Methyl triflate → (S)-10-{3-[2-(4-Fluoro-phenyl)-ethyl]-piperazin-1-yl}-2-isopropyl-4H-3-thia-1,4,9-triaza-benzo[f]azulene

HRID 1350462Notes

Reaction equation

HRID 1350462 reaction equation
[CH:1]([C:4]1[S:13][C:12]2[NH:11][C:10]3[CH:14]=[CH:15][CH:16]=[CH:17][C:9]=3[NH:8][C:7](=S)[C:6]=2[N:5]=1)([CH3:3])[CH3:2].FC(F)(F)S([O:24][CH3:25])(=O)=O.[F:28][C:29]1[CH:34]=[CH:33][C:32]([CH2:35][CH2:36][C@H:37]2[CH2:42][NH:41][CH2:40][CH2:39][NH:38]2)=[CH:31][CH:30]=1>ClCCl.N1C=CC=CC=1>[NH3:5].[CH3:25][OH:24].[F:28][C:29]1[CH:34]=[CH:33][C:32]([CH2:35][CH2:36][C@@H:37]2[NH:38][CH2:39][CH2:40][N:41]([C:7]3[C:6]4[N:5]=[C:4]([CH:1]([CH3:3])[CH3:2])[S:13][C:12]=4[NH:11][C:10]4[CH:14]=[CH:15][CH:16]=[CH:17][C:9]=4[N:8]=3)[CH2:42]2)=[CH:31][CH:30]=1

Participants

7

Reactant 3

HCID 9526Methyl triflateHCID 210934792-Isopropyl-4,9-dihydro-3-thia-1,4,9-triazabenzo[f]azulene-10-thioneHCID 69487151(S)-2-(2-(4-Fluoro-phenyl)-ethyl)-piperazine

Product 2

HCID 21705897Ammonia methanolHCID 136005614(S)-10-{3-[2-(4-Fluoro-phenyl)-ethyl]-piperazin-1-yl}-2-isopropyl-4H-3-thia-1,4,9-triaza-benzo[f]azuleneYield 78.7%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

Stir 2-isopropyl-4,9-dihydro-3-thia-1,4,9-triaza-benzo[f]azulene-10-thione (0.551 g, 2.0 mmol) in dichloromethane (10.0 mL) and chilled in an ice bath while adding methyl trifluoromethane sulfonate (0.27 mL, 2.4 mmol). Allow this solution to stir at ambient temperature for 16 hours. Evaporate the solvent to a gray solid. Dissolve this solid and (S)-2-[2-(4-fluoro-phenyl)-ethyl]-piperazine (0.417 g, 2.0 mmol) in pyridine (8.0 mL) and heat at 115° C. for 23 hours. After evaporation of the pyridine, silica gel chromatography, eluting with methylene chloride: 2N NH3/methanol (100:5), gives 0.354 g of the title compound as a yellow solid: mass spectrum (ion spray): m/z=450 (M+1); Analysis for C25H28FN5S(0.2 H2O): calcd: C, 66.26; H, 6.32; N, 15.45; found: C, 66.01; H, 6.15; N, 15.25.

Workup

  1. temperaturechilled in an ice bath
  2. customEvaporate the solvent to a gray solid
  3. temperatureheat at 115° C. for 23 hours
  4. customAfter evaporation of the pyridine, silica gel chromatography
  5. washeluting with methylene chloride

Sources & evidence

ORD record
ord-4ae1470cffe742eea7750ceda4dc7fd8
Source dataset
uspto-grants-2007_05
Patent number
US07214673B2

Reaction notes

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