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

HRID 1623256노트

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HRID 1623256 반응식
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

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 27832882,3,6-TrifluoropyridineHCID 552854014-(Aminomethyl)oxane-4-carbonitrile2회

생성물 1

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

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

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온도
105 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-03179a1cd5a14bc18006019280c55140
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08778951B2

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