Methanol → (S)-10-[4-(2-Fluoro-ethyl)-3-(2-methoxy-ethyl)-piperazin-1-yl]-2-trifluoromethyl-4H-3-thia-1,4,9-triaza-benzo[f]azulene

HRID 131505Notes

Reaction equation

HRID 131505 reaction equation
B.O1CCCC1.[F:7][CH2:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:17]2[C:26]3[N:25]=[C:24]([C:27]([F:30])([F:29])[F:28])[S:23][C:22]=3[NH:21][C:20]3[CH:31]=[CH:32][CH:33]=[CH:34][C:19]=3[N:18]=2)[CH2:13][C@@H:12]1[CH2:35][CH2:36][O:37][CH3:38])=O.CO.C(N)CN>O1CCCC1.O.ClCCl>[F:7][CH2:8][CH2:9][N:11]1[CH2:16][CH2:15][N:14]([C:17]2[C:26]3[N:25]=[C:24]([C:27]([F:30])([F:29])[F:28])[S:23][C:22]=3[NH:21][C:20]3[CH:31]=[CH:32][CH:33]=[CH:34][C:19]=3[N:18]=2)[CH2:13][C@@H:12]1[CH2:35][CH2:36][O:37][CH3:38]

Participants

8

Reactant 4

HCID 887MethanolHCID 3301EthylenediamineHCID 2723981Borane;tetrahydrofuranHCID 136090351(S)-2-Fluoro-1-[2-(2-methoxy-ethyl)-4-(2-trifluoromethyl-4H-3-thia-1,4,9-triaza-benzo[f]azulen-10-yl)-piperazin-1-yl]-ethanone

Product 1

HCID 136090347(S)-10-[4-(2-Fluoro-ethyl)-3-(2-methoxy-ethyl)-piperazin-1-yl]-2-trifluoromethyl-4H-3-thia-1,4,9-triaza-benzo[f]azulene

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Add a solution of borane-tetrahydrofuran complex (1.0 M in tetrahydrofuran; 3.8 mL, 3.8 mmol) to a 0° C. solution of (S)-2-fluoro-1-[2-(2-methoxy-ethyl)-4-(2-trifluoromethyl-4H-3-thia-1,4,9-triaza-benzo[f]azulen-10-yl)-piperazin-1-yl]-ethanone (0.18 g, 0.38 mmol) in anhydrous tetrahydrofuran (3 mL) and stir at 0° C. for 3 hours. Quench the reaction, in an ice/water bath, slowly with methanol. Concentrate the reaction under reduced pressure and reconstitute in anhydrous dichloroethane (6 mL). Add ethylenediamine (0.23 mL, 3.4 mmol) and reflux for 45 minutes. Cool the reaction to ambient temperature and dilute with deionized water and dichloromethane (20 mL each). Separate the organic layer and extract the aqueous layer with dichloromethane (2×). Wash the combined organics with deionized water and then a saturated solution of sodium chloride, and then dry (sodium sulfate), filter, and concentrate under reduced pressure to an orange oil (0.19 g). Purify the oil by flash chromatography, eluting with a gradient of a solution of ethyl acetate:hexane (1:1, 0-50% in hexane over 45 minutes, then 100% for 13 minutes) to give the title compound: 0.050 g (29%). Mass spectrum (APCI+, m/e): 458 (M+1).

Workup

  1. customQuench
  2. customthe reaction
  3. concentrationConcentrate
  4. customthe reaction under reduced pressure and reconstitute in anhydrous dichloroethane (6 mL)
  5. temperatureCool
  6. customthe reaction to ambient temperature
  7. customSeparate the organic layer
  8. extractionextract the aqueous layer with dichloromethane (2×)
  9. washWash the combined organics with deionized water
  10. dry with materiala saturated solution of sodium chloride, and then dry (sodium sulfate)
  11. filtrationfilter
  12. concentrationconcentrate under reduced pressure to an orange oil (0.19 g)
  13. customPurify the oil by flash chromatography
  14. washeluting with a gradient of a solution of ethyl acetate:hexane (1:1, 0-50% in hexane over 45 minutes

Sources & evidence

ORD record
ord-bb4991a90cd841a788b8dd9cdf23b2e3
Source dataset
uspto-grants-2008_06
Patent number
US07384934B2

Reaction notes

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