Benzene → Ethyl 6-cyclopropyl-1-{[4-(methyloxy)phenyl]methyl}-1H-pyrazolo[3,4-b]pyridine-4-carboxylate

HRID 1522429노트

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HRID 1522429 반응식
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][N:10]2[C:14]([NH2:15])=[CH:13][CH:12]=[N:11]2)=[CH:5][CH:4]=1.[CH:16]1([C:19](=O)[CH2:20][C:21](=O)[C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH2:18][CH2:17]1.C1C=CC=CC=1>CC(O)=O>[CH:16]1([C:19]2[CH:20]=[C:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[C:13]3[CH:12]=[N:11][N:10]([CH2:9][C:6]4[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=4)[C:14]=3[N:15]=2)[CH2:17][CH2:18]1

참가 물질

5

반응물 3

HCID 241BenzeneHCID 31612621-((4-methoxyphenyl)methyl)-1H-pyrazol-5-amineHCID 16779961Ethyl 4-cyclopropyl-2,4-dioxobutanoate

생성물 1

HCID 67124423Ethyl 6-cyclopropyl-1-{[4-(methyloxy)phenyl]methyl}-1H-pyrazolo[3,4-b]pyridine-4-carboxylate수율 71%

시약·촉매·용매 1

HCID 176Acetic Acid용매

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온도
63 °C

실험 절차

A mixture of 1-{[4-(methyloxy)phenyl]methyl}-1H-pyrazol-5-amine (3 g, 14.76 mmol), ethyl 4-cyclopropyl-2,4-dioxobutanoate (2.72 g, 14.76 mmol) and benzene (50 mL) were heated at 63° C. for 16 h. The solvent was removed under reduced pressure. The crude residue was purified via silica gel chromatography (eluent: 0 to 25% EtOAc:Hex) to afford 2.56 g of the desired cyclized product and 1.71 g of the uncyclized adduct. The uncyclized adduct was dissolved in 25 mL of AcOH and heated to reflux for 16 hours. The solvent was removed under reduced pressure and the residue purified via silica gel chromatography (eluent: 0 to 25% EtOAc:Hex) to afford an additional 1.15 g of the desired cyclized product (combined yield=71%). LCMS E-S (M+H)=352.3. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.07-1.13 (m, 4 H) 1.38 (t, J=7.07 Hz, 3 H) 2.39 (s, 1 H) 3.67 (s, 3 H) 4.41 (q, J=7.07 Hz, 2 H) 5.51 (s, 2 H) 6.84 (d, J=8.84 Hz, 2 H) 7.21 (d, J=8.59 Hz, 2 H) 7.64 (s, 1 H) 8.23 (s, 1 H).

후처리

  1. customThe solvent was removed under reduced pressure
  2. customThe crude residue was purified via silica gel chromatography (eluent: 0 to 25% EtOAc:Hex)
  3. customto afford 2.56 g of the
  4. temperatureheated
  5. temperatureto reflux for 16 hours
  6. customThe solvent was removed under reduced pressure
  7. customthe residue purified via silica gel chromatography (eluent: 0 to 25% EtOAc:Hex)
  8. customto afford an additional 1.15 g of the desired cyclized product (combined yield=71%)

출처 및 근거

ORD 기록
ord-19a4b9fa60654d7ea53a3488dd7c40b7
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09073924B2

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