30][N:31]=3)(=[O:25])=[O:24])=[CH:20][CH:21]=2)[CH:16]=[N:15][CH:14]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>C(C1C(C(C)(C)C)=C([Pd]Cl)C=CC=1NC)(C)(C)C.O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:13]1[C:22]2[C:17](=[CH:18][C:19]([S:23]([NH:26][C:27]3[S:28][CH:29]=[CH:30][N:31]=3)(=[O:25])=[O:24])=[CH:20][CH:21]=2)[CH:16]=[N:15][CH:14]=1

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 27339582-Methoxyphenylboronic acidHCID 86687470HCID 86687470, compound

Product 1

HCID 86687546HCID 86687546, compoundYield 66%

Reagents, catalysts & solvents 2

HCID 178482226HCID 178482226, compoundCatalystHCID 962WaterSolvent

Procedure

To a microwave vial charged with (2-methoxyphenyl)boronic acid (25.6 mg, 0.168 mmol), 4-bromo-N-(4-methoxybenzyl)-N-(thiazol-2-yl)isoquinoline-7-sulfonamide (Intermediate PPPP) (75 mg, 0.153 mmol), and potassium phosphate tribasic (38.0 μl, 0.459 mmol) was added dioxane (613 μl) and water (204 μl). The mixture was purged with argon prior to the addition of 1,1-bis[(di-t-butyl-p-methylaminophenyl]palladium(II) chloride (10.83 mg, 0.015 mmol). The mixture was irradiated at 100° C. in a microwave for 30 min. The organics were decanted, the aqueous rinsed with EtOAc and the organics combined and dried under reduced pressure. The crude material was dissolved in DCM (1.5 ml) and TFA (0.5 ml) was added and the mixture shaken at room temperature for 2 hrs. The resulting mixture was dried under reduced pressure and purified with a 25 g Interchim HP spherical silica column (Interchim, Mouintlucon, France) (15 μm) ramping EtOAc in heptane (0 to 100%, 10% DCM throughout) with product eluting at 100% polar eluent to afford 4-(2-methoxyphenyl)-N-(thiazol-2-yl)isoquinoline-7-sulfonamide (40 mg, 0.101 mmol, 65.8% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 6.87 (d, J=4.60 Hz, 1H) 7.08-7.16 (m, 1H) 7.22 (d, J=8.22 Hz, 1H) 7.25-7.35 (m, 2H) 7.48-7.55 (m, 1H) 7.61 (d, J=8.90 Hz, 1H) 8.00 (dd, J=8.85, 1.91 Hz, 1H) 8.48 (s, 1H) 8.71 (d, J=1.76 Hz, 1H) 9.55 (s, 1H) 12.87 (br. s., 1H). m/z (ESI) 398.2 (M+H)+.

Workup

  1. customThe mixture was purged with argon
  2. customThe mixture was irradiated at 100° C. in a microwave for 30 min
  3. customThe organics were decanted
  4. washthe aqueous rinsed with EtOAc
  5. customdried under reduced pressure
  6. dissolutionThe crude material was dissolved in DCM (1.5 ml)
  7. additionTFA (0.5 ml) was added
  8. customThe resulting mixture was dried under reduced pressure
  9. custompurified with a 25 g Interchim HP spherical silica column (Interchim, Mouintlucon, France) (15 μm)
  10. washeluting at 100% polar eluent

Sources & evidence

ORD record
ord-75b12d21fe5d4042b945ee4347035eb2
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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