Trifluoroacetic acid → HCID 178522326, 화합물

HRID 1943442노트

반응식

HRID 1943442 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.CCN(C(C)C)C(C)C.[C:50]1([S:56](Cl)(=[O:58])=[O:57])[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH:38]1([NH:28][C:11]2[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]=[C:9]([NH:8][C@H:5]3[CH2:4][CH2:3][C@H:2]([NH:1][S:56]([C:50]4[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=4)(=[O:58])=[O:57])[CH2:7][CH2:6]3)[CH:10]=2)[CH2:39][CH2:40]1

참가 물질

6

반응물 4

HCID 6422Trifluoroacetic acidHCID 7369Benzenesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 178490955HCID 178490955, 화합물

생성물 1

HCID 178522326HCID 178522326, 화합물수율 54.2%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of 6-((trans)-4-aminocyclohexylamino)-8-(cyclopropyl(4-methoxybenzyl)amino)-N-(2-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide (20.00 mg, 0.037 mmol) in CH2Cl2 (1 mL) was added DIEA (0.00617 mL, 0.035 mmol) and benzenesulfonyl chloride (1.5 mg, 8.49 μmol). The reaction solution was stirred at room temperature for 30 min, concentrated and then treated with TFA (1.132 mL, 14.69 mmol) at 70° C. for 1 hr. The reaction mixture was concentrated and purified by HPLC (Phenomenex Axia Luna 5 micron 30×100 mm) 30% 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 isolate the title compound, 8-(cyclopropylamino)-N-(2-fluoropyridin-4-yl)-6-((trans)-4-(phenylsulfonamido)cyclohexylamino)imidazo[1,2-b]pyridazine-3-carboxamide (2.6 mg, 12.54% yield) as a white solid (13.0 mg, 44.4%). 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=1.910 minutes. [M+H]=565.25. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.36-11.55 (1H, m), 8.13-8.33 (1H, m), 7.89-8.01 (1H, m), 7.76-7.91 (3H, m), 7.47-7.70 (5H, m), 7.20-7.38 (1H, m), 6.78-6.96 (1H, m), 5.83-6.02 (1H, m), 3.48-3.72 (1H, m), 2.92-3.13 (1H, m), 1.83-2.12 (2H, m), 1.53-1.80 (2H, m), 0.99-1.41 (5H, m), 0.66-0.85 (2 H, m), 0.41-0.67 (2H, m), 1.80-2.05 (2H, m), 1.39-1.70 (2H, m), 1.14-1.41 (2H, m), 0.77 (2H, d, J=4.77 Hz), 0.63 (2H, d, J=3.01 Hz).

후처리

  1. concentrationconcentrated
  2. concentrationThe reaction mixture was concentrated
  3. custompurified by HPLC (Phenomenex Axia Luna 5 micron 30×100 mm) 30% 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-7798a470556c45e9bfaa6ec2566185d6
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08389527B2

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