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

HRID 632488Notes

Reaction equation

HRID 632488 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 947NitrogenHCID 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. 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. customto afford crude compound (GVK-B1319-120A1)
  10. customCrude compound was purified by column
  11. washeluted with 2-3% MeOH in DCM

Sources & evidence

ORD record
ord-0b092471a201464698e5d72aeba94a56
Source dataset
uspto-grants-2016_04
Patent number
US09321748B2

Reaction notes

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