Sodium Carbonate → N4-(1-Methylpiperidin-4-yl)-5-phenylpyridine-2,4-diamine

HRID 384683Notes

Reaction equation

HRID 384683 reaction equation
Cl[C:2]1[C:3]([NH:15][CH:16]2[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]2)=[CH:4][C:5]([NH:8]C(=O)C(C)(C)C)=[N:6][CH:7]=1.[C:23]1(B(O)O)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.O>[CH3:22][N:19]1[CH2:18][CH2:17][CH:16]([NH:15][C:3]2[C:2]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[CH:7][N:6]=[C:5]([NH2:8])[CH:4]=2)[CH2:21][CH2:20]1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 59613362N-(5-Chloro-4-(1-methylpiperidin-4-ylamino)pyridin-2-yl)pivalamide

Product 1

HCID 59613481N4-(1-Methylpiperidin-4-yl)-5-phenylpyridine-2,4-diamineYield 238.6%

Reagents, catalysts & solvents 1

HCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
130 °C

Procedure

A solution of the N-(5-chloro-4-(1-methylpiperidin-4-ylamino)pyridin-2-yl)pivalamide (Synthesis 153-C) (0.187 g, 0.57 mmol), phenyl boronic acid (0.140 g, 1.15 mmol), sodium carbonate (0.153 g, 1.43 mmol) and Bedford catalyst (0.003 g, 0.005 mmol) in a mixture of acetonitrile/water (4/1, 3.1 mL) was heated under microwave irradiation for 30 min at 130° C. The crude reaction mixture was purified by ion exchange on SCX-II acidic resin (1 g) eluting with methanol/dichloromethane (1/1), then 2M ammonia-methanol. The basic fractions were combined and the solvent was removed in vacuo. The crude mixture was used without further purification. A solution of the protected amine in 6 M HCl (3 mL) was heated under microwave irradiation at 105° C. for 50 min. The solution was basified with Na2CO3 and extracted with ethyl acetate (3×10 mL). The crude mixture was purified by flash chromatography on silica, eluting with methanol and dichloromethane (1/9), to give the title compound as a colourless solid (0.384 g, 73%).

Workup

  1. customThe crude reaction mixture
  2. customwas purified by ion exchange on SCX-II acidic resin (1 g)
  3. washeluting with methanol/dichloromethane (1/1)
  4. customthe solvent was removed in vacuo
  5. customThe crude mixture was used without further purification
  6. temperatureA solution of the protected amine in 6 M HCl (3 mL) was heated under microwave irradiation at 105° C. for 50 min
  7. extractionextracted with ethyl acetate (3×10 mL)
  8. customThe crude mixture was purified by flash chromatography on silica
  9. washeluting with methanol and dichloromethane (1/9)

Sources & evidence

ORD record
ord-27287188ad464b74ad0cc519ff79a849
Source dataset
uspto-grants-2013_02
Patent number
US08367658B2

Reaction notes

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