Azetidine-1-carbothiohydrazide → 6-(2-(2,4-Difluorophenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-3-yl)-3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazine

HRID 1930043노트

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HRID 1930043 반응식
Br[CH:2]([C:13]1[CH:14]=[CH:15][C:16]2[N:17]([C:19]([CH:22]([CH3:24])[CH3:23])=[N:20][N:21]=2)[N:18]=1)[C:3]([C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][C:6]=1[F:12])=O.[N:25]1([C:29](=S)[NH:30][NH2:31])[CH2:28][CH2:27][CH2:26]1>CC(O)=O>[F:12][C:6]1[CH:7]=[C:8]([F:11])[CH:9]=[CH:10][C:5]=1[C:3]1[C:2]([C:13]2[CH:14]=[CH:15][C:16]3[N:17]([C:19]([CH:22]([CH3:24])[CH3:23])=[N:20][N:21]=3)[N:18]=2)=[C:29]2[NH:25][CH2:26][CH2:27][CH2:28][N:30]2[N:31]=1

참가 물질

4

반응물 2

HCID 57929853Azetidine-1-carbothiohydrazideHCID 579298612-Bromo-1-(2,4-difluorophenyl)-2-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)ethanone

생성물 1

HCID 1361368236-(2-(2,4-Difluorophenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-3-yl)-3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazine수율 26.3%

시약·촉매·용매 1

HCID 176Acetic Acid용매

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온도
55 °C

실험 절차

A mixture of 2-bromo-1-(2,4-difluorophenyl)-2-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)ethanone (0.61 g, 1.54 mmol; Preparation #A.2) and azetidine-1-carbothiohydrazide (0.29 g, 2.20 mmol) in HOAc (5 mL) was stirred at about 55° C. for about 1-2 h. The reaction mixture was cooled to ambient temperature overnight and partitioned between DCM and water. The aqueous layer was basified with a saturated aqueous solution of Na2CO3 and extracted with DCM. The combined organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure. The resulting crude material was purified by chromatography on silica gel using DCM/MeOH (gradient, 100:0 to 90:10), stirred overnight with Et2O/DCM (100:10), and collected by vacuum filtration to give the title compound (0.16 g, 26%): LC/MS (Table 1, Method a) Rt=2.98 min; MS m/z: 396.2 (M+H)+; 1H NMR (CDCl3) δ 7.76 (d, J=9.89 Hz, 1H), 7.56-7.51 (m, 1H), 7.11-6.99 (m, 1H), 6.98-6.87 (m, 1H), 6.73 (dd, J=9.89, 1.83 Hz, 1H), 6.44 (s, 1H, broad), 4.2 (t, J=6.08 Hz, 2H), 3.61-3.58 (m, 2H), 3.56-3.52 (m, 1H), 2.36-2.24 (m, 2H), 1.58 (d, J=6.99 Hz, 6H).

후처리

  1. temperatureThe reaction mixture was cooled to ambient temperature overnight
  2. custompartitioned between DCM and water
  3. extractionextracted with DCM
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting crude material was purified by chromatography on silica gel
  8. stirringstirred overnight with Et2O/DCM (100:10)
  9. filtrationcollected by vacuum filtration

출처 및 근거

ORD 기록
ord-a02589ee6ffd48a9b3be3b86de0a3de5
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08188083B2

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