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

HRID 1350479Notes

Reaction equation

HRID 1350479 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.[F:29][C:30]1[CH:35]=[CH:34][C:33]([CH2:36][CH2:37][C@H:38]2[CH2:43][NH:42][CH2:41][CH2:40][NH:39]2)=[CH:32][CH:31]=1>>[F:29][C:30]1[CH:35]=[CH:34][C:33]([CH2:36][CH2:37][C@@H:38]2[NH:39][CH2:40][CH2:41][N:42]([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)[CH2:43]2)=[CH:32][CH:31]=1

Participants

4

Reactant 3

HCID 9526Methyl triflateHCID 21093516HCID 21093516, compoundHCID 69487151(S)-2-(2-(4-Fluoro-phenyl)-ethyl)-piperazine

Product 1

HCID 136005537(S)-10-{3-[2-(4-Fluoro-phenyl)-ethyl]-piperazin-1-yl}-2-trifluoromethyl-4H-3-thia-1,4,9-triaza-benzo[f]azuleneYield 77.8%

Procedure

Using a method similar to in 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-(4-fluoro-phenyl)-ethyl]-piperazine (0.62, 3.0 mmol), followed by chromatographic purification, eluting with a gradient of a 3.5% solution of 2M ammonia in ethanol, in dichloromethane (0–100% in dichloromethane) gives the title compound (1.11 g): mass spectrum (APCI+, m/e): 476 (M+1); 1H NMR (300 MHz, DMSO-d6), δ (ppm): 8.67–8.36 (m, 2H), 7.27–7.16 (m, 2H), 7.13–7.03 (m, 2H), 7.01–6.86 (m, 3H), 6.75–6.68 (m, 1H), 4.24–3.96 (br. m, 2H), 3.39–2.91 (m, 5H), 2.75–2.51 (m, 2H), 1.88–1.73 (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 ethanol, in dichloromethane (0–100% in dichloromethane)

Sources & evidence

ORD record
ord-44fe4cc7762c4cfb9f73084a8759374d
Source dataset
uspto-grants-2007_05
Patent number
US07214673B2

Reaction notes

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