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

HRID 1522424노트

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HRID 1522424 반응식
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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 702Ethanol용매

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온도
75 °C

실험 절차

(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).

후처리

  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)

출처 및 근거

ORD 기록
ord-deb75d8d5caf4682b3d9e069995b22cf
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09073924B2

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