Cyanamide → 7,8-Dihydro-6H-indeno[5,6-e][1,2,4]triazin-3-amine 1-Oxide

HRID 1669008Notes

Reaction equation

HRID 1669008 reaction equation
[N+:1]([C:4]1[CH:12]=[C:11]2[C:7]([CH2:8][CH2:9][CH2:10]2)=[CH:6][C:5]=1[NH2:13])([O-])=[O:2].[N:14]#[C:15][NH2:16].[CH]Cl.[OH-].[Na+]>O.CCOCC>[N+:1]1([O-:2])[C:4]2[CH:12]=[C:11]3[C:7](=[CH:6][C:5]=2[N:13]=[C:15]([NH2:16])[N:14]=1)[CH2:8][CH2:9][CH2:10]3

Participants

7

Reactant 4

HCID 9864CyanamideHCID 14798Sodium HydroxideHCID 27636046-nitro-2,3-dihydro-1H-inden-5-amineHCID 6432229CID 6432229

Product 1

HCID 160813107,8-Dihydro-6H-indeno[5,6-e][1,2,4]triazin-3-amine 1-OxideYield 68%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of amine 2 (21.67 g, 121.6 mmol), cyanamide (20.45 g, 486 mmol) and Et2O (10 mL) were mixed together at 80° C., cooled to ca. 50° C., cHCl (20 mL) added dropwise, during which a vigorous reaction occurred, and the mixture was heated at 80° C. for 1 h. The mixture was cooled to 50° C., 7.5 M NaOH solution added until the mixture was strongly basic and the mixture stirred at 100° C. for 8 h. The mixture was cooled, diluted with water (500 mL), and the yellow/green precipitate filtered. The precipitate was washed with water (3×50 mL), washed with ether (3×30 mL) and dried to give crude material (20.93 g, 85%), which can be used without further purification. The material was purified by chromatography, eluting with a gradient (0-5%) of MeOH/DCM, to give 1-oxide 19 (16.72 g, 68%) as a yellow powder: mp (MeOH/DCM) 270-272° C.; 1H NMR [(CD3)2SO] δ 7.92 (s, 1H, H-9), 7.33 (s, 1 H, H-5), 7.11 (br s, 2H, NH2), 2.91-2.99 (m, 4H, H-6, H-8), 2.01-2.09 (m, 2H, H-7); 13C NMR [(CD3)2SO] δ 159.9, 154.0, 148.5, 142.5, 128.7, 119.8, 113.8, 32.4, 31.6, 25.2. Anal. calcd for C10H10N4O: C, 59.4; H, 5.0; N, 27.7. Found: C, 59.4; H, 5.1; N, 27.8%.

Workup

  1. additionwere mixed together at 80° C.
  2. customa vigorous reaction
  3. temperaturethe mixture was heated at 80° C. for 1 h
  4. temperatureThe mixture was cooled to 50° C.
  5. temperatureThe mixture was cooled
  6. filtrationthe yellow/green precipitate filtered
  7. washThe precipitate was washed with water (3×50 mL)
  8. washwashed with ether (3×30 mL)
  9. customdried
  10. customto give crude material (20.93 g, 85%), which
  11. customcan be used without further purification
  12. customThe material was purified by chromatography
  13. washeluting with a gradient (0-5%) of MeOH/DCM

Sources & evidence

ORD record
ord-65d4196efbe04f10b17a23c8abb9e52a
Source dataset
uspto-grants-2011_08
Patent number
US07989451B2

Reaction notes

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