Cesium carbonate → 1-Methyl-4-(3-((5-methyl-2-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)thiazol-4-yl)methyl)phenyl)piperazin-1-ium trifluoroacetate

HRID 517555Notes

Reaction equation

HRID 517555 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:28]=[CH:29][CH:30]=1)[CH2:5][C:6]1[N:7]=[C:8]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=3)[N:13]=2)[S:9][C:10]=1[CH3:11].[C:31]([O-])([O-:33])=[O:32].[Cs+].[Cs+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[CH3:71][N:72]1[CH2:77][CH2:76][NH:75][CH2:74][CH2:73]1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[F:27][C:24]([F:25])([F:26])[C:31]([O-:33])=[O:32].[CH3:71][NH+:72]1[CH2:77][CH2:76][N:75]([C:2]2[CH:30]=[CH:29][CH:28]=[C:4]([CH2:5][C:6]3[N:7]=[C:8]([C:12]4[O:16][N:15]=[C:14]([C:17]5[CH:22]=[CH:21][C:20]([O:23][C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=5)[N:13]=4)[S:9][C:10]=3[CH3:11])[CH:3]=2)[CH2:74][CH2:73]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 531671-MethylpiperazineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 867114955-(4-(3-Bromobenzyl)-5-methylthiazol-2-yl)-3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazole

Product 1

HCID 867114961-Methyl-4-(3-((5-methyl-2-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)thiazol-4-yl)methyl)phenyl)piperazin-1-ium trifluoroacetate

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

Synthesized according to a procedure similar to the following: 5-(4-(3-bromobenzyl)-5-methylthiazol-2-yl)-3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazole was reacted with Cs2CO3 (2 molar equivalents), XPhos (0.4 molar equivalents), Pd2(dba)3 (0.2 molar equivalents), and N-methylpiperazine were placed in a microwave reaction vessel and dioxane (1 mL), which had been degassed by bubbling N2 through it for 10 min, was added. The reaction was heated by microwave irradiation at 120° C. for 1 h and purified by prep-HPLC (MeCN/H2O 40%-80% MeCN, containing 0.1% TFA) (4.5 mg, 11%). MS (ES+) C25H24F3N5O2S requires: 515, found: 516 [M+H]+; 1H-NMR (600 MHz, CD3OD) δ ppm 8.24 (d, J=7.2 Hz, 2H), 7.48 (d, J=7.2 Hz, 2H), 7.22 (t, J=6.0 Hz, 1H), 6.99 (s, 1H), 6.82-6.90 (m, 2H), 4.18 (s, 2H), 3.81 (d, J=13.2 Hz, 2H), 3.57 (d, J=13.2 Hz, 2H), 3.24 (t, J=12.0 Hz, 2H), 3.02 (t, J=12.0 Hz, 2H), 2.95 (s, 3H), 2.57 (s, 3H).

Workup

  1. customSynthesized
  2. customhad been degassed
  3. customby bubbling N2 through it for 10 min
  4. additionwas added
  5. custompurified by prep-HPLC (MeCN/H2O 40%-80% MeCN, containing 0.1% TFA) (4.5 mg, 11%)

Sources & evidence

ORD record
ord-1b75881def62444bb9c7b198d769daac
Source dataset
uspto-grants-2015_08
Patent number
US09115120B2

Reaction notes

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