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

HRID 1350480Notes

Reaction equation

HRID 1350480 reaction equation
[F:1][C:2]([F:19])([F:18])[C:3]1[S:12][C:11]2[NH:10][C:9]3[CH:13]=[CH:14][CH:15]=[CH:16][C:8]=3[NH:7][C:6](=S)[C:5]=2[N:4]=1.FC(F)(F)S(OC)(=O)=O.[CH3:29][O:30][C:31]1[CH:32]=[C:33]([CH2:37][CH2:38][C@H:39]2[CH2:44][NH:43][CH2:42][CH2:41][NH:40]2)[CH:34]=[CH:35][CH:36]=1>>[CH3:29][O:30][C:31]1[CH:32]=[C:33]([CH2:37][CH2:38][C@@H:39]2[NH:40][CH2:41][CH2:42][N:43]([C:6]3[C:5]4[N:4]=[C:3]([C:2]([F:19])([F:18])[F:1])[S:12][C:11]=4[NH:10][C:9]4[CH:13]=[CH:14][CH:15]=[CH:16][C:8]=4[N:7]=3)[CH2:44]2)[CH:34]=[CH:35][CH:36]=1

Participants

4

Reactant 3

HCID 9526Methyl triflateHCID 17759586(S)-2-(2-(3-Methoxy-phenyl)-ethyl)-piperazineHCID 21093516HCID 21093516, compound

Product 1

HCID 136005622(S)-10-{3-[2-(3-Methoxy-phenyl)-ethyl]-piperazin-1-yl}-2-trifluoromethyl-4H-3-thia-1,4,9-triaza-benzo[f]azuleneYield 67.7%

Procedure

Using a method similar to Example 484, using 2-trifluoromethyl-4,9-dihydro-3-thia-1,4,9-triaza-benzo[f]azulene-10-thione (4.025 g, 13.36 mmol) and methyl trifluoromethanesulfonate (2.27 mL, 20.0 mmol), to form the methylated intermediate. Take 1.38 g of this intermediate (3.0 mmol), combine with (S)2-[2-(3-Methoxy-phenyl)-ethyl]-piperazine (0.65 g, 3.0 mmol), followed by chromatographic purification, eluting with a gradient of a 3.5% solution of 2M ammonia in methanol, in dichloromethane (0–100% in dichloromethane) gives the title compound (0.99 g): mass spectrum (APCI+, m/e): 488 (M+1); 1H NMR (300 MHz, DMSO-d6), δ (ppm): 8.73–8.49 (m, 2H), 7.21–7.15 (m, 1H), 6.99–6.88 (m, 3H), 6.79–6.69 (m, 4H), 4.25–3.98 (br. m, 2H), 3.70 (s, 3H), 3.38–3.17 (m, 3H), 3.14–2.97 (m, 2H), 2.74–2.52 (m, 2H), 1.90–1.80 (m, 2H).

Workup

  1. customto form the methylated intermediate
  2. customfollowed by chromatographic purification
  3. washeluting with a gradient of a 3.5% solution of 2M ammonia in methanol, in dichloromethane (0–100% in dichloromethane)

Sources & evidence

ORD record
ord-0a46ac6a0b704a34b128a9f027d2e9f5
Source dataset
uspto-grants-2007_05
Patent number
US07214673B2

Reaction notes

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