Triethylamine → Ethyl 4-chloro-1,6-diethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate

HRID 564429ノート

反応式

HRID 564429 の反応式
[CH2:1]([N:3]1[C:7]([NH2:8])=[CH:6][CH:5]=[N:4]1)[CH3:2].Cl[C:10](=[C:13]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:14](OCC)=O)[CH2:11][CH3:12].C(N(CC)CC)C.P(Cl)(Cl)([Cl:33])=O>C1(C)C=CC=CC=1>[Cl:33][C:14]1[C:13]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[C:10]([CH2:11][CH3:12])[N:8]=[C:7]2[N:3]([CH2:1][CH3:2])[N:4]=[CH:5][C:6]=12

参加物

6

反応物 4

HCID 8471TriethylamineHCID 24813Phosphorus oxychlorideHCID 3373101-Ethyl-1H-pyrazol-5-amineHCID 57819400Diethyl(1-chloropropylidene)propanedioate

生成物 1

HCID 59683218Ethyl 4-chloro-1,6-diethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate収率 93.3%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

反応条件

温度
110 °C

実験手順

To 1-ethyl-1H-pyrazol-5-amine (Aldrich, 1.52 g, 13.7 mmol) was added a solution of diethyl (1-chloropropylidene)propanedioate (3.21 g, 13.7 mmol) in toluene (40 mL) followed by triethylamine (3.78 mL, 27.3 mmol) and then heated at reflux for 6 h. The cooled mixture was concentrated to dryness and the resulting brown residue was treated with phosphorus oxychloride (25 mL, 0.274 mol) and heated to 110° C. for 17.5 h. The cooled mixture was concentrated to dryness and the residue was to water (caution, exotherm) and extracted with ethyl acetate. The aqueous phase was treated with aqueous sodium hydroxide (2M) to achieve pH 9 and extracted with additional ethyl acetate. The combined organics were washed with aqueous sodium bicarbonate, then brine, dried and concentrated to dryness to afford 3.6 g of a dark brown oil. The product was purified by flash chromatography on silica (150 mL) eluting with ethyl acetate/cyclohexane from 1:10 to 1:8 to afford 1.8 g of the title compound. LC-MS m/z 282 (M+H)+, 3.46 min (ret time).

後処理

  1. temperatureheated
  2. temperatureat reflux for 6 h
  3. concentrationThe cooled mixture was concentrated to dryness
  4. concentrationThe cooled mixture was concentrated to dryness
  5. extractionextracted with ethyl acetate
  6. additionThe aqueous phase was treated with aqueous sodium hydroxide (2M)
  7. extractionextracted with additional ethyl acetate
  8. washThe combined organics were washed with aqueous sodium bicarbonate
  9. dry with materialbrine, dried
  10. concentrationconcentrated to dryness

出典と根拠

ORDレコード
ord-f611def7a04449bda16f84523ebaf393
出典データセット
uspto-grants-2011_11
特許番号
US08067408B2

反応ノート

読み込み中…