3-Bromo-1-propanol → (S)-3-[2-(2-Methoxy-ethyl)-4-(2-trifluoromethyl-4H-3-thia-1,4,9-triaza-benzo[f]azulene-10-yl)-piperazin-1-yl]-propan-1-ol

HRID 131509Notes

Reaction equation

HRID 131509 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][C@@H:5]1[NH:10][CH2:9][CH2:8][N:7]([C:11]2[C:20]3[N:19]=[C:18]([C:21]([F:24])([F:23])[F:22])[S:17][C:16]=3[NH:15][C:14]3[CH:25]=[CH:26][CH:27]=[CH:28][C:13]=3[N:12]=2)[CH2:6]1.Br[CH2:30][CH2:31][CH2:32][OH:33]>>[CH3:1][O:2][CH2:3][CH2:4][C@H:5]1[CH2:6][N:7]([C:11]2[C:20]3[N:19]=[C:18]([C:21]([F:23])([F:24])[F:22])[S:17][C:16]=3[NH:15][C:14]3[CH:25]=[CH:26][CH:27]=[CH:28][C:13]=3[N:12]=2)[CH2:8][CH2:9][N:10]1[CH2:30][CH2:31][CH2:32][OH:33]

Participants

3

Reactant 2

HCID 123083-Bromo-1-propanolHCID 135457486(S)-10-[3-(2-Methoxy-ethyl)-piperazin-1-yl]-2-trifluoromethyl-4H-3-thia-1,4,9-triaza-benzo[f]azulene

Product 1

HCID 136090359(S)-3-[2-(2-Methoxy-ethyl)-4-(2-trifluoromethyl-4H-3-thia-1,4,9-triaza-benzo[f]azulene-10-yl)-piperazin-1-yl]-propan-1-ol

Procedure

Using the method of Example 351, using (S)-10-[3-(2-methoxy-ethyl)-piperazin-1-yl]-2-trifluoromethyl-4H-3-thia-1,4,9-triaza-benzo[f]azulene and 3-bromo-propan-1-ol, 15 hours at reflux after the addition of alcohol, and two purifications by flash chromatography: the first, eluting with a gradient of a 3% solution of methanol in ethyl acetate (0-100%), and then with a gradient of methanol: ethyl acetate (3%-5% methanol in ethyl acetate); and the second, eluting with a gradient of solutions of 2M ammonia in methanol, in ethyl acetate (4%-5% over 40 minutes), gives the title compound: mass spectrum (APCI, m/e): 470 (M+1); NMR (1H, 300 MHz, DMSO-d6): δ 8.47 (s, 1H), 6.96-6.81 (m, 3H), 6.70 (m, 1H), 4.42 (m, 1H), 3.54-3.37 (m, 6H), 3.37-3.18 (m, 2H), 3.15 (s, 3H), 2.68 (m, 2H), 2.58-2.45 (m, 1H), 2.35 (m, 2H), 1.68 (m, 2H), 1.55 (m, 2H).

Workup

  1. temperatureat reflux
  2. washthe first, eluting with a gradient of a 3% solution of methanol in ethyl acetate (0-100%)
  3. washand the second, eluting with a gradient of solutions of 2M ammonia in methanol, in ethyl acetate (4%-5% over 40 minutes)

Sources & evidence

ORD record
ord-2c236a1b645d475490b397ea20dd178e
Source dataset
uspto-grants-2008_06
Patent number
US07384934B2

Reaction notes

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