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Diisopropylethylamine → 6-((1-(3-Fluoro-5-(trifluoromethyl)benzyl)piperidin-4-yl)amino)pyridazine-3-carbonitrile

HRID 1258157
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HRID 1258157 반응식
Cl[C:2]1[N:7]=[N:6][C:5]([C:8]#[N:9])=[CH:4][CH:3]=1.[F:10][C:11]1[CH:12]=[C:13]([CH:22]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:24]=1)[CH2:14][N:15]1[CH2:20][CH2:19][CH:18]([NH2:21])[CH2:17][CH2:16]1.C(N(C(C)C)CC)(C)C>C(#N)C.ClCCl>[F:10][C:11]1[CH:12]=[C:13]([CH:22]=[C:23]([C:25]([F:28])([F:26])[F:27])[CH:24]=1)[CH2:14][N:15]1[CH2:20][CH2:19][CH:18]([NH:21][C:2]2[N:7]=[N:6][C:5]([C:8]#[N:9])=[CH:4][CH:3]=2)[CH2:17][CH2:16]1
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참가 물질

6

반응물 3

HCID 81531DiisopropylethylamineHCID 133828716-Chloropyridazine-3-carbonitrileHCID 532561571-(3-Fluoro-5-trifluoromethyl-benzyl)-piperidin-4-ylamine

생성물 1

HCID 249891986-((1-(3-Fluoro-5-(trifluoromethyl)benzyl)piperidin-4-yl)amino)pyridazine-3-carbonitrile수율 80.5%

시약·촉매·용매 2

HCID 6342Acetonitrile용매
HCID 6344
Dichloromethane
용매

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온도
120 °C

실험 절차

A mixture of 6-chloro-pyridazine-3-carbonitrile (D4) (1.39 g, 9.95 mmol), 1-(3-fluoro-5-trifluoromethyl-benzyl)-piperidin-4-ylamine (D7) (2.5 g, 9.04 mmol) and diisopropylethylamine (2.63 ml, 14.92 mmol) in acetonitrile (2 ml) was stirred at 120° C. for 30 min, under microwave irradiation ((Biotage MW-oven). The mixture was then diluted with dichloromethane (50 ml) and extracted with a saturated solution of sodium carbonate. The organic layer was separated, dried (Na2SO4), filtered, evaporated in vacuo and the residue purified by column chromatography (silica gel; 0-2.5% ammonia in methanol (7M)/dichloromethane). The desired fractions were collected and evaporated in vacuo. The residue precipitated from diisopropylether to yield E17 (2.76 g, 73%) as a solid. C18H17F4N5 requires 379. Found 380 (MH+); mp: 151.4° C.

후처리

  1. extractionextracted with a saturated solution of sodium carbonate
  2. customThe organic layer was separated
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customthe residue purified by column chromatography (silica gel; 0-2.5% ammonia in methanol (7M)/dichloromethane)
  7. customThe desired fractions were collected
  8. customevaporated in vacuo
  9. customThe residue precipitated from diisopropylether

출처 및 근거

ORD 기록
ord-1ba884f371b745969ada46dcb27749b5
출처 데이터셋
uspto-grants-2013_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08466153B2

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