Sodium Carbonate → 5-(3,6-dihydro-2H-pyran-4-yl)pyridin-3-amine

HRID 1431553Notes

Reaction equation

HRID 1431553 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6](Br)[CH:7]=1.[O:9]1[CH2:14][CH:13]=[C:12](B2OC(C)(C)C(C)(C)O2)[CH2:11][CH2:10]1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.CCO.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>[O:9]1[CH2:10][CH:11]=[C:12]([C:6]2[CH:7]=[C:2]([NH2:1])[CH:3]=[N:4][CH:5]=2)[CH2:13][CH2:14]1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 8176813-Amino-5-bromopyridineHCID 112180533,6-Dihydro-2H-pyran-4-boronic acid pinacol ester

Product 1

HCID 596311705-(3,6-dihydro-2H-pyran-4-yl)pyridin-3-amine

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

A stirred mixture of 3-amino-5-bromopyridine (0.25 g, 1.4 mmol), 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.33 g, 1.6 mmol), tetrakis(triphenylphosphine)palladium (83.3 mg, 0.072 mmol), and 2.0M sodium carbonate (3.6 mL, 7.2 mmol) in toluene (3.0 mL) and EtOH (1.0 mL) was heated to 70° C. After 19 h, the reaction was cooled to rt then diluted with water. After extraction with EtOAc, the organic extraction was dried over anhydrous sodium sulfate. After filtration and concentration, the residue was purified on basic alumina (0-35% EtOAc in hexanes) to afford a white solid as 5-(3,6-dihydro-2H-pyran-4-yl)pyridin-3-amine. 1H NMR (500 MHz, CDCl3) δ ppm 8.05 (1H, d, J=2.0 Hz), 7.96 (1H, d, J=2.7 Hz), 6.95 (1H, m), 6.10 (1H, tt, J=2.9, 1.5 Hz), 4.28 (2H, q, J=2.9 Hz), 3.90 (2H, t, J=5.5 Hz), 3.81 (1H, br. s.), 2.48 (2H, m). Mass Spectrum (pos.) m/e: 177.1 (M+1).

Workup

  1. temperaturethe reaction was cooled to rt
  2. extractionAfter extraction with EtOAc
  3. extractionthe organic extraction
  4. dry with materialwas dried over anhydrous sodium sulfate
  5. filtrationAfter filtration and concentration
  6. customthe residue was purified on basic alumina (0-35% EtOAc in hexanes)

Sources & evidence

ORD record
ord-091bb4e0d8344162b6c630d427fcb1a5
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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