Sodium Carbonate → N-(4-amino-5-cyano-6-phenylpyridin-2-yl)acetamide

HRID 1364525Notes

Reaction equation

HRID 1364525 reaction equation
[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6](Br)[N:5]=[C:4]([NH:11][C:12](=[O:14])[CH3:13])[CH:3]=1.C([O-])([O-])=O.[Na+].[Na+].[C:21]1(OB(O)O)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>CN(C=O)C.C1COCC1.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>[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[N:5]=[C:4]([NH:11][C:12](=[O:14])[CH3:13])[CH:3]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 78412Phenyl dihydrogen orthoborateHCID 11557905N-(4-Amino-6-bromo-5-cyano-pyridin-2-yl)-acetamide

Product 1

HCID 11658882N-(4-amino-5-cyano-6-phenylpyridin-2-yl)acetamideYield 72.7%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 86606902water THF DMFSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of bromide from Example 65A (45 mg, 0.18 mmol), Na2CO3 (38 mg, 0.35 mmol), and Pd(PPh3)4 (10 mg, 0.009 mmol) was stirred in DMF/THF/H2O (1:1:0.5) under nitrogen in a microwave reactor vial. Phenyl boric acid (26 mg, 0.21 mmol) was added. The resulting mixture was capped and heated at 130° C. for 20 min in a microwave reactor. The crude mixture was partitioned between EtOAc and water. The organic layer washed with water and brine, dried over Na2SO4, and evaporated under reduced pressure. The crude residue was purified by a Gilson reverse phase HPLC to provide the titled compound (33 mg, 72% yield). 1H NMR (300 MHz, d6-DMSO) δ 10.44 (s, 1H), 7.74-7.68 (m, 2H), 7.55 (s, 1H), 7.52-7.46 (m, 3H), 6.98 (s, 2H), 2.08 (s, 3H). MS (ESI) m/e 253 (M+H)+; m/e 251 (M−H)−.

Workup

  1. customThe resulting mixture was capped
  2. customThe crude mixture was partitioned between EtOAc and water
  3. washThe organic layer washed with water and brine
  4. dry with materialdried over Na2SO4
  5. customevaporated under reduced pressure
  6. customThe crude residue was purified by a Gilson reverse phase HPLC

Sources & evidence

ORD record
ord-5fa09abe9e974bc0b543db820b30e33e
Source dataset
uspto-grants-2011_02
Patent number
US07888374B2

Reaction notes

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