Ethylenediamine → HCID 22346473, compound

HRID 897329Notes

Reaction equation

HRID 897329 reaction equation
Br[C:2]1[N:11]=[C:10]([C:12]([NH:14][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)=[O:13])[C:9]([OH:23])=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.[CH2:24]([NH2:27])[CH2:25][NH2:26].C(N(C(C)C)CC)(C)C.[C:37](N1C=CN=C1)(N1C=CN=C1)=[O:38].C(O)(C(F)(F)F)=O>CN1C(=O)N(C)CCC1>[F:22][C:19]1[CH:20]=[CH:21][C:16]([CH2:15][NH:14][C:12]([C:10]2[C:9]([OH:23])=[C:8]3[C:3]([CH:4]=[CH:5][CH:6]=[N:7]3)=[C:2]([N:26]3[CH2:25][CH2:24][NH:27][C:37]3=[O:38])[N:11]=2)=[O:13])=[CH:17][CH:18]=1

Participants

7

Reactant 5

HCID 3301Ethylenediamine2×HCID 6422Trifluoroacetic acidHCID 682631,1'-CarbonyldiimidazoleHCID 81531Diisopropylethylamine2×HCID 223464015-bromo-N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide

Product 1

HCID 22346473HCID 22346473, compound

Reagents, catalysts & solvents 1

HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent

Procedure

A solution of 5-bromo-N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide (0.21 g, 0.55 mmol), ethylene diamine (0.14 mL, 1.67 mmol) and diisopropylethylamine (0.29 mL, 1.67 mmol) in DMPU (2.0 mL) were heated at 140 C for 16 hr. Ethylene diamine (0.14 mL, 1.67 mmol) was added and the reaction heated at 140 C for a further 24 hr. The reaction was cooled to room temperature, and treated with carbonyldiimidazole (0.188 g 1.16 mmol) and diisopropylethylamine (0.29 mL, 1.67 mmol) and then heated at 120 C for 1 hr. The reaction was cooled to room temperature, acidified by the addition of TFA (0.5 mL) and purified by reverse phase HPLC. (Waters PrePak 500 cartridge C18, Gradient elution with Water:Acetonitrile 95:5 to 5:95 with 0.1% TFA at 75 mL/min over 45 mins). Lyophilization of the pure fractions afforded the title compound as an off white solid.

Workup

  1. temperaturethe reaction heated at 140 C for a further 24 hr
  2. temperatureheated at 120 C for 1 hr
  3. temperatureThe reaction was cooled to room temperature
  4. custompurified by reverse phase HPLC
  5. wash(Waters PrePak 500 cartridge C18, Gradient elution with Water:Acetonitrile 95:5 to 5:95 with 0.1% TFA at 75 mL/min over 45 mins)

Sources & evidence

ORD record
ord-01e01da38de84277a0945522da7d9870
Source dataset
uspto-grants-2005_07
Patent number
US06921759B2

Reaction notes

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