2-Aminophenylboronic acid hydrochloride → 1-(4-chlorobutyl)-2-methyl-2H-pyrazolo[3,4-c]quinolin-4-amine hydrochloride

HRID 1360566

반응식

HRID 1360566 반응식
Br[C:2]1[C:3]([C:13]#[N:14])=[N:4][N:5]([CH3:12])[C:6]=1[CH2:7][CH2:8][CH2:9][CH2:10][Cl:11].Cl.[NH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1B(O)O>>[ClH:11].[Cl:11][CH2:10][CH2:9][CH2:8][CH2:7][C:6]1[N:5]([CH3:12])[N:4]=[C:3]2[C:2]=1[C:22]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[N:16]=[C:13]2[NH2:14]

참가 물질

3

반응물 2

HCID 164270902-Aminophenylboronic acid hydrochlorideHCID 669589924-bromo-5-(4-chlorobutyl)-1-methyl-1H-pyrazole-3-carbonitrile

생성물 1

HCID 669591321-(4-chlorobutyl)-2-methyl-2H-pyrazolo[3,4-c]quinolin-4-amine hydrochloride

반응 조건

온도
115 °C

실험 절차

The method described in Part F of Example 46 was used to couple 4-bromo-5-(4-chlorobutyl)-1-methyl-1H-pyrazole-3-carbonitrile (16.0 g, 60.0 mmol) and 2-aminophenylboronic acid hydrochloride (20.8 g, 0.120 mol). After the mixture was heated at 115° C. for 24 hours, it was cooled to ambient temperature and filtered through a plug of silica gel (eluting with 3:2 chloroform/methanol). The filtrate was concentrated under reduced pressure and dissolved in ethanol (300 mL). Hydrogen chloride (45 mL of a 4 M solution in ethanol) was added to the solution, and the reaction was heated at reflux for two hours and then cooled to ambient temperature. A precipitate formed and was isolated by filtration and washed with ethanol to provide 1-(4-chlorobutyl)-2-methyl-2H-pyrazolo[3,4-c]quinolin-4-amine hydrochloride. The filtrate was concentrated under reduced pressure and the resulting solid was dissolved in dichloromethane and water. The pH of the solution was raised to 14 using 50% aqueous NaOH while keeping the temperature at 0° C. by adding ice. The layers were separated, the aqueous layer was extracted with additional dichloromethane, the organic layers were combined, dried over Na2SO4, filtered and concentrated to a dark yellow oily solid. The residue was purified by chromatography using a HORIZON HPFC system (40+M cartridge, eluting with 0-30% CMA in chloroform) followed by recrystallization from acetonitrile to provide 1-(4-chlorobutyl)-2-methyl-2H-pyrazolo[3,4-c]quinolin-4-amine. This solid was purified as light tan crystals, mp 188-189° C.

후처리

  1. temperatureit was cooled to ambient temperature
  2. filtrationfiltered through a plug of silica gel (eluting with 3:2 chloroform/methanol)
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. dissolutiondissolved in ethanol (300 mL)
  5. additionHydrogen chloride (45 mL of a 4 M solution in ethanol) was added to the solution
  6. temperaturethe reaction was heated
  7. temperatureat reflux for two hours
  8. temperaturecooled to ambient temperature
  9. customA precipitate formed
  10. customwas isolated by filtration
  11. washwashed with ethanol

출처 및 근거

ORD 기록
ord-7221c8fdf99d44498b1953f33edf6e45
출처 데이터셋
uspto-grants-2011_02
특허 번호
US07879849B2

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