Nitrogen → 3-(1-Isopropyl-1H-1,2,3-triazol-4-yl)-5-(4-(2-morpholinoethyl)phenyl)pyridin-2-amine

HRID 1053132Notes

Reaction equation

HRID 1053132 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[CH:11][CH:10]=2)O1.Br[C:25]1[CH:26]=[C:27]([C:32]2[N:33]=[N:34][N:35]([CH:37]([CH3:39])[CH3:38])[CH:36]=2)[C:28]([NH2:31])=[N:29][CH:30]=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>[CH:37]([N:35]1[CH:36]=[C:32]([C:27]2[C:28]([NH2:31])=[N:29][CH:30]=[C:25]([C:9]3[CH:10]=[CH:11][C:12]([CH2:15][CH2:16][N:17]4[CH2:18][CH2:19][O:20][CH2:21][CH2:22]4)=[CH:13][CH:14]=3)[CH:26]=2)[N:33]=[N:34]1)([CH3:39])[CH3:38]

Participants

8

Reactant 4

HCID 947Nitrogen2×HCID 10796Cesium carbonateHCID 44392864-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenethyl)morpholineHCID 902731555-bromo-3-(1-isopropyl-1H-[1,2,3]triazol-4-yl)-pyridin-2-ylamine

Product 1

HCID 771061623-(1-Isopropyl-1H-1,2,3-triazol-4-yl)-5-(4-(2-morpholinoethyl)phenyl)pyridin-2-amineYield 53.4%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

To a solution of 4-{2-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-ethyl}-morpholine (can be prepared as described in US2002026052) (101 mg, 0.31 mmol) and 5-bromo-3-(1-isopropyl-1H-[1,2,3]triazol-4-yl)-pyridin-2-ylamine (90 mg, 0.31 mmol) in 1,4-dioxane (7.0 mL)/water (3.0 mL) was added Cs2CO3 (251 mg, 0.70 mmol) at RT. N2 was purged through the reaction mixture for 10 min Pd(PPh3)4 (18 mg, 0.015 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 to afford crude compound (GVK-B1319-120A1). Crude compound was purified by column using 100-200 mesh silica gel and eluted with 2-3% MeOH in DCM to afford 65 mg of a brown semisolid. Further purification of Prep-HPLC furnished 14 mg of the title compound as an off-white solid.

Workup

  1. customwas purged for 10 min
  2. temperatureThe reaction mixture was cooled to RT
  3. additiondiluted with EtOAc (50 mL)
  4. washwashed with water (50 mL)
  5. washThe organic layer was washed with brine solution (50 mL)
  6. dry with materialdried over anhydrous Na2SO4 and solvent
  7. customwas evaporated under reduced pressure
  8. customto afford crude compound (GVK-B1319-120A1)
  9. customCrude compound was purified by column
  10. washeluted with 2-3% MeOH in DCM

Sources & evidence

ORD record
ord-38d834ae24c9468b9f2dceaf01aff94c
Source dataset
uspto-grants-2016_07
Patent number
US09393248B1

Reaction notes

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