Methyl triflate → HCID 135457497, compound

HRID 131494Notes

Reaction equation

HRID 131494 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[S:15][C:14]2[NH:13][C:12]3[CH:16]=[CH:17][CH:18]=[CH:19][C:11]=3[NH:10][C:9](=S)[C:8]=2[N:7]=1)=[O:5])[CH3:2].FC(F)(F)S(OC)(=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>C(Cl)Cl.N1C=CC=CC=1>[CH2:1]([O:3][C:4]([C:6]1[S:15][C:14]2[NH:13][C:12]3[CH:16]=[CH:17][CH:18]=[CH:19][C:11]=3[N:10]=[C:9]([N:38]3[CH2:37][CH2:36][NH:35][C@@H:34]([CH2:33][CH2:32][O:31][CH3:30])[CH2:39]3)[C:8]=2[N:7]=1)=[O:5])[CH3:2]

Participants

6

Reactant 3

HCID 9526Methyl triflateHCID 55287560(S)-2-(2-Methoxyethyl)piperazineHCID 58626016HCID 58626016, compound

Product 1

HCID 135457497HCID 135457497, compound

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Combine 10-thioxo-9,10-dihydro-4H-3-thia-1,4,9-triaza-benzo[f]azulene-2-carboxylic acid ethyl ester (3.59 g, 11.76 mmol) in 25 mL CH2Cl2 and add methyl trifluoromethanesulfonate (2.41 g, 14.7 mmol) dropwise at 0° C., stir at 0° C. for half hour, and warm to RT. After 2 h, concentrate the reaction mixture under reduced pressure, mix with (S)-2-(2-methoxy-ethyl)-piperazine (0.1.47 g, 10.2 mmol) in 20 mL pyridine and heat to 100° C. After 4 hours, cool the reaction to RT, and concentrate to a residue. Purification by flash chromatography (twice) on silica gel using a gradient (100% CH2Cl2 to 100% mixed solvent of (CH2Cl2: 2N NH3/MeOH=20:1)) over 55 min. gives the title compound: mass spectrum (electrospray) (m/e): C20H25N5O3S, Calc. Mass (M+1): 416.1756, Found: 416.1748. 1H NMR (400 MHz, CDCl3): δ 7.05-6.98 (m, 2H), 6.91-6.85 (m, 1H), 6.65-6.62 (m, 1H), 5.51 (br, 1H), 4.40 (q, 2H, J=7.5 Hz). 4.10 (br, 2H), 3.51 (t, 2H, J=6.0 Hz), 3.32 (s, 3H), 3.30-3.00 (m, 4H), 2.79-2.72 (m, 1H), 1.79-1.66 (m, 2H), 1.38 (t, 3H, J=7.5 Hz).

Workup

  1. temperaturewarm to RT
  2. waitAfter 2 h
  3. concentrationconcentrate the reaction mixture under reduced pressure
  4. temperatureheat to 100° C
  5. waitAfter 4 hours
  6. temperaturecool
  7. customthe reaction to RT
  8. concentrationconcentrate to a residue
  9. customPurification by flash chromatography (twice) on silica gel using
  10. additiona gradient (100% CH2Cl2 to 100% mixed solvent of (CH2Cl2: 2N NH3/MeOH=20:1)) over 55 min.

Sources & evidence

ORD record
ord-efc72bfa4a60429a9e28a79f447c34a7
Source dataset
uspto-grants-2008_06
Patent number
US07384934B2

Reaction notes

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