Methyl triflate → HCID 135932169, compound

HRID 1350439Notes

Reaction equation

HRID 1350439 reaction equation
FC(F)(F)S(OC)(=O)=O.[CH3:10][C:11]1[S:20][C:19]2[NH:18][C:17]3[CH:21]=[CH:22][CH:23]=[CH:24][C:16]=3[NH:15][C:14](=S)[C:13]=2[CH:12]=1.[S:26]1[CH:30]=[CH:29][C:28]([CH2:31][CH2:32][C@H:33]2[CH2:38][NH:37][CH2:36][CH2:35][NH:34]2)=[CH:27]1.S1C=CC=C1CC[C@H]1CNCCN1>ClCCl.CO.ClCCl.N1C=CC=CC=1>[CH3:10][C:11]1[S:20][C:19]2[NH:18][C:17]3[CH:21]=[CH:22][CH:23]=[CH:24][C:16]=3[N:15]=[C:14]([N:37]3[CH2:36][CH2:35][NH:34][C@@H:33]([CH2:32][CH2:31][C:28]4[CH:29]=[CH:30][S:26][CH:27]=4)[CH2:38]3)[C:13]=2[CH:12]=1

Participants

8

Reactant 4

HCID 9526Methyl triflateHCID 210935012-Methyl-5,10-dihydro-4H-thieno[2,3-b][1,5]benzodiazepine-4-thioneHCID 58860719(S)-2-(2-thiophen-3-yl-ethyl)-piperazineHCID 69489506(S)-2-(2-thiophen-2-yl-ethyl)-piperazine

Product 1

HCID 135932169HCID 135932169, compound

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 6344DichloromethaneSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
0 °C

Procedure

Add methyl trifluoromethanesulfonate (241 μL, 2.13 mmol) to a 0° C. slurry of 2-methyl-4,9-dihydro-3-thia-4,9-diaza-benzo[f]azulene-10-thione (437 mg, 1.77 mmol) in dichloromethane (5 mL). Stir 2 h at 0° C. then warm to ambient temperature and stir 16 h. Concentrate the reaction to an orange powder. Add a 6:1 mixture of (S)-2-(2-thiophen-3-yl-ethyl)-piperazine and (S)-2-(2-thiophen-2-yl-ethyl)-piperazine (346 mg, 1.76 mmol) and pyridine (5 mL). Heat to reflux for 7.5 h and stir at ambient temperature for 18 h. Concentrate the reaction, dissolve the residue in methanol-dichloromethane, apply to a SCX column. Wash the column with methanol-dichloromethane to remove impurities then elute the product with 2N ammonia in methanol-methanol (10%). Concentrate and purify by silica gel chromatography using 2N ammonia in methanol-methylene chloride (1%–4%) as the eluent to give 333 mg of a brown foam. Purify by radial silica gel chromatography using a 4 mm plate and 1% isopropylamine in tetrahydrofuran-hexanes (10%–20%) as the eluent to give 218 mg (30%) of the title compound: mass spectrum (ion spray): m/z=409 (M+1), 407 (M −1). HR-MS calculated for C22H25N4S2: 409.1521. Found 409.1540. 1H NMR (DMSO-d6): δ 7.56 (s, 1H), 7.43 (dd, 1H), 7.13 (s, 1H), 6.99 (d, 1H), 6.87–6.74 (m, 3H), 6.67 (d, 1H), 6.31 (s, 1H), 3.88 (br d, 1H), 3.76 (br d, 1H), 2.88 (br d, 1H), 2.80–2.53 (m, 5H), 2.45–2.38 (m, 1H), 2.27 (s, 3H), 1.61 (dd, 2H).

Workup

  1. temperaturethen warm to ambient temperature
  2. stirringstir 16 h
  3. concentrationConcentrate
  4. customthe reaction to an orange powder
  5. additionAdd
  6. temperatureHeat
  7. temperatureto reflux for 7.5 h
  8. stirringstir at ambient temperature for 18 h
  9. concentrationConcentrate
  10. customthe reaction
  11. washWash the column with methanol-dichloromethane
  12. customto remove impurities
  13. washthen elute the product with 2N ammonia in methanol-methanol (10%)
  14. concentrationConcentrate
  15. custompurify by silica gel chromatography

Sources & evidence

ORD record
ord-597b8d98a23549dc9002f7060786d068
Source dataset
uspto-grants-2007_05
Patent number
US07214673B2

Reaction notes

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