2,2,2-Trifluoroethyl trifluoromethanesulfonate → HCID 58204747, compound

HRID 1498437Notes

Reaction equation

HRID 1498437 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3](O)=O.[CH:8]([N:11]1[C:15]([C:16]2[N:25]=[C:24]3[N:18]([CH2:19][CH2:20][O:21][C:22]4[CH:29]=[C:28]([CH:30]5[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]5)[CH:27]=[CH:26][C:23]=43)[CH:17]=2)=[N:14][CH:13]=[N:12]1)([CH3:10])[CH3:9].FC(F)(F)S(OCC(F)(F)F)(=O)=O>C1COCC1>[CH:8]([N:11]1[C:15]([C:16]2[N:25]=[C:24]3[C:23]4[CH:26]=[CH:27][C:28]([CH:30]5[CH2:35][CH2:34][N:33]([CH2:3][C:2]([F:7])([F:6])[F:1])[CH2:32][CH2:31]5)=[CH:29][C:22]=4[O:21][CH2:20][CH2:19][N:18]3[CH:17]=2)=[N:14][CH:13]=[N:12]1)([CH3:10])[CH3:9]

Participants

4

Reactant 2

HCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 670507222-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-8-piperidin-4-yl-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene trifluoroacetic acid salt

Product 1

HCID 58204747HCID 58204747, compoundYield 23%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A suspension of 2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-8-piperidin-4-yl-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene trifluoro acetate (250 mg, 0.51 mmol) in THF (5 mL) was treated with TEA and the mixture flushed with argon. 2,2,2-trifluoroethyl trifluoromethane sulfonate (0.15 mL, 1.02 mmol) was added and the mixture stirred at RT for 72 h. The reaction mixture was partitioned between DCM and water, the organic layer washed with saturated aqueous sodium hydrogen carbonate followed by brine and then dried (MgSO4), filtered and concentrated in vacuo. The resultant residue was dissolved in 1.25 M HCl in methanol then concentrated in vacuo to give a solid which was triturated in IPA then diethyl ether. The resultant solid was subjected to RPHPLC (C18 column, gradient 10 to 98% methanol in water+0.1% HCO2H) to give 361 as a white solid (49 mg, 23%). LCMS: RT=4.59 min, [M+H]+=461. 1H NMR 400 MHz (DMSO-d6) δ: 8.33 (1 H, d, J=8.29 Hz), 7.91-7.91 (2 H, m), 7.08 (1 H, dd, J=8.36, 1.79 Hz), 6.92 (1 H, m), 5.91-5.90 (1 H, m), 4.51 (4 H, q, J=5.90 Hz), 3.21 (2 H, q, J=10.30 Hz), 3.03 (2 H, d, J=11.25 Hz), 2.45 (3 H, m), 1.76 (2 H, m), 1.69-1.67 (2 H, m), 1.49 (6 H, d, J=6.60 Hz)

Workup

  1. additionwas treated with TEA
  2. customthe mixture flushed with argon
  3. customThe reaction mixture was partitioned between DCM and water
  4. washthe organic layer washed with saturated aqueous sodium hydrogen carbonate
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. dissolutionThe resultant residue was dissolved in 1.25 M HCl in methanol
  9. concentrationthen concentrated in vacuo
  10. customto give a solid which
  11. customwas triturated in IPA

Sources & evidence

ORD record
ord-4308b18d62fa494da18ee225b281f4d3
Source dataset
uspto-grants-2015_12
Patent number
US09198918B2

Reaction notes

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