tert-Butyl 4-carbamothioylpiperazine-1-carboxylate → 4-(2,4-Difluorophenyl)-5-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-2-(piperazin-1-yl)thiazole

HRID 1930027노트

반응식

HRID 1930027 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.[C:25]([N:28]1[CH2:33][CH2:32][N:31](C(OC(C)(C)C)=O)[CH2:30][CH2:29]1)(=[S:27])[NH2:26]>CCO>[F:12][C:6]1[CH:7]=[C:8]([F:11])[CH:9]=[CH:10][C:5]=1[C:3]1[N:26]=[C:25]([N:28]2[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)[S:27][C:2]=1[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

참가 물질

4

반응물 2

HCID 12093220tert-Butyl 4-carbamothioylpiperazine-1-carboxylateHCID 579298612-Bromo-1-(2,4-difluorophenyl)-2-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)ethanone

생성물 1

HCID 579299074-(2,4-Difluorophenyl)-5-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-2-(piperazin-1-yl)thiazole수율 10%

시약·촉매·용매 1

HCID 702Ethanol용매

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, 1.5 mmol; Preparation #A.2) and tert-butyl 4-carbamothioylpiperazine-1-carboxylate (Beta Pharma Inc, 0.341 g, 1.39 mmol) in EtOH (3 mL) was heated to reflux overnight. After cooling to ambient temperature, the crude mixture was partitioned between DCM and 1N aqueous HCl. The aqueous layer was basified with saturated aqueous Na2CO3 and extracted with DCM. The organics were dried over MgSO4, filtered, concentrated under reduced pressure, and purified by silica gel chromatography using DCM/MeOH (linear gradient, 100:0 to 90:10) to give the title compound (0.061 g, 10%): LC/MS (Table 1, Method a) Rt=2.31 min; MS m/z: 442.8 (M+H)+.

후처리

  1. temperaturewas heated
  2. temperatureto reflux overnight
  3. customthe crude mixture was partitioned between DCM and 1N aqueous HCl
  4. extractionextracted with DCM
  5. dry with materialThe organics were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. custompurified by silica gel chromatography

출처 및 근거

ORD 기록
ord-98f1b5fe6d5f4c929f8174b44a61e009
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08188083B2

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