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

HRID 476037ノート

反応式

HRID 476037 の反応式
[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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 176Acetic Acid溶媒

反応条件

温度
63 °C

実験手順

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, 4H) 1.38 (t, J=7.07 Hz, 3H) 2.39 (s, 1H) 3.67 (s, 3H) 4.41 (q, J=7.07 Hz, 2H) 5.51 (s, 2H) 6.84 (d, J=8.84 Hz, 2H) 7.21 (d, J=8.59 Hz, 2H) 7.64 (s, 1H) 8.23 (s, 1H).

後処理

  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%)

出典と根拠

ORDレコード
ord-713cd5c3e0594749bf8f50e8b71e09a0
出典データセット
uspto-grants-2014_01
特許番号
US08637509B2

反応ノート

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