Phosphorus oxychloride → 6-chloro-1-isopropyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid

HRID 1522331노트

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HRID 1522331 반응식
[CH3:1][CH:2]([N:4]1[C:8]2[NH:9][C:10](=O)[CH:11]=[C:12]([C:13]([OH:15])=[O:14])[C:7]=2[CH:6]=[N:5]1)[CH3:3].P(Cl)(Cl)([Cl:19])=O>>[Cl:19][C:10]1[CH:11]=[C:12]([C:13]([OH:15])=[O:14])[C:7]2[CH:6]=[N:5][N:4]([CH:2]([CH3:3])[CH3:1])[C:8]=2[N:9]=1

참가 물질

3

반응물 2

HCID 24813Phosphorus oxychlorideHCID 1363340421-Isopropyl-6-oxo-6,7-dihydro-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid

생성물 1

HCID 866776226-chloro-1-isopropyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid

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온도
105 °C

실험 절차

To a 75 mL pressure vessel was added 1-(1-methylethyl)-6-oxo-6,7-dihydro-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (4.12 g, 18.62 mmol), followed by phosphorous oxychloride (26.0 ml, 279 mmol). The flask was sealed and the stirring mixture heated at ca. 105° C. for ca. 18 h. After cooling to room temperature, the contents were concentrated in vacuo to remove most of volatiles. The residual contents were poured into a mixture of ice and 3M NaOH (60 mL), followed by additional 3M NaOH to ensure the pH stayed basic. The mixture was stirred for 30 min., and then cooled in an ice bath. The heterogenous mixture was slowly acidified to pH=3-4 with 6M HCl. The resulting suspension was extracted with EtOAc (3×). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo to afford a yellow solid which was dried in a hi-vac oven overnight. The title compound was collected as 4.11 g (90%), and used without further purification. LCMS E-S (M+H)=240.2/242.2. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.51 (d, J=6.57 Hz, 6 H) 5.17 (quin, J=6.63 Hz, 1 H) 7.65 (s, 1 H) 8.41 (s, 1 H) 14.25 (br. s., 1 H).

후처리

  1. customThe flask was sealed
  2. temperatureAfter cooling to room temperature
  3. concentrationthe contents were concentrated in vacuo
  4. customto remove most of volatiles
  5. additionThe residual contents were poured into a mixture of ice and 3M NaOH (60 mL)
  6. temperaturecooled in an ice bath
  7. extractionThe resulting suspension was extracted with EtOAc (3×)
  8. dry with materialThe combined organic layers were dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customto afford a yellow solid which
  12. customwas dried in a hi-vac oven overnight
  13. customThe title compound was collected as 4.11 g (90%)
  14. customused without further purification

출처 및 근거

ORD 기록
ord-5f68638d9c634cb087ae1559f7e6b48e
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09073924B2

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