Sodium Hydroxide → HCID 66692266, compound

HRID 520632Notes

Reaction equation

HRID 520632 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2S(C2C=CC=CC=2)(=O)=O)=[C:4]([C:20]2[O:21][C:22]([CH2:25][N:26]3[CH2:31][CH2:30][O:29][CH:28]([CH2:32][CH3:33])[CH2:27]3)=[N:23][N:24]=2)[CH:3]=1.[CH3:34][O:35][C:36]1[C:41]([NH:42][S:43]([CH3:46])(=[O:45])=[O:44])=[CH:40][C:39](B2OC(C)(C)C(C)(C)O2)=[CH:38][N:37]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[OH-].[Na+]>O1CCOCC1.O.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH2:32]([CH:28]1[O:29][CH2:30][CH2:31][N:26]([CH2:25][C:22]2[O:21][C:20]([C:4]3[CH:3]=[C:2]([C:39]4[CH:40]=[C:41]([NH:42][S:43]([CH3:46])(=[O:44])=[O:45])[C:36]([O:35][CH3:34])=[N:37][CH:38]=4)[CH:10]=[C:9]4[C:5]=3[CH:6]=[N:7][NH:8]4)=[N:24][N:23]=2)[CH2:27]1)[CH3:33]

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 62657Potassium Phosphate, TribasicHCID 59564698N-(2-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)methanesulfonamideHCID 66776457HCID 66776457, compound

Product 1

HCID 66692266HCID 66692266, compoundYield 7.3%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

6-Bromo-4-{5-[(2-ethyl-4-morpholinyl)methyl]-1,3,4-oxadiazol-2-yl}-1-(phenylsulfonyl)-1H-indazole (170 mg, 0.319 mmol), N-[2-(methyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinyl]methanesulfonamide (115 mg, 0.351 mmol), 1,1′-bis(diphenylphosphino)ferrocene palladium dichloride (46.7 mg, 0.064 mmol) and potassium phosphate tribasic (203 mg, 0.958 mmol) were added to a microwave vial and dissolved in 1,4-dioxane (5 ml) and water (0.5 ml). The mixture was heated under microwave irradiation at 100° C. for 20 mins. The solvent was removed under a stream of nitrogen and the residue was partitioned between DCM (10 ml) and water (10 ml), separated with a hydrophobic frit and the solvent again removed under a stream of nitrogen. The protected compound was dissolved in 1,4-dioxane (1 ml) and sodium hydroxide (1 ml, 2.000 mmol) and stirred at room temperature for 4 h. The mixture was evaporated to dryness under a stream of nitrogen. The residue was partitioned between ethyl acetate (5 ml) and saturated ammonium chloride (2 ml) and separated with a hydrophilic frit. The solvent was removed under a stream of nitrogen and the crude residue was dissolved in DMSO (2 ml) and purified by Mass Directed Automated Preparative HPLC. The appropriate fraction was blown down under a stream of nitrogen to give a yellow solid. The solid was purified further by high pH MDAP (Method E) and the appropriate fraction was blown down under a stream of nitrogen to give the title compound as a white solid (12 mg).

Workup

  1. customThe solvent was removed under a stream of nitrogen
  2. customthe residue was partitioned between DCM (10 ml) and water (10 ml)
  3. customseparated with a hydrophobic frit
  4. customthe solvent again removed under a stream of nitrogen
  5. dissolutionThe protected compound was dissolved in 1,4-dioxane (1 ml)
  6. customThe mixture was evaporated to dryness under a stream of nitrogen
  7. customThe residue was partitioned between ethyl acetate (5 ml) and saturated ammonium chloride (2 ml)
  8. customseparated with a hydrophilic frit
  9. customThe solvent was removed under a stream of nitrogen
  10. dissolutionthe crude residue was dissolved in DMSO (2 ml)
  11. custompurified by Mass Directed Automated Preparative HPLC
  12. customto give a yellow solid
  13. customThe solid was purified further by high pH MDAP (Method E)

Sources & evidence

ORD record
ord-9bf5443a401e40d4a7a8bd5a912f4411
Source dataset
uspto-grants-2016_05
Patent number
US09326987B2

Reaction notes

Loading…