Water → 5-(3-fluoro-4-(morpholinomethyl)phenyl)-3-(1-isopropyl-1H-1,2,3-triazol-4-yl)pyridin-2-amine

HRID 1053133Notes

Reaction equation

HRID 1053133 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:30]=[C:29](B2OC(C)(C)C(C)(C)O2)[CH:28]=[CH:27][C:19]=1[CH2:20][N:21]1[CH2:26][CH2:25][O:24][CH2:23][CH2:22]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>[F:17][C:18]1[CH:30]=[C:29]([C:2]2[CH:3]=[C:4]([C:9]3[N:10]=[N:11][N:12]([CH:14]([CH3:16])[CH3:15])[CH:13]=3)[C:5]([NH2:8])=[N:6][CH:7]=2)[CH:28]=[CH:27][C:19]=1[CH2:20][N:21]1[CH2:22][CH2:23][O:24][CH2:25][CH2:26]1

Participants

8

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 438110633-Fluoro-4-(N-morpholinomethyl)phenylboronic acid, pinacol esterHCID 902731555-bromo-3-(1-isopropyl-1H-[1,2,3]triazol-4-yl)-pyridin-2-ylamine

Product 1

HCID 771061635-(3-fluoro-4-(morpholinomethyl)phenyl)-3-(1-isopropyl-1H-1,2,3-triazol-4-yl)pyridin-2-amineYield 36%

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-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)morpholine (250 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, 0.03 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. The crude compound was purified by column using 100-200 mesh silica gel. The column was eluted with 80% EtOAc in hexanes to afford 100 mg (yield: 35.71%) 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. customThe crude compound was purified by column
  8. washThe column was eluted with 80% EtOAc in hexanes

Sources & evidence

ORD record
ord-d9f53d9cd95847929ffc799a2f921dfb
Source dataset
uspto-grants-2016_07
Patent number
US09393248B1

Reaction notes

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