(S)-3-Amino-1-benzylpiperidine → HCID 59624360、化合物

HRID 1943454ノート

反応式

HRID 1943454 の反応式
[CH2:1]([N:8]1[CH2:13][CH2:12][CH2:11][C@H:10]([NH2:14])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:16]1[CH:17]=[C:18]([NH:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][N:36]=2)[C:19]2[N:20]([C:22]([C:25]([NH:27][C:28]3[CH:33]=[CH:32][N:31]=[CH:30][CH:29]=3)=[O:26])=[CH:23][N:24]=2)[N:21]=1>CO.C(O)(C(F)(F)F)=O>[CH2:1]([N:8]1[CH2:13][CH2:12][CH2:11][C@H:10]([NH:14][C:16]2[CH:17]=[C:18]([NH:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][N:36]=3)[C:19]3[N:20]([C:22]([C:25]([NH:27][C:28]4[CH:29]=[CH:30][N:31]=[CH:32][CH:33]=4)=[O:26])=[CH:23][N:24]=3)[N:21]=2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

参加物

5

反応物 2

HCID 854131(S)-3-Amino-1-benzylpiperidineHCID 596246846-chloro-8-(pyridin-2-ylamino)-N-(pyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide

生成物 1

HCID 59624360HCID 59624360、化合物収率 7.1%

試薬・触媒・溶媒 2

HCID 6422Trifluoroacetic acid触媒HCID 887Methanol溶媒

反応条件

温度
170 °C

実験手順

A vial containing a mixture of (S)-1-benzylpiperidin-3-amine (0.385 g, 2.021 mmol) and 6-chloro-8-(pyridin-2-ylamino)-N-(pyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide 37A (0.08 g, 0.135 mmol) was heated to 170° C. overnight. The mixture was dissolved in 3 mL methanol and 3 mL Solvent B (90% MeOH, 10% water, 0.1% TFA). One drop of TFA was added to the solution, the sample was split into 4 equal volumes and purified by reverse phase preparative HPLC on a Phenx Luna Axia Column 5u (21.2×100 mm) Solvent A (10% MeOH, 90% water, 0.1% TFA), Solvent B (90% MeOH, 10% water, 0.1% TFA) 20-100% solvent B gradient, 20 mL/min, 220 nM UV detection to provide (S)-6-(1-benzylpiperidin-3-ylamino)-8-(pyridin-2-ylamino)-N-(pyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide (0.0082 g, 9.52 μmol, 7.06% yield). 1H NMR (500 MHz, CD3OD) δ ppm 8.42 (2H, m), 8.02-7.68 (5H, m), 7.49 (1H, m), 7.29-6.76 (9H, m), 4.2-3.95 (2H, m), 3.73-3.58 (1H, m), 3.37 (1H, m), 3.06-2.64 (2H, m), 2.32-1.78 (3H, m). LC/MS: HPLC Retention time: 2.15 min, MS: 520 (M+1) (Shimidazu LC, Waters Sunfire C-18 column (4.65×50 mm, 5 um, 0-100% Solvent B, 4 min gradient, 4 mL/min, 220 UV detection. Solvent A: 10% MeOH/90% Water/0.1% TFA, Solvent B 90% MeOH/10% Water/0.1% TFA.)

後処理

  1. additionA vial containing
  2. customthe sample was split into 4 equal volumes
  3. custompurified by reverse phase preparative HPLC on a Phenx Luna Axia Column 5u (21.2×100 mm) Solvent A (10% MeOH, 90% water, 0.1% TFA), Solvent B (90% MeOH, 10% water, 0.1% TFA) 20-100% solvent B gradient, 20 mL/min, 220 nM UV detection

出典と根拠

ORDレコード
ord-ddae8b537fd84f51a1220766a59961f9
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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