2,2,2-Trifluoroethyl trifluoromethanesulfonate → 1-N-[7-thia-9,11-diazatricyclo[6.4.0.0^[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]-4-N-(2,2,2-trifluoroethyl)cyclohexane-1,4-diamine

HRID 525111Notes

Reaction equation

HRID 525111 reaction equation
[C:1]12[C:12]([NH:13][CH:14]3[CH2:19][CH2:18][CH:17]([NH2:20])[CH2:16][CH2:15]3)=[N:11][CH:10]=[N:9][C:8]=1[S:7][C:6]1[CH2:5][CH2:4][CH2:3][C:2]2=1.C(S(O[CH2:29][C:30]([F:33])([F:32])[F:31])(=O)=O)(F)(F)F.C1CCN2C(=NCCC2)CC1>CN(C=O)C>[C:1]12[C:12]([NH:13][CH:14]3[CH2:19][CH2:18][CH:17]([NH:20][CH2:29][C:30]([F:33])([F:32])[F:31])[CH2:16][CH2:15]3)=[N:11][CH:10]=[N:9][C:8]=1[S:7][C:6]1[CH2:5][CH2:4][CH2:3][C:2]2=1

Participants

5

Reactant 3

HCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 575201561-N-[7-thia-9,11-diazatricyclo[6.4.0.0^[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]cyclohexane-1,4-diamine

Product 1

HCID 575198041-N-[7-thia-9,11-diazatricyclo[6.4.0.0^[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]-4-N-(2,2,2-trifluoroethyl)cyclohexane-1,4-diamineYield 81%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a 50 mL round-bottom flask containing a solution of 1-N-[7-thia-9,11-diazatricyclo[6.4.0.0^[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]cyclohexane-1,4-diamine (288 mg, 1.00 mmol, 1.00 equiv) in DMF (10 mL) was added F3CSO3CH2CF3 (700 mg, 3.02 mmol, 3.00 equiv) and DBU (457 mg, 3.01 mmol, 3.00 equiv) in ice-water bath under nitrogen. The resulting solution was stirred overnight at 60° C. After completion of the reaction, the reaction solution was cooled down to room temperature and then quenched with water, diluted with DCM (30 mL), washed with brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with DCM/methanol (30:1 to 20:1) to provide the desired 1-N-[7-thia-9,11-diazatricyclo[6.4.0.0^[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]-4-N-(2,2,2-trifluoroethyl)cyclohexane-1,4-diamine (300 mg, 81%) as a white solid. MS (electrospray) m/z 371 (M+H)+; 1H NMR (400 MHz, CD3OD): 8.22 (s, 1H), 4.06-4.14 (m, 1H), 3.24-3.32 (q, 2H), 3.01 (t, 2H), 3.07 (t, 2H), 2.51-2.78 (m, 3H), 2.04-2.15 (m, 4H), 1.43-1.55 (m, 2H), 1.28-1.35 (m, 2H).

Workup

  1. customAfter completion of the reaction
  2. temperaturethe reaction solution was cooled down to room temperature
  3. customquenched with water
  4. additiondiluted with DCM (30 mL)
  5. washwashed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-a3c211fb473c4be2816639c6fe2983bb
Source dataset
uspto-grants-2016_05
Patent number
US09340554B2

Reaction notes

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