Sodium Carbonate → 2-Methyl-N-[6-(2-oxo-2,3-dihydro-1H-indol-4-yl)-1H-indazol-4-yl]-1,3-thiazole-4-carboxamide

HRID 520650Notes

Reaction equation

HRID 520650 reaction equation
Br[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5](Cl)[NH:6]2.[CH3:12][C:13]1[S:14][CH:15]=[C:16]([C:18]([NH:20][C:21]2[C:22]3[C:26]([CH:27]=[C:28](B4OC(C)(C)CC(C)(C)O4)[CH:29]=2)=[N:25][N:24](C2CCCCO2)[CH:23]=3)=[O:19])[N:17]=1.C(=O)([O-])[O-:47].[Na+].[Na+].O1CCOCC1>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].O>[CH3:12][C:13]1[S:14][CH:15]=[C:16]([C:18]([NH:20][C:21]2[CH:29]=[C:28]([C:2]3[CH:10]=[CH:9][CH:8]=[C:7]4[C:3]=3[CH2:4][C:5](=[O:47])[NH:6]4)[CH:27]=[C:26]3[C:22]=2[CH:23]=[N:24][NH:25]3)=[O:19])[N:17]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 197003094-bromo-2-chloro-1H-indoleHCID 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 532332132-Methyl-N-[6-(2-oxo-2,3-dihydro-1H-indol-4-yl)-1H-indazol-4-yl]-1,3-thiazole-4-carboxamide

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Conditions

Temperature
140 °C

Procedure

4-Bromo-2-chloro-1H-indole (24 mg), 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), Pd(dppf)Cl2 (8 mg) and sodium carbonate (44 mg) were added to a microwave vial. 1,4-Dioxane (0.5 ml) and water (0.5 ml) were added and the reaction was heated in the microwave at 140° C. for 20 min. The reaction was passed through a 1 g silica cartridge washing with DCM:methanol. The solvent was evaporated in the blow down. The residue was dissolved in DMSO:methanol (1.6 ml, 1:1, v/v), passed through a C18 cartridge (1 g) washing with acetonitrile and evaporated in the blow down. The residue was dissolved in DMSO:methanol (1.6 ml, 1:1, v/v) and purified by MDAP (method M). The pure fraction was evaporated to dryness to give title compound, 8 mg.

Workup

  1. washwashing with DCM
  2. customThe solvent was evaporated in the blow down
  3. dissolutionThe residue was dissolved in DMSO
  4. washwashing with acetonitrile
  5. customevaporated in the blow down
  6. dissolutionThe residue was dissolved in DMSO
  7. custommethanol (1.6 ml, 1:1, v/v) and purified by MDAP (method M)
  8. customThe pure fraction was evaporated to dryness

Sources & evidence

ORD record
ord-4a0e8f73252242b0b3255c51df8f760e
Source dataset
uspto-grants-2016_05
Patent number
US09326987B2

Reaction notes

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