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

HRID 1959467ノート

反応式

HRID 1959467 の反応式
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

参加物

9

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 4

HCID 24290Palladium Chloride触媒HCID 962Water溶媒2 回HCID 1140Toluene溶媒HCID 6344Dichloromethane溶媒2 回

実験手順

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]+.

後処理

  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

出典と根拠

ORDレコード
ord-da14b49bc3104828b1b69c697cd3d7a5
出典データセット
uspto-grants-2013_04
特許番号
US08410112B2

反応ノート

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