1,4-Dioxane → HCID 44540862, compound

HRID 1695773Notes

Reaction equation

HRID 1695773 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:17][C:18]([C:20]2[N:21]=[C:22]([CH3:25])[S:23][CH:24]=2)=[O:19])[C:5]2[C:9]([CH:10]=1)=[N:8][N:7](C1CCCCO1)[CH:6]=2.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[N:34]1[CH:39]=[CH:38][C:37](B(O)O)=[CH:36][CH:35]=1.O1CCOCC1>CO.O>[CH3:25][C:22]1[S:23][CH:24]=[C:20]([C:18]([NH:17][C:4]2[CH:3]=[C:2]([C:37]3[CH:38]=[CH:39][N:34]=[CH:35][CH:36]=3)[CH:10]=[C:9]3[C:5]=2[CH:6]=[N:7][NH:8]3)=[O:19])[N:21]=1

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 2734379(Pyridin-4-yl)boronic acid2×HCID 58255778N-[6-bromo-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-yl]-2-methyl-1,3-thiazole-4-carboxamide

Product 1

HCID 44540862HCID 44540862, compoundYield 47.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A microwave vial was charged with N-[6-bromo-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-yl]-2-methyl-1,3-thiazole-4-carboxamide (50 mg), Solvias catalyst (7 mg), tripotassium phosphate (76 mg), 4-pyridinylboronic acid (15 mg), 1,4-dioxane (0.5 ml) and water (0.1 ml). The mixture was heated under microwave irradiation for a total of 60 min at 80° C. 4-Pyridinylboronic acid (15 mg) was added and the mixture was heated for 30 min at 80° C., then 30 min at 120° C. The reaction mixture was passed through a silica cartridge preconditioned with methanol, washing with methanol, then dried in vacuo. The residue was extracted with DCM/water, dried through a hydrophobic frit and dried in vacuo. The residue was dissolved in DMSO:methanol (1 ml, 1:1, v/v) and purified by MDAP (method E). Appropriate fractions were dried under a stream of nitrogen. The residue was dissolved in methanol and a few drops of 2M HCl (aq) were added and the reaction was stirred for 30 min. The reaction mixture was passed through an aminopropyl cartridge, preconditioned with methanol, washing with methanol, then dried to give title compound, (19 mg).

Workup

  1. temperaturethe mixture was heated for 30 min at 80° C.
  2. custom30 min
  3. customat 120° C
  4. washwashing with methanol
  5. customdried in vacuo
  6. extractionThe residue was extracted with DCM/water
  7. customdried through a hydrophobic frit
  8. customdried in vacuo
  9. dissolutionThe residue was dissolved in DMSO
  10. custommethanol (1 ml, 1:1, v/v) and purified by MDAP (method E)
  11. customAppropriate fractions were dried under a stream of nitrogen
  12. dissolutionThe residue was dissolved in methanol
  13. additiona few drops of 2M HCl (aq) were added
  14. washwashing with methanol
  15. customdried

Sources & evidence

ORD record
ord-ccb0541508c74f8bb7687c659ab71cc2
Source dataset
uspto-grants-2012_04
Patent number
US08163743B2

Reaction notes

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