6-chloro-N-(2-chloropyridin-4-yl)-8-(cyclopropyl(4-methoxybenzyl)amino)imidazo[1,2-b]pyridazine-3-carboxamide → HCID 178490954, 화합물

HRID 1943434

반응식

HRID 1943434 반응식
Cl[C:2]1[CH:3]=[C:4]([N:21]([CH:31]2[CH2:33][CH2:32]2)[CH2:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)[C:5]2[N:6]([C:8]([C:11]([NH:13][C:14]3[CH:19]=[CH:18][N:17]=[C:16]([Cl:20])[CH:15]=3)=[O:12])=[CH:9][N:10]=2)[N:7]=1.[NH2:34][C@H:35]1[CH2:40][CH2:39][C@H:38]([NH2:41])[CH2:37][CH2:36]1>CN1CCCC1=O.O>[NH2:34][C@H:35]1[CH2:40][CH2:39][C@H:38]([NH:41][C:2]2[CH:3]=[C:4]([N:21]([CH:31]3[CH2:33][CH2:32]3)[CH2:22][C:23]3[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=3)[C:5]3[N:6]([C:8]([C:11]([NH:13][C:14]4[CH:19]=[CH:18][N:17]=[C:16]([Cl:20])[CH:15]=4)=[O:12])=[CH:9][N:10]=3)[N:7]=2)[CH2:37][CH2:36]1

참가 물질

5

반응물 2

HCID 596248746-chloro-N-(2-chloropyridin-4-yl)-8-(cyclopropyl(4-methoxybenzyl)amino)imidazo[1,2-b]pyridazine-3-carboxamideHCID 178511674HCID 178511674, 화합물

생성물 1

HCID 178490954HCID 178490954, 화합물수율 98%

시약·촉매·용매 2

HCID 962Water용매2회HCID 13387N-methyl-2-pyrrolidone용매

반응 조건

온도
120 °C

실험 절차

6-chloro-N-(2-chloropyridin-4-yl)-8-(cyclopropyl(4-methoxybenzyl)amino)imidazo[1,2-b]pyridazine-3-carboxamide (9 g, 18.6 mmol) was combined with trans-1,4-diaminocyclohexane (31.9 g, 279 mmol) in N-methyl-2-pyrrolidinone (50 mL) and heated at 80° C. for 16 hours and at 120° C. for 6 hrs. The reaction was cooled to room temperature, and water (200 mL) was added, and the solid collected via Buchner filtration. The crude product was purified with silica gel chromatography using a stepwise gradient of 10% methanol/chloroform to 25% methanol/chloroform/1% triethylamine to isolated foamy solid. The solid was suspended in water (400 mL) and collected with Buchner filtration (2×50 mL water wash) and dried for 16 hrs under reduced pressure to afford 6-((trans)-4-aminocyclohexylamino)-N-(2-chloropyridin-4-yl)-8-(cyclopropyl(4-methoxybenzyl)amino)imidazo[1,2-b]pyridazine-3-carboxamide (10.2 g, 18.18 mmol, 98% yield) as a off white solid. LC/MS (Phenomenex Luna 5 micron C18 4.6×30 mm, 0 to 100 B in 2 min with 1 min hold time, Flow rate=5 mL/min, detection at 254 nm, Solvent A: 10% methanol/90% water/0.1% TFA; Solvent B: 10% water/90% methanol/0.1% TFA) Rt=1.77 minutes. [M+H]=561.16.

후처리

  1. temperatureThe reaction was cooled to room temperature
  2. filtrationthe solid collected via Buchner filtration
  3. customThe crude product was purified with silica gel chromatography
  4. customto isolated foamy solid
  5. filtrationcollected with Buchner filtration (2×50 mL water wash)
  6. customdried for 16 hrs under reduced pressure

출처 및 근거

ORD 기록
ord-116d2d75317e4f3e887cf504bdbaf803
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08389527B2

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