Sodium Carbonate → HCID 44539627, compound

HRID 1695804Notes

Reaction equation

HRID 1695804 reaction equation
[CH3:1][C:2]1[S:3][CH:4]=[C:5]([C:7]([NH:9][C:10]2[C:11]3[C:15]([CH:16]=[C:17](B4OC(C)(C)CC(C)(C)O4)[CH:18]=2)=[N:14][N:13](C2CCCCO2)[CH:12]=3)=[O:8])[N:6]=1.Br[C:36]1[CH:37]=[C:38]([OH:42])[CH:39]=[CH:40][CH:41]=1.O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+]>O.O1CCOCC1.O.C(=O)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[OH:42][C:38]1[CH:37]=[C:36]([C:17]2[CH:16]=[C:15]3[C:11]([CH:12]=[N:13][NH:14]3)=[C:10]([NH:9][C:7]([C:5]3[N:6]=[C:2]([CH3:1])[S:3][CH:4]=3)=[O:8])[CH:18]=2)[CH:41]=[CH:40][CH:39]=1

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 115633-BromophenolHCID 312751,4-DioxaneHCID 582558332-Methyl-N-[2-(tetrahydro-2H-pyran-2-yl)-6-(4,4,6,6-tetramethyl-1,3,2-dioxaborinan-2-yl)-2H-indazol-4-yl]-1,3-thiazole-4-carboxamide

Product 1

HCID 44539627HCID 44539627, compoundYield 5.5%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 280Carbon DioxideSolventHCID 962WaterSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
140 °C

Procedure

2-Methyl-N-[2-(tetrahydro-2H-pyran-2-yl)-6-(4,4,6,6-tetramethyl-1,3,2-dioxaborinan-2-yl)-2H-indazol-4-yl]-1,3-thiazole-4-carboxamide (50 mg) and 3-bromophenol (18 mg) were added to a microwave vial. Pd(dppf)Cl2 (8 mg) and 1,4-dioxane (1 ml) were then added. Sodium carbonate (44 mg) in water (1 ml) was added and the reaction was heated under microwave irradiation at 140° C. for 20 min. The reaction was filtered through a 1 g silica SPE cartridge, washing with DCM:MeOH (3:1) then evaporated to dryness. The residue was dissolved in a mixture of DMSO (1.2 ml) and MeOH (0.4 ml) and purified by MDAP (method F). The product-containing fraction was left overnight then evaporated to dryness. The residue was taken up in DCM and a few drops of TFA were added before sonicating the reaction overnight. The residue was dissolved in dioxane/water (1:1, v/v, 2 ml), frozen in cardice and freeze-dried overnight to give the title compound (2 mg).

Workup

  1. filtrationThe reaction was filtered through a 1 g silica SPE cartridge
  2. washwashing with DCM:MeOH (3:1)
  3. customthen evaporated to dryness
  4. dissolutionThe residue was dissolved in a mixture of DMSO (1.2 ml) and MeOH (0.4 ml)
  5. custompurified by MDAP (method F)
  6. customthen evaporated to dryness
  7. additiona few drops of TFA were added
  8. custombefore sonicating
  9. customthe reaction overnight
  10. customfreeze-dried overnight

Sources & evidence

ORD record
ord-a2486f6323b54ac0874add5c14ace605
Source dataset
uspto-grants-2012_04
Patent number
US08163743B2

Reaction notes

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