Methane → N-Cyclopropyl-4-oxazol-5-yl-N-piperidin-4-yl-benzamide

HRID 68754ノート

反応式

HRID 68754 の反応式
F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[O:23]1[C:27]([C:28]2[CH:36]=[CH:35][C:31]([C:32]([OH:34])=O)=[CH:30][CH:29]=2)=[CH:26][N:25]=[CH:24]1.C(N(C(C)C)C(C)C)C.C(OC([N:53]1[CH2:58][CH2:57][CH:56]([NH:59][CH:60]2[CH2:62][CH2:61]2)[CH2:55][CH2:54]1)=O)(C)(C)C.C>CN(C)C=O>[CH:60]1([N:59]([CH:56]2[CH2:57][CH2:58][NH:53][CH2:54][CH2:55]2)[C:32](=[O:34])[C:31]2[CH:30]=[CH:29][C:28]([C:27]3[O:23][CH:24]=[N:25][CH:26]=3)=[CH:36][CH:35]=2)[CH2:62][CH2:61]1

参加物

7

反応物 5

HCID 297MethaneHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 2769591tert-Butyl 4-(cyclopropylamino)piperidine-1-carboxylateHCID 27764144-(1,3-Oxazol-5-yl)benzoic Acid

生成物 1

HCID 68289931N-Cyclopropyl-4-oxazol-5-yl-N-piperidin-4-yl-benzamide

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

2-(1H-Benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (6.10 g) is added to a solution of 4-oxazol-5-yl-benzoic acid (3.00 g) and ethyldiisopropylamine (5.56 mL) in N,N-dimethylformamide (50 mL) at room temperature. The solution is stirred for 10 min prior to the addition of 4-cyclopropylamino-piperidine-1-carboxylic acid tert-butyl ester (4.57 g). The resulting mixture is kept at room temperature over night. The mixture is treated with activated charcoal and filtered through a pad of basic aluminum oxide. The pad is washed with N,N-dimethylformamide/methanol (9:1) and the combined filtrates are concentrated in vacuo. The residue is dissolved in 1,4-dioxane (35 mL), a 4 M solution of hydrogen chloride in 1,4-dioxane (20 mL) is added and the resulting mixture is stirred at room temperature for 2 h. The solvent is evaporated and the residue is taken up in water. The resulting mixture is washed with dichloromethane, basified with NaOH solution and extracted with dichloromethane. The combined extracts are dried over Na2SO4 and concentrated in vacuo. The residue is triturated with diethyl ether to afford the title compound. LC (method 1): tR=0.70 min; Mass spectrum (ESI+): m/z=312 [M+H]+.

後処理

  1. waitThe resulting mixture is kept at room temperature over night
  2. filtrationfiltered through a pad of basic aluminum oxide
  3. washThe pad is washed with N,N-dimethylformamide/methanol (9:1)
  4. concentrationthe combined filtrates are concentrated in vacuo
  5. dissolutionThe residue is dissolved in 1,4-dioxane (35 mL)
  6. additiona 4 M solution of hydrogen chloride in 1,4-dioxane (20 mL) is added
  7. stirringthe resulting mixture is stirred at room temperature for 2 h
  8. customThe solvent is evaporated
  9. washThe resulting mixture is washed with dichloromethane
  10. extractionextracted with dichloromethane
  11. dry with materialThe combined extracts are dried over Na2SO4
  12. concentrationconcentrated in vacuo
  13. customThe residue is triturated with diethyl ether

出典と根拠

ORDレコード
ord-4b8e784a4c4945f8ab547907d432cb85
出典データセット
uspto-grants-2014_09
特許番号
US08822471B2

反応ノート

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