Cesium carbonate → 3-(1-Isopropyltriazol-4-yl)-5-[3-(morpholinomethyl)phenyl]pyridin-2-amine

HRID 1053141Notes

Reaction equation

HRID 1053141 reaction equation
C([O-])([O-])=O.[Cs+].[Cs+].[O:7]1[CH2:12][CH2:11][N:10]([CH2:13][C:14]2[CH:15]=[C:16](B(O)O)[CH:17]=[CH:18][CH:19]=2)[CH2:9][CH2:8]1.Br[C:24]1[CH:25]=[C:26]([C:31]2[N:32]=[N:33][N:34]([CH:36]([CH3:38])[CH3:37])[CH:35]=2)[C:27]([NH2:30])=[N:28][CH:29]=1>O1CCOCC1.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>[CH:36]([N:34]1[CH:35]=[C:31]([C:26]2[C:27]([NH2:30])=[N:28][CH:29]=[C:24]([C:16]3[CH:17]=[CH:18][CH:19]=[C:14]([CH2:13][N:10]4[CH2:11][CH2:12][O:7][CH2:8][CH2:9]4)[CH:15]=3)[CH:25]=2)[N:32]=[N:33]1)([CH3:38])[CH3:37]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 110314093-(Morpholinomethyl)phenylboronic acidHCID 902731555-bromo-3-(1-isopropyl-1H-[1,2,3]triazol-4-yl)-pyridin-2-ylamine

Product 1

HCID 771065593-(1-Isopropyltriazol-4-yl)-5-[3-(morpholinomethyl)phenyl]pyridin-2-amineYield 58.5%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
120 °C

Procedure

Cs2CO3 (858 mg, 2.64 mmol) was added to a solution of (3-(morpholinomethyl)phenyl)boronic acid (250 mg, 0.88 mmol) and 5-bromo-3-(1-isopropyl-1H-[1,2,3]triazol-4-yl)-pyridin-2-ylamine (215 mg, 0.97 mmol) in dioxane: water (8 mL: 4 mL) degassed the reaction mixture for 10 min with nitrogen. Then added Pd(PPh3)4 (50 mg, 0.044 mmol), degassed the reaction mixture for additional 10 min with nitrogen, the reaction mixture was heated to 120° C. in microwave for 1 h. The reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (2×30 mL). Combined organic layers was dried over Na2SO4 and concentrated under reduced pressure. Crude product was purified by silica (100-200 mesh) column eluted with 80-90% ethyl acetate in pet-ether to afford 195 mg (Yield: 58.13%) of the title compound as a pale yellow solid. Product was converted to its HCl salt by using HCl in ether (2M) to afford 202 mg as a pale yellow solid.

Workup

  1. customwater (8 mL: 4 mL) degassed the reaction mixture for 10 min with nitrogen
  2. extractionextracted with ethyl acetate (2×30 mL)
  3. dry with materialCombined organic layers was dried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customCrude product was purified by silica (100-200 mesh) column
  6. washeluted with 80-90% ethyl acetate in pet-ether

Sources & evidence

ORD record
ord-a1ab4c14534740c6a7a7c83d769eddb1
Source dataset
uspto-grants-2016_07
Patent number
US09393248B1

Reaction notes

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