4-Methoxybenzylamine → 4-(3-Bromo-phenylamino)-6-(4-methoxy-benzylamino)-[1,7]naphthyridine-3-carbonitrile

HRID 276856Notes

Reaction equation

HRID 276856 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][N:15]=[C:16](F)[CH:17]=3)[N:12]=[CH:11][C:10]=2[C:20]#[N:21])[CH:5]=[CH:6][CH:7]=1.[CH3:22][O:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28][NH2:29])=[CH:26][CH:25]=1.CO.C(Cl)(Cl)Cl>C(O)C>[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][N:15]=[C:16]([NH:29][CH2:28][C:27]4[CH:30]=[CH:31][C:24]([O:23][CH3:22])=[CH:25][CH:26]=4)[CH:17]=3)[N:12]=[CH:11][C:10]=2[C:20]#[N:21])[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 754524-MethoxybenzylamineHCID 185489794-(3-Bromo-phenylamino)-6-fluoro-[1,7]naphthyridine-3-carbonitrileHCID 21584188Chloroform methanol

Product 1

HCID 129691054-(3-Bromo-phenylamino)-6-(4-methoxy-benzylamino)-[1,7]naphthyridine-3-carbonitrileYield 45%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To 1 g of 4-(3-bromo-phenylamino)-6-fluoro-[1.7]naphthyridine-3-carbonitrile in 25 mL of absolute ethanol was added 2 ml of 4-methoxy-benzylamine. The reaction was refluxed for eight days, stripped of solvents, and passed through a plug of silica gel with 5% methanol/chloroform. Fractions containing product were pooled and further purified by flash chromatography on silica gel with a gradient of 1-2% methanol/chloroform to give 595 mg (45%) of 4-(3-bromo-phenylamino)-6-(4-methoxy-benzylamino)-[1.7]naphthyridine-3-carbonitrile, which was sufficiently pure for further transformations. The product was recrystallized by dissolving in a minimum amount of warm chloroform, diluting with ether, and then adding hexanes to give 195 mg: melting point 82-86° C. (decomposed); mass spectrum (m/e): M+H 460.2, 462.2.

Workup

  1. temperatureThe reaction was refluxed for eight days
  2. additionFractions containing product
  3. customfurther purified by flash chromatography on silica gel with a gradient of 1-2% methanol/chloroform

Sources & evidence

ORD record
ord-7c7ed2f1ce5f4d07a71854f73667b027
Source dataset
uspto-grants-2002_03
Patent number
US06355636B1

Reaction notes

Loading…