HCID 178490955, 화합물 → HCID 178511616, 화합물
반응식
[NH2:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][C:9]2[CH:10]=[C:11]([N:28]([CH:38]3[CH2:40][CH2:39]3)CC3C=CC(OC)=CC=3)[C:12]3[N:13]([C:15]([C:18]([NH:20][C:21]4[CH:26]=[CH:25][N:24]=[C:23]([F:27])[CH:22]=4)=[O:19])=[CH:16][N:17]=3)[N:14]=2)[CH2:4][CH2:3]1>C(O)(C(F)(F)F)=O>[NH2:1][C@H:2]1[CH2:3][CH2:4][C@H:5]([NH:8][C:9]2[CH:10]=[C:11]([NH:28][CH:38]3[CH2:39][CH2:40]3)[C:12]3[N:13]([C:15]([C:18]([NH:20][C:21]4[CH:26]=[CH:25][N:24]=[C:23]([F:27])[CH:22]=4)=[O:19])=[CH:16][N:17]=3)[N:14]=2)[CH2:6][CH2:7]1참가 물질
반응 조건
- 온도
- 70 °C
실험 절차
6-((trans)-4-aminocyclohexylamino)-8-(cyclopropyl(4-methoxybenzyl)amino)-N-(2-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide (25B) was dissolved in TFA (2 mL) and heated at 70° C. for 2 hrs. The reaction mixture was concentrated and purified by HPLC (Phenomenex Axia Luna 5 micron 30×100 mm) 20% B (Solvent B=90% MeOH-10% H2O-0.1% TFA) to 100% B in A (Solvent A=10% MeOH-90% H2O-0.1% TFA) to afford 6-((trans)-4-aminocyclohexylamino)-8-(cyclopropylamino)-N-(2-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide (23 mg, 43.2% yield) as a 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=1.448 minutes. [M+H]=425.29. 1H NMR (400 MHz, MeOD) δ ppm 8.08-8.26 (1H, m), 8.04 (1H, s), 7.60-7.74 (1H, m), 7.29-7.45 (1H, m), 5.99-6.16 (1H, m), 3.61-3.92 (1H, m), 3.08-3.28 (1H, m), 2.48-2.69 (1H, m), 2.26-2.48 (2H, m), 2.07-2.28 (2H, m), 1.37-1.69 (4H, m), 0.79-1.00 (2H, m), 0.53-0.76 (2H, m).
후처리
- concentrationThe reaction mixture was concentrated
- custompurified by HPLC (Phenomenex Axia Luna 5 micron 30×100 mm) 20% B (Solvent B=90% MeOH-10% H2O-0.1% TFA) to 100% B in A (Solvent A=10% MeOH-90% H2O-0.1% TFA)
출처 및 근거
- ORD 기록
- ord-833543f450c74901a66df44e6c0fe75d
- 출처 데이터셋
- uspto-grants-2013_03
- 특허 번호
- US08389527B2
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