Water → [5-[6-Amino-5-(1-isopropyltriazol-4-yl)-3-pyridyl]-2-fluoro-phenyl]-morpholino-methanone

HRID 1053118Notes

Reaction equation

HRID 1053118 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:9]2[N:10]=[N:11][N:12]([CH:14]([CH3:16])[CH3:15])[CH:13]=2)[C:5]([NH2:8])=[N:6][CH:7]=1.[F:17][C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][C:19]=1[C:27]([N:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1)=[O:28].O.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.CCOC(C)=O.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>[NH2:8][C:5]1[N:6]=[CH:7][C:2]([C:21]2[CH:22]=[CH:23][C:18]([F:17])=[C:19]([C:27]([N:29]3[CH2:30][CH2:31][O:32][CH2:33][CH2:34]3)=[O:28])[CH:20]=2)=[CH:3][C:4]=1[C:9]1[N:10]=[N:11][N:12]([CH:14]([CH3:16])[CH3:15])[CH:13]=1

Participants

8

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 44717532B-[4-Fluoro-3-(4-morpholinylcarbonyl)phenyl]boronic acidHCID 902731555-bromo-3-(1-isopropyl-1H-[1,2,3]triazol-4-yl)-pyridin-2-ylamine

Product 1

HCID 90273335[5-[6-Amino-5-(1-isopropyltriazol-4-yl)-3-pyridyl]-2-fluoro-phenyl]-morpholino-methanoneYield 73.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 5-bromo-3-(1-isopropyl-1H-[1,2,3]triazol-4-yl)-pyridin-2-ylamine (200 mg, 0.70 mmol) and (4-fluoro-3-(morpholine-4-carbonyl)phenyl)boronic acid (197 mg, 0.77 mmol) in 1,4-dioxane (10.0 mL)/water (5.0 mL) was added Cs2CO3 (690 mg, 2.12 mmol) at room temperature. The reaction mixture was degassed with argon for 30 min. Then Pd(PPh3)4 (40 mg, 0.035 mmol) was added and allowed to stir at 110° C. for 30 min in CEM micro wave. 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 (20 mL), dried over anhydrous Na2SO4 and solvent was evaporated under reduced pressure. Crude compound was purified by column using 100-200 mesh silica gel. The column was eluted with 5% MeOH in DCM to afford 210 mg (yield: 72.41%) of title compound as pale yellow solid.

Workup

  1. customThe reaction mixture was degassed with argon for 30 min
  2. temperatureThe reaction mixture was cooled to RT
  3. washwashed with water (50 mL)
  4. washThe organic layer was washed with brine solution (20 mL)
  5. dry with materialdried over anhydrous Na2SO4 and solvent
  6. customwas evaporated under reduced pressure
  7. customCrude compound was purified by column
  8. washThe column was eluted with 5% MeOH in DCM

Sources & evidence

ORD record
ord-ac443f2362dd4010872114a7f77c6027
Source dataset
uspto-grants-2016_07
Patent number
US09393248B1

Reaction notes

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