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2-Fluoro-5-methylbenzoic acid → N-{4-[(2-aminoimidazo[1,2-b]pyridazin-6-yl)ethynyl]phenyl}-2-fluoro-5-methylbenzamide

HRID 589910
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HRID 589910 반응식
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[C:9][C:10]2[CH:11]=[CH:12][C:13]3[N:14]([CH:16]=[C:17]([NH2:19])[N:18]=3)[N:15]=2)=[CH:4][CH:3]=1.[F:20][C:21]1[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][C:22]=1[C:23](O)=[O:24].Cl.CN(C)CCCN=C=NCC>ClC(Cl)C.CN(C)C1C=CN=CC=1.C(Cl)(Cl)Cl>[NH2:19][C:17]1[N:18]=[C:13]2[CH:12]=[CH:11][C:10]([C:9]#[C:8][C:5]3[CH:6]=[CH:7][C:2]([NH:1][C:23](=[O:24])[C:22]4[CH:26]=[C:27]([CH3:30])[CH:28]=[CH:29][C:21]=4[F:20])=[CH:3][CH:4]=3)=[N:15][N:14]2[CH:16]=1
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참가 물질

7

반응물 3

HCID 2428292-Fluoro-5-methylbenzoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 1186384466-[(4-Aminophenyl)ethynyl]imidazo[1,2-b]pyridazin-2-amine

생성물 1

HCID 118638433N-{4-[(2-aminoimidazo[1,2-b]pyridazin-6-yl)ethynyl]phenyl}-2-fluoro-5-methylbenzamide

시약·촉매·용매 3

HCID 14284
4-(Dimethylamino)pyridine
촉매
HCID 6212Chloroform용매
HCID 63651,1-Dichloroethane용매

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온도
50 °C

실험 절차

To 6-[(4-aminophenyl)ethynyl]imidazo[1,2-b]pyridazin-2-amine, (30 mg, 0.12 mmol, 1 eq) and 2-fluoro-5-methylbenzoic acid (18.5 mg, 1 eq) in anhydrous dichloroethane (1 mL) under nitrogen atmosphere at room temperature was added 4-(dimethylamino)pyridine (2.94 mg, 0.2 eq) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (27.76 mg, 1.2 eq). After the reaction was stirred at 50° C. for 2 hours, it was diluted with chloroform, washed sequentially with aqueous ammonium chloride, saturated aqueous sodium bicarbonate, brine, and lastly dried with anhydrous sodium sulfate. The upper solution was decanted, concentrated, and the solid residue was subject to a gradient column chromatography (from CHCl3 to MeOH—CHCl3 1:25) to yield N-{4-[(2-aminoimidazo[1,2-b]pyridazin-6-yl)ethynyl]phenyl}-2-fluoro-5-methylbenzamide as a yellow solid in amount of 7 mg.

후처리

  1. washwashed sequentially with aqueous ammonium chloride, saturated aqueous sodium bicarbonate, brine
  2. dry with materiallastly dried with anhydrous sodium sulfate
  3. customThe upper solution was decanted
  4. concentrationconcentrated

출처 및 근거

ORD 기록
ord-537843567dc94088bfa61cd4ecc89104
출처 데이터셋
uspto-grants-2016_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09233968B1

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