Pyridine → (S)-10-[3-(2-methoxyethyl)-piperazin-1-yl]-2-cyclopentyl-4H-3-thia-1,4,9-triazabenzo[f]azulene

HRID 131492Notes

Reaction equation

HRID 131492 reaction equation
[CH:1]1([C:6]2[S:15][C:14]3[NH:13][C:12]4[CH:16]=[CH:17][CH:18]=[CH:19][C:11]=4[NH:10][C:9](=S)[C:8]=3[N:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.O(C)S(C(F)(F)F)(=O)=O.[CH3:30][O:31][CH2:32][CH2:33][C@H:34]1[CH2:39][NH:38][CH2:37][CH2:36][NH:35]1.N1C=CC=CC=1>ClCCl>[CH3:30][O:31][CH2:32][CH2:33][C@@H:34]1[NH:35][CH2:36][CH2:37][N:38]([C:9]2[C:8]3[N:7]=[C:6]([CH:1]4[CH2:5][CH2:4][CH2:3][CH2:2]4)[S:15][C:14]=3[NH:13][C:12]3[CH:16]=[CH:17][CH:18]=[CH:19][C:11]=3[N:10]=2)[CH2:39]1

Participants

6

Reactant 4

HCID 1049PyridineHCID 9526Methyl triflateHCID 210934692-Cyclopentyl-4,9-dihydro-3-thia-1,4,9-triaza-benzo{f}azulene-10-thioneHCID 55287560(S)-2-(2-Methoxyethyl)piperazine

Product 1

HCID 135517425(S)-10-[3-(2-methoxyethyl)-piperazin-1-yl]-2-cyclopentyl-4H-3-thia-1,4,9-triazabenzo[f]azuleneYield 52.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Combine 2-cyclopentyl-4,9-dihydro-3-thia-1,4,9-triazabenzo[f]azulene-10-thione (0.529 g, 1.75 mmol) and methyl triflate (0.24 mL, 2.11 mmol) in dichloromethane (3 mL) at 0° C. Stir the mixture at 0° C. for 15 minutes and warm to room temperature overnight. Evaporate the mixture, combine the residue with (S)-2-(2-methoxyethyl)piperazine (0.253 g, 1.75 mmol) and pyridine (3 mL) and heat at reflux overnight. Evaporate the mixture, then dilute with methanol and apply to a 10 g SCX column. Wash with methanol, then elute with a step gradient starting with dichloromethane going to 10% 2N ammonia-methanol in dichloromethane followed by 100% 2N ammonia-methanol to obtain the desired coupled product. Purify by flash chromatography, eluting with a step gradient starting with dichloromethane going to 6% 2N ammonia-methanol in dichloromethane, to give (S)-10-[3-(2-methoxy-ethyl)-piperazin-1-yl]-2-cyclopentyl 4H-3-thia-1,4,9-triazabenzo[f]azulene (0.378 g, 0.918 mmol, 52%) as a yellow amorphous solid: mass spectrum (APCI): m/z=412.2 (M+1).

Workup

  1. customat 0° C
  2. temperaturewarm to room temperature overnight
  3. customEvaporate the mixture
  4. temperatureheat
  5. temperatureat reflux overnight
  6. customEvaporate the mixture
  7. additiondilute with methanol and apply to a 10 g SCX column
  8. washWash with methanol
  9. washelute with a step gradient
  10. customto obtain the
  11. customPurify by flash chromatography
  12. washeluting with a step gradient

Sources & evidence

ORD record
ord-a3129d08ce574a6282fd5cb02f840107
Source dataset
uspto-grants-2008_06
Patent number
US07384934B2

Reaction notes

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