1,8-Diazabicyclo(5.4.0)undec-7-ene → 7-Amino-5-[4-(2-[7-amino-2-(2-furyl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-ylamino]ethyl)phenoxy]-2-(2-furyl)[1,2,4]triazolo[1,5-a][1,3,5]triazine

HRID 5819

Reaction equation

HRID 5819 reaction equation
[NH2:1][C:2]1[N:7]2[N:8]=[C:9]([C:11]3[O:12][CH:13]=[CH:14][CH:15]=3)[N:10]=[C:6]2[N:5]=[C:4]([NH:16][CH2:17][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([OH:25])=[CH:21][CH:20]=2)[N:3]=1.N12CCCN=C1CCCCC2.[NH2:37][C:38]1[N:43]2[N:44]=[C:45]([C:47]3[O:48][CH:49]=[CH:50][CH:51]=3)[N:46]=[C:42]2[N:41]=[C:40](S(C)(=O)=O)[N:39]=1.C(Cl)Cl.CO>C(#N)C>[NH2:37][C:38]1[N:43]2[N:44]=[C:45]([C:47]3[O:48][CH:49]=[CH:50][CH:51]=3)[N:46]=[C:42]2[N:41]=[C:40]([O:25][C:22]2[CH:21]=[CH:20][C:19]([CH2:18][CH2:17][NH:16][C:4]3[N:3]=[C:2]([NH2:1])[N:7]4[N:8]=[C:9]([C:11]5[O:12][CH:13]=[CH:14][CH:15]=5)[N:10]=[C:6]4[N:5]=3)=[CH:24][CH:23]=2)[N:39]=1

Participants

6

Reactant 4

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 1764074-(2-(7-Amino-2-(2-furyl)-(1,2,4)triazolo(2,3-a)-(1,3,5)triazin-5-yl-amino)ethyl)phenolHCID 99708822-(Furan-2-yl)-5-(methylsulfonyl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-amineHCID 21226129Dichloromethane methanol

Product 1

HCID 98718987-Amino-5-[4-(2-[7-amino-2-(2-furyl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-ylamino]ethyl)phenoxy]-2-(2-furyl)[1,2,4]triazolo[1,5-a][1,3,5]triazine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

7-amino-2-(2-furyl)-5-[2-(4-hydroxyphenyl)ethyl]amino[1,2,4]-triazolo[1,5-a][1,3,5]triazine (0.91 g) and 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU, 0.37 ml) were added to a suspension of 7-amino-2-(2-furyl)-5-methylsulphonyl-[1,2,4]triazolo[1,5-a][1,3,5]triazine (0.82 g) in acetonitrile (50 ml) and the resulting mixture was heated under reflux for 17 hours, after which time thin layer chromatography (TLC) analysis on silica plates (eluent: methylene chloride-methanol 19:1 v/v) indicated that no methanesulphonyl starting material remained. The solvent was then evaporated and the residue was purified by column chromatography on silica (75 g) eluting with ethyl acetate-methylene chloride 7:3 v/v. A white solid was obtained, and this was crystallised from isopropanol to afford 7-amino-5-[4-(2-[7-amino-2-(2-furyl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-ylamino]ethyl)phenoxy]-2-(2-furyl)[ 1,2,4]triazolo[1,5-a][1,3,5]triazine, m.p. 285°-289° C.; microanalysis, found: C, 54.1; H, 4.4; N, 30.8%; C24H19N13O3 1.0(C3H7OH) requires: C, 54.2; H, 4.5; N, 30.5%; NMR: 2.92 (t, 2H, phenyl-CH2), 3.55 (q, 2H, CH2-N), 6.67 (m, 2H, 2 furyl-4H), 7.0 (d, 1H, furyl-3H), 7.11 (d, 1H, furyl-3'H), 7.16 and 7.35 (A2B2 pattern, 4H, phenyl-H), 7.5 (br t, 1H, NH rotamers), 7.85 (d, 1H, furyl-5H), 7.89 (d, 1H, furyl-5'H), 8.12 (br s, 2H, NH2) and 8.93 (d, 2H, NH2); m/e (M+H)+ 538.

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureunder reflux for 17 hours
  3. customThe solvent was then evaporated
  4. customthe residue was purified by column chromatography on silica (75 g)
  5. washeluting with ethyl acetate-methylene chloride 7:3 v/v
  6. customA white solid was obtained
  7. customthis was crystallised from isopropanol

Sources & evidence

ORD record
ord-a3390456313144aa978257dac6d1ec7e
Source dataset
uspto-grants-1993_09
Patent number
US05246932

Linked notes

Loading…