Potassium Carbonate → HCID 44540398, compound

HRID 1695770Notes

Reaction equation

HRID 1695770 reaction equation
[CH3:1][S:2]([C:5]1[CH:6]=[C:7](B(O)O)[CH:8]=[N:9][CH:10]=1)(=[O:4])=[O:3].Br[C:15]1[CH:23]=[C:22]2[C:18]([CH:19]=[N:20][NH:21]2)=[C:17]([NH:24][C:25]([C:27]2[N:28]=[C:29]([CH3:32])[S:30][CH:31]=2)=[O:26])[CH:16]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.CO.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]>[CH3:32][C:29]1[S:30][CH:31]=[C:27]([C:25]([NH:24][C:17]2[CH:16]=[C:15]([C:7]3[CH:8]=[N:9][CH:10]=[C:5]([S:2]([CH3:1])(=[O:4])=[O:3])[CH:6]=3)[CH:23]=[C:22]3[C:18]=2[CH:19]=[N:20][NH:21]3)=[O:26])[N:28]=1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 441193815-(Methylsulphonyl)pyridine-3-boronic acidHCID 58255750N-(6-bromo-1H-indazol-4-yl)-2-methyl-1,3-thiazole-4-carboxamide

Product 1

HCID 44540398HCID 44540398, compoundYield 5.8%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
150 °C

Procedure

To a solution of 5-(methylsulfonyl)-3-pyridinylboronic acid (24 mg, 0.12 mmol, available from Combi-Blocks Inc.) in 1,4-dioxane (1 ml) was added a solution of N-(6-bromo-1H-indazol-4-yl)-2-methyl-1,3-thiazole-4-carboxamide (34 mg, 0.10 mmol), also in 1,4-dioxane (1 ml). A solution of potassium carbonate (17 mg, 0.12 mmol) in water (0.2 ml) was then added, followed by Pd(dppf)Cl2 (10 mg). The reaction vessel was sealed and heated in CEM Discover at 150° C. for 30 min. The mixture was cooled and the solvent was evaporated in vacuo using the Genevac to give the crude products. The sample was loaded in methanol and applied to reverse phase (C18) cartridge (500 mg) and eluted using MeCN/TFA 0.1% (3×3 ml). The appropriate fractions were combined and dried under a stream of nitrogen then the residue was dissolved in (3:1, DMSO:MeOH, 0.5 ml) and purified by MDAP (Method C) to afford the title compound, (2.4 mg).

Workup

  1. customThe reaction vessel was sealed
  2. temperatureThe mixture was cooled
  3. customthe solvent was evaporated in vacuo
  4. customto give the crude products
  5. washeluted
  6. customdried under a stream of nitrogen
  7. dissolutionthe residue was dissolved in (3:1, DMSO:MeOH, 0.5 ml)
  8. custompurified by MDAP (Method C)

Sources & evidence

ORD record
ord-a635454c12ca4fb7ae92dbac1c21ae88
Source dataset
uspto-grants-2012_04
Patent number
US08163743B2

Reaction notes

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