Trifluoroacetic acid → HCID 178522326、化合物

HRID 1943442ノート

反応式

HRID 1943442 の反応式
[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

参加物

6

反応物 4

HCID 6422Trifluoroacetic acidHCID 7369Benzenesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 178490955HCID 178490955、化合物

生成物 1

HCID 178522326HCID 178522326、化合物収率 54.2%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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).

後処理

  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))

出典と根拠

ORDレコード
ord-7798a470556c45e9bfaa6ec2566185d6
出典データセット
uspto-grants-2013_03
特許番号
US08389527B2

反応ノート

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