Triethylamine → 3-methyl-1-(oxan-4-yl)-1H-pyrazol-5-amine

HRID 1522424ノート

反応式

HRID 1522424 の反応式
N/[C:2](/[CH3:6])=[CH:3]\[C:4]#[N:5].[O:7]1[CH2:12][CH2:11][CH:10]([NH:13][NH2:14])[CH2:9][CH2:8]1.C(N(CC)CC)C>C(O)C>[CH3:6][C:2]1[CH:3]=[C:4]([NH2:5])[N:13]([CH:10]2[CH2:11][CH2:12][O:7][CH2:8][CH2:9]2)[N:14]=1

参加物

5

反応物 3

HCID 8471TriethylamineHCID 5325263(2Z)-3-Amino-2-butenenitrileHCID 10057480(Tetrahydro-2H-pyran-4-yl)hydrazine

生成物 1

HCID 566043973-methyl-1-(oxan-4-yl)-1H-pyrazol-5-amine収率 57%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

反応条件

温度
75 °C

実験手順

(2Z)-3-Amino-2-butenenitrile (0.538 g, 6.55 mmol), tetrahydro-2H-pyran-4-ylhydrazine (1 g, 6.55 mmol) and triethylamine (0.913 mL, 6.55 mmol) were added to ethanol (300 mL), and the reaction mixture was stirred at 75° C. for 16 hours. The solvent was removed in vacuo, and the crude material suspended in EtOAc. The organic phase was washed with water and then brine. The organic layer was then dried over MgSO4, filtered, and concentrated in vacuo. Half of the crude material was purified by reverse HPLC (mobile phase: 0-30% ACN/H2O, 0.1% TFA) to afford 380 mg of the desired product. The other half of the crude material was purified via silica gel chromatography (eluent: 0% to 100% EtOAc:Hex then 0% to 20% MeOH:DCM). An additional 300 mg of the desired product was obtained (overall yield: 57%). LCMS E-S (M+H)=182.0. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.78 (dd, 2 H), 1.94 (qd, J=12.13, 4.55 Hz, 2 H), 2.19 (s, 3 H), 3.30-3.46 (m, 2 H), 3.99 (dd, J=11.49, 4.17 Hz, 2 H), 4.49 (m, J=11.65, 11.65, 4.11, 3.92 Hz, 1 H), 5.53 (s, 1 H).

後処理

  1. customThe solvent was removed in vacuo
  2. washThe organic phase was washed with water
  3. dry with materialThe organic layer was then dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customHalf of the crude material was purified by reverse HPLC (mobile phase: 0-30% ACN/H2O, 0.1% TFA)

出典と根拠

ORDレコード
ord-deb75d8d5caf4682b3d9e069995b22cf
出典データセット
uspto-grants-2015_07
特許番号
US09073924B2

反応ノート

読み込み中…