Trifluoroacetic acid → 3-(5-(4-((Methylamino)methyl)phenyl)-1,3,4-oxadiazol-2-yl)-5-(4-methylcyclohex-1-enyl)pyrazin-2-amine

HRID 1959467Notes

Reaction equation

HRID 1959467 reaction equation
C(OC([N:8](C(OC(C)(C)C)=O)[C:9]1[C:10]([C:16]2[O:20][C:19]([C:21]3[CH:26]=[CH:25][C:24]([CH2:27][N:28](C)[C:29](=O)OC(C)(C)C)=[CH:23][CH:22]=3)=[N:18][N:17]=2)=[N:11][C:12](Br)=[CH:13][N:14]=1)=O)(C)(C)C.C(P(C(C)(C)C)[C:49]1[CH:57]=[CH:56][C:52](N(C)C)=[CH:51][CH:50]=1)(C)(C)C.[C:62]([O-])([O-])=O.[K+].[K+].C(O)(C(F)(F)F)=O>C1(C)C=CC=CC=1.O.C(Cl)Cl.Cl[Pd]Cl>[CH3:29][NH:28][CH2:27][C:24]1[CH:23]=[CH:22][C:21]([C:19]2[O:20][C:16]([C:10]3[C:9]([NH2:8])=[N:14][CH:13]=[C:12]([C:49]4[CH2:50][CH2:51][CH:52]([CH3:62])[CH2:56][CH:57]=4)[N:11]=3)=[N:17][N:18]=2)=[CH:26][CH:25]=1

Participants

9

Reactant 4

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 11714598(4-(N,N-Dimethylamino)phenyl)di-tert-butyl phosphineHCID 59472131HCID 59472131, compound

Product 1

HCID 667450123-(5-(4-((Methylamino)methyl)phenyl)-1,3,4-oxadiazol-2-yl)-5-(4-methylcyclohex-1-enyl)pyrazin-2-amine

Reagents, catalysts & solvents 4

HCID 24290Palladium ChlorideCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent2×

Procedure

A suspension of tert-butyl N [[4-[5-[3-[bis(tert-butoxycarbonyl)amino]-6-bromo-pyrazin-2-yl]-1,3,4-oxadiazol-2-yl]phenyl]methyl]-N-methyl-carbamate (70 mg, 0.11 mmol), 4-ditert-butylphosphanyl-N,N-dimethyl-aniline; dichloropalladium (0.75 mg, 0.001 mmol) and K2CO3 (29 mg, 0.2 mmol) in toluene (630 μL) and water (70 μL) was heated to 80° C. for 18 h. The reaction mixture was cooled to room temperature and diluted with DCM (30 ml) and water (30 ml). The layers were separated and the organic layer was washed with 1M NaOH solution, dried over (Na2SO4), filtered and concentrated to dryness. The crude material obtained was stirred in 1:1 DCM:TFA mixture (3 mL) for 1 h. The solvents were evaporated under reduced pressure and the crude material was purified by reverse phase chromatography using 1 to 99% MeOH in water (0.05% HCl) to obtain 3-(5-(4-((methylamino)methyl)phenyl)-1,3,4-oxadiazol-2-yl)-5-(4-methylcyclohex-1-enyl)pyrazin-2-amine. 1H NMR (400 MHz, MeOD) δ 8.33-8.21 (m, 3H), 7.79-7.68 (m, 2H), 6.65 (s, 1H), 4.32 (d, J=5.3 Hz, 2H), 3.78-3.61 (m, 2H), 3.34 (d, J=5.4 Hz, 1H), 2.78 (d, J=5.3 Hz, 3H), 2.71 (d, J=14.9 Hz, 1H), 2.42 (ddd, J=22.1, 18.2, 5.7 Hz, 2H), 2.00-1.83 (m, 2H), 1.82-1.69 (m, 1H), 1.40 (dt, J=16.6, 4.6 Hz, 1H), 1.05 (t, J=5.9 Hz, 3H). LC/MS m/z 377.0[M+H]+.

Workup

  1. customThe layers were separated
  2. washthe organic layer was washed with 1M NaOH solution
  3. dry with materialdried over (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. customThe crude material obtained
  7. customThe solvents were evaporated under reduced pressure
  8. customthe crude material was purified by reverse phase chromatography

Sources & evidence

ORD record
ord-da14b49bc3104828b1b69c697cd3d7a5
Source dataset
uspto-grants-2013_04
Patent number
US08410112B2

Reaction notes

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