Cesium carbonate → [3-[6-Amino-5-(1-isopropyltriazol-4-yl)-3-pyridyl]phenyl]-morpholino-methanone

HRID 1053142Notes

Reaction equation

HRID 1053142 reaction equation
C([O-])([O-])=O.[Cs+].[Cs+].Br[C:8]1[CH:9]=[C:10]([C:15]2[N:16]=[N:17][N:18]([CH:20]([CH3:22])[CH3:21])[CH:19]=2)[C:11]([NH2:14])=[N:12][CH:13]=1.[N:23]1([C:29]([C:31]2[CH:32]=[C:33](B(O)O)[CH:34]=[CH:35][CH:36]=2)=[O:30])[CH2:28][CH2:27][O:26][CH2:25][CH2:24]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>[NH2:14][C:11]1[N:12]=[CH:13][C:8]([C:35]2[CH:36]=[C:31]([C:29]([N:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)=[O:30])[CH:32]=[CH:33][CH:34]=2)=[CH:9][C:10]=1[C:15]1[N:16]=[N:17][N:18]([CH:20]([CH3:22])[CH3:21])[CH:19]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 36029163-(Morpholine-4-carbonyl)phenylboronic acidHCID 902731555-bromo-3-(1-isopropyl-1H-[1,2,3]triazol-4-yl)-pyridin-2-ylamine

Product 1

HCID 77106560[3-[6-Amino-5-(1-isopropyltriazol-4-yl)-3-pyridyl]phenyl]-morpholino-methanoneYield 60.8%

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 5-bromo-3-(1-isopropyl-1H-[1,2,3]triazol-4-yl)-pyridin-2-ylamine (250 mg, 0.88 mmol) and (3-(morpholine-4-carbonyl)phenyl)boronic acid (228 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. After completion of reaction, 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 210 mg (Yield: 60.34%) of the title compound as a pale yellow solid. Product was converted to its HCl salt by using HCl in ether (2M) to afford 208 mg as an off-white solid.

Workup

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

Sources & evidence

ORD record
ord-b0523277be4c4d29a2db1067b7ca5747
Source dataset
uspto-grants-2016_07
Patent number
US09393248B1

Reaction notes

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