Potassium Phosphate, Tribasic → 4-(5-(6-(1-methylethoxy)-2-pyrazinyl)-1H-indol-3-yl)-2-pyridinamine

HRID 1529324Notes

Reaction equation

HRID 1529324 reaction equation
I[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[CH:16]=[N:15][CH:14]=[C:13]([O:17][CH:18]([CH3:20])[CH3:19])[N:12]=3)[CH:9]=2)[N:4](S(C2C=CC(C)=CC=2)(=O)=O)[CH:3]=1.CC1(C)C(C)(C)OB([C:39]2[CH:44]=[CH:43][N:42]=[C:41]([NH2:45])[CH:40]=2)O1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1.O>[CH3:20][CH:18]([O:17][C:13]1[N:12]=[C:11]([C:8]2[CH:9]=[C:10]3[C:5](=[CH:6][CH:7]=2)[NH:4][CH:3]=[C:2]3[C:39]2[CH:44]=[CH:43][N:42]=[C:41]([NH2:45])[CH:40]=2)[CH:16]=[N:15][CH:14]=1)[CH3:19]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 457857074-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amineHCID 679596923-iodo-5-(6-isopropoxypyrazin-2-yl)-1-tosyl-1H-indole

Product 1

HCID 679600154-(5-(6-(1-methylethoxy)-2-pyrazinyl)-1H-indol-3-yl)-2-pyridinamine

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
130 °C

Procedure

A solution of 3-iodo-5-(6-isopropoxypyrazin-2-yl)-1-tosyl-1H-indole (0.060 g, 0.11 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (39, 0.17 mmol), Potassium Phosphate (0.072 g, 0.34 mmol), Pd2 dba3 (5 mg, 6 μmol), X-Phos (5 mg, 0.011 mmol), and dioxane/water (2/1, 1.5 mL) was heated in a microwave at 125° C. for 10 min. The solution was cooled, the aqueous layer was removed, and the organic layer was purified by prep HPLC (66-95% ACN/water/0.1% TFA). The resulting product was dissolved in dioxane (1 mL), 1M NaOH (0.2 mL) was added, and the mixture was heated in a microwave at 130° C. for 10 min. The resulting solution was purified by preparative HPLC (10-90% ACN/water/0.1% TFA) to give 4-(5-(6-(1-methylethoxy)-2-pyrazinyl)-1H-indol-3-yl)-2-pyridinamine. MS (ESI, pos. ion) m/z: 346 (M+1).

Workup

  1. temperatureThe solution was cooled
  2. customthe aqueous layer was removed
  3. customthe organic layer was purified by prep HPLC (66-95% ACN/water/0.1% TFA)
  4. dissolutionThe resulting product was dissolved in dioxane (1 mL)
  5. addition1M NaOH (0.2 mL) was added
  6. customThe resulting solution was purified by preparative HPLC (10-90% ACN/water/0.1% TFA)

Sources & evidence

ORD record
ord-d198d7fb93a24e7a8a5cfa0a732a9f4c
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

Loading…