Nitrogen → HCID 77106758, compound

HRID 632502Notes

Reaction equation

HRID 632502 reaction equation
[N:1]1([C:7](=[O:24])[CH2:8][C:9]2[CH:14]=[CH:13][C:12](B3OC(C)(C)C(C)(C)O3)=[CH:11][CH:10]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[C:26]1[CH:27]=[C:28]([C:33]2[N:34]=[N:35][N:36]([CH:38]([CH3:40])[CH3:39])[CH:37]=2)[C:29]([NH2:32])=[N:30][CH:31]=1.C([O-])([O-])=O.[Cs+].[Cs+].N#N>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[NH2:32][C:29]1[N:30]=[CH:31][C:26]([C:12]2[CH:11]=[CH:10][C:9]([CH2:8][C:7]([N:1]3[CH2:2][CH2:3][O:4][CH2:5][CH2:6]3)=[O:24])=[CH:14][CH:13]=2)=[CH:27][C:28]=1[C:33]1[N:34]=[N:35][N:36]([CH:38]([CH3:40])[CH3:39])[CH:37]=1

Participants

8

Reactant 4

HCID 947NitrogenHCID 10796Cesium carbonateHCID 593926601-Morpholino-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethanoneHCID 902731555-bromo-3-(1-isopropyl-1H-[1,2,3]triazol-4-yl)-pyridin-2-ylamine

Product 1

HCID 77106758HCID 77106758, compoundYield 28.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 1-Morpholin-4-yl-2-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-ethanone (129 mg, 0.39 mmol) and 5-bromo-3-(1-isopropyl-1H-[1,2,3]triazol-4-yl)-pyridin-2-ylamine (100 mg, 0.35 mmol) in 1,4-dioxane (6.0 mL)/water (4.0 mL) was added Cs2CO3 (284 mg, 0.87 mmol) at room temperature. N2 was purged through the reaction mixture for 10 min. Pd(PPh3)4 (20 mg, 0.017 mmol) was added and through the reaction mixture N2 was purged for 10 min and stirred at 100° C. for 16 h. The reaction mixture was cooled to RT, diluted with EtOAc (50 mL) and washed with water (50 mL). The organic layer was washed with brine solution (50 mL), dried over anhydrous Na2SO4 and solvent was evaporated under reduced pressure. Crude compound was purified by column chromatography using 100-200 mesh silica gel and eluted with 2-3% MeOH in DCM to afford 40 mg (yield: 27.7%) of the title compound as brown semisolid. Product was converted to its HCl salt by using 2M HCl in ether to afford 42 mg of an off-white solid.

Workup

  1. customN2 was purged through the reaction mixture for 10 min
  2. customwas purged for 10 min
  3. temperatureThe reaction mixture was cooled to RT
  4. additiondiluted with EtOAc (50 mL)
  5. washwashed with water (50 mL)
  6. washThe organic layer was washed with brine solution (50 mL)
  7. dry with materialdried over anhydrous Na2SO4 and solvent
  8. customwas evaporated under reduced pressure
  9. customCrude compound was purified by column chromatography
  10. washeluted with 2-3% MeOH in DCM

Sources & evidence

ORD record
ord-b99481ef442c421f9145990cde93ea30
Source dataset
uspto-grants-2016_04
Patent number
US09321748B2

Reaction notes

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