Triethylamine → ((3,6-difluoropyridin-2-yl-amino)methyl)tetrahydro-2H-pyran-4-carbonitrile

HRID 1623256ノート

反応式

HRID 1623256 の反応式
F[C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([F:9])[N:3]=1.NC[C:12]1([C:18]#[N:19])[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1.[CH2:20]([N:22](CC)CC)C>CS(C)=O>[F:8][C:7]1[C:2]([NH:22][CH2:20][CH:14]2[CH2:13][CH:12]([C:18]#[N:19])[CH2:17][CH2:16][O:15]2)=[N:3][C:4]([F:9])=[CH:5][CH:6]=1

参加物

5

反応物 3

HCID 8471TriethylamineHCID 27832882,3,6-TrifluoropyridineHCID 552854014-(Aminomethyl)oxane-4-carbonitrile2 回

生成物 1

HCID 86689268((3,6-difluoropyridin-2-yl-amino)methyl)tetrahydro-2H-pyran-4-carbonitrile収率 48.3%

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

反応条件

温度
105 °C

実験手順

To 2,3,6-Trifluoropyridine (0.6 g, 4.5 mmol) in DMSO (5 ml) at room temperature was added 4-(aminomethyl)tetrahydro-2H-pyran-4-carbonitrile (Intermediate R, 1.01 g, 7.23 mmol) and triethylamine (1.57 ml, 11.24 mmol) sequentially. The light brown mixture was heated at 105° C. in a sealed glass bomb for 18 hours. After cooled to room temperature the reaction mixture was extracted with EtOAc (40 ml), washed with saturated NaHCO3 solution and brine, dried over sodium sulfate and concentrated in vacuo to give a light brown liquid. This crude material was purified by silica gel chromatography using a 12 g column, eluting with 5%-20% ethyl acetate in hexane to afford 550 mg (48.2% yield) of the desired product. LCMS (m/z): 254.1 [M+H]+; retention time=0.743 min. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.69-1.95 (m, 4H) 3.60-3.82 (m, 4H) 4.00 (ddd, J=12.13, 4.30, 1.96 Hz, 2H) 5.02 (br. S., 1H) 6.12 (td, J=5.58, 2.54 Hz, 1H) 7.19-7.33 (m, 1H).

後処理

  1. temperatureAfter cooled to room temperature the reaction mixture
  2. extractionwas extracted with EtOAc (40 ml)
  3. washwashed with saturated NaHCO3 solution and brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customto give a light brown liquid
  7. customThis crude material was purified by silica gel chromatography
  8. washeluting with 5%-20% ethyl acetate in hexane

出典と根拠

ORDレコード
ord-03179a1cd5a14bc18006019280c55140
出典データセット
uspto-grants-2014_07
特許番号
US08778951B2

反応ノート

読み込み中…