Water → (4-(6-amino-5-(1-isopropyl-1H-1,2,3-triazol-4-yl)pyridin-3-yl)-2-fluorophenyl)(morpholino)methanone

HRID 1053134Notes

Reaction equation

HRID 1053134 reaction equation
[F:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][C:7]=1[C:8]([N:10]1[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1)=[O:9].Br[C:20]1[CH:21]=[C:22]([C:27]2[N:28]=[N:29][N:30]([CH:32]([CH3:34])[CH3:33])[CH:31]=2)[C:23]([NH2:26])=[N:24][CH:25]=1.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>[NH2:26][C:23]1[N:24]=[CH:25][C:20]([C:4]2[CH:5]=[CH:6][C:7]([C:8]([N:10]3[CH2:15][CH2:14][O:13][CH2:12][CH2:11]3)=[O:9])=[C:2]([F:1])[CH:3]=2)=[CH:21][C:22]=1[C:27]1[N:28]=[N:29][N:30]([CH:32]([CH3:34])[CH3:33])[CH:31]=1

Participants

8

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 576184153-Fluoro-4-(morpholine-4-carbonyl)phenylboronic acidHCID 902731555-bromo-3-(1-isopropyl-1H-[1,2,3]triazol-4-yl)-pyridin-2-ylamine

Product 1

HCID 77106164(4-(6-amino-5-(1-isopropyl-1H-1,2,3-triazol-4-yl)pyridin-3-yl)-2-fluorophenyl)(morpholino)methanoneYield 34.43%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
120 °C

Procedure

To a solution of (3-fluoro-4-(morpholine-4-carbonyl)phenyl)boronic acid (269 mg, 1.06 mmol) and of 5-bromo-3-(1-isopropyl-1H-[1,2,3]triazol-4-yl)-pyridin-2-ylamine (250 mg, 0.886 mmol) in 1,4-dioxane (10.0 mL)/water (5.0 mL) was added Cs2CO3 (863 mg, 2.65 mmol) at room temperature. The reaction mixture was degassed with argon for 30 min. Then Pd(PPh3)4 (51 mg, 0.04 mmol) was added and allowed to stir at 120° 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 to afford crude compound. Crude compound was purified by column using 100-200 mesh silica gel. The column was eluted with 5% MeOH in DCM to afford 125 mg (yield: 34.43%) of the 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. customto afford crude compound
  8. customCrude compound was purified by column
  9. washThe column was eluted with 5% MeOH in DCM

Sources & evidence

ORD record
ord-536539d8c31d499fa8e306cf397b7349
Source dataset
uspto-grants-2016_07
Patent number
US09393248B1

Reaction notes

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