Diisopropylethylamine → 6-[4-[4-[3-(4-Acetylpiperazin-1-yl)propoxy]phenyl]piperidin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine

HRID 2381090

반응식

HRID 2381090 반응식
CCN(C(C)C)C(C)C.Cl[C:11]1[CH:12]=[CH:13][C:14]2[N:15]([C:17]([C:20]([F:23])([F:22])[F:21])=[N:18][N:19]=2)[N:16]=1.[C:24]([N:27]1[CH2:32][CH2:31][N:30]([CH2:33][CH2:34][CH2:35][O:36][C:37]2[CH:42]=[CH:41][C:40]([CH:43]3[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]3)=[CH:39][CH:38]=2)[CH2:29][CH2:28]1)(=[O:26])[CH3:25]>CN(C=O)C>[C:24]([N:27]1[CH2:32][CH2:31][N:30]([CH2:33][CH2:34][CH2:35][O:36][C:37]2[CH:38]=[CH:39][C:40]([CH:43]3[CH2:48][CH2:47][N:46]([C:11]4[CH:12]=[CH:13][C:14]5[N:15]([C:17]([C:20]([F:23])([F:22])[F:21])=[N:18][N:19]=5)[N:16]=4)[CH2:45][CH2:44]3)=[CH:41][CH:42]=2)[CH2:29][CH2:28]1)(=[O:26])[CH3:25]

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 6136576-Chloro-3-(trifluoromethyl)-(1,2,4)triazolo(4,3-b)pyridazineHCID 685041394-[4-[3-(4-Acetylpiperazin-1-yl)propoxy]phenyl]piperidine

생성물 1

HCID 591496936-[4-[4-[3-(4-Acetylpiperazin-1-yl)propoxy]phenyl]piperidin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine수율 95.4%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
80 °C

실험 절차

DIPEA (5.21 mL, 29.93 mmol) was added to 6-chloro-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazine (obtained as described in Monatsh. Chem. 1972, 103, 1591) (6.06 g, 27.21 mmol) and 4-[4-[3-(4-acetylpiperazin-1-yl)propoxy]phenyl]piperidine (9.40 g, 27.21 mmol) in DMF (200 mL). The resulting solution was stirred at 80° C. for 1 hour. The reaction mixture was cooled to room temperature then evaporated to dryness. Water (600 mL) was then added and the mixture extracted with DCM (2×600 mL). The combined organic layers were dried (Na2SO4), filtered and concentrated under reduced pressure. The crude product was purified by flash silica chromatography, elution gradient 0 to 10% MeOH in DCM. Pure fractions were evaporated to dryness to afford 6-[4-[4-[3-(4-acetylpiperazin-1-yl)propoxy]phenyl]piperidin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine (13.80 g, 95%) as an orange solid.

후처리

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customthen evaporated to dryness
  3. additionWater (600 mL) was then added
  4. extractionthe mixture extracted with DCM (2×600 mL)
  5. dry with materialThe combined organic layers were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 10% MeOH in DCM
  9. customPure fractions were evaporated to dryness

출처 및 근거

ORD 기록
ord-63517275c6a94442bc0cdb76092be245
출처 데이터셋
uspto-grants-2012_09
특허 번호
US08258140B2

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