Sodium Carbonate → 2-Amino-3-methoxypyridine

HRID 538405

Reaction equation

HRID 538405 reaction equation
[CH3:1][O:2][C:3]1[C:4]([NH2:18])=[N:5][CH:6]=[C:7](B2OC(C)(C)C(C)(C)O2)[CH:8]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.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>[CH3:1][O:2][C:3]1[C:4]([NH2:18])=[N:5][CH:6]=[CH:7][CH:8]=1

Participants

5

Reactant 2

HCID 10340Sodium CarbonateHCID 533980593-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine

Product 1

HCID 99203842-Amino-3-methoxypyridine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture 4,5-dibromo-2-(4-(trifluoromethyl)phenyl)-1-((2-trimethylsilyl)ethoxy)methyl-1H-imidazole (730 mg, 1.5 mmol) and 3-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (400 mg, 1.6 mmol; Example 17, Step 3), and 2.0 M aqueous Na2CO3 solution (3 mL, 6.0 mmol) in DME (10 mL) was purged with Ar for 3 min. Pd(PPh3)4 (65 mg, 0.055 mmol) was added the reaction was heated to 100° C. by for 20 h. The reaction was allowed to cool to rt and phases partitioned. The organic portion was separated and concentrated. The resulting residue crude was purified by flash chromatography (SiO2; 80:20-0:100 hexanes-EtOAc) to furnish 640 mg (1.2 mmol, 80%) of 5-(5-bromo-2-(4-trifluoromethyl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)-3-methoxypyridin-2-amine: LCMS (m/z): 545.0 (MH+), tR=1.02 min.

Workup

  1. temperatureto cool to rt
  2. customphases partitioned
  3. customThe organic portion was separated
  4. concentrationconcentrated
  5. customThe resulting residue crude was purified by flash chromatography (SiO2; 80:20-0:100 hexanes-EtOAc)

Sources & evidence

ORD record
ord-88d5aa1709c743cb9a37839de5b18ced
Source dataset
uspto-grants-2014_10
Patent number
US08865732B2

Linked notes

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