Trifluoroacetic acid → 2-(2-methyl-3-(piperidin-4-ylamino)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

HRID 1055884ノート

反応式

HRID 1055884 の反応式
[CH3:1][C:2]1[C:3]([NH:22][CH:23]2[CH2:28][CH2:27][N:26](C(OC(C)(C)C)=O)[CH2:25][CH2:24]2)=[N:4][C:5]2[C:10]([N:11]=1)=[CH:9][CH:8]=[CH:7][C:6]=2[C:12]1[NH:20][C:19]2[CH2:18][CH2:17][NH:16][C:15](=[O:21])[C:14]=2[CH:13]=1.C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH3:1][C:2]1[C:3]([NH:22][CH:23]2[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)=[N:4][C:5]2[C:10](=[CH:9][CH:8]=[CH:7][C:6]=2[C:12]2[NH:20][C:19]3[CH2:18][CH2:17][NH:16][C:15](=[O:21])[C:14]=3[CH:13]=2)[N:11]=1

参加物

5

反応物 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 89793635tert-butyl 4-((3-methyl-8-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)quinoxalin-2-yl)amino)piperidine-1-carboxylate

生成物 1

HCID 897834662-(2-methyl-3-(piperidin-4-ylamino)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one収率 6.8%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

A solution of tert-butyl 4-((3-methyl-8-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)quinoxalin-2-yl)amino)piperidine-1-carboxylate (Ex. 47, 80 mg, 0.168 mmol) in DCM (1.7 mL) was stirred at 25° C. before adding TFA (12.47 μl, 0.168 mmol, Sigma Aldrich). The resulting solution was stirred for 30 min before carefully adding saturated aq. NaHCO3 (10 mL) and stirring for an additional 30 min. The reaction mixture was then concentrating under reduced pressure, and the residue was taken up in DMSO and purified by reverse-phase preparative HPLC (Phenomenex Gemini column, 10 micron, C18, 100 Å, 150×30 mm, 0.1% TFA in ACN/H2O, gradient 5% to 80%). The product-containing fractions were concentrated under reduced pressure, and the residue was loaded onto a pre-washed (MeOH, 1 volume) functionalized Si-carbonate column (Silicyle) and allowed to percolate through, providing 2-(2-methyl-3-(piperidin-4-ylamino)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (4.3 mg, 6.8%). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.92 (1H, s) 7.83-7.91 (1H, m) 7.52-7.58 (2H, m) 7.28-7.35 (1H, m) 7.11-7.16 (1H, m) 3.98-4.11 (3H, m) 3.41-3.49 (2H, m) 2.97-3.06 (2H, m) 2.89 (2H, s) 2.59-2.71 (2H, m) 2.54 (3H, s) 1.93-2.04 (2H, m) 1.43-1.59 (2H, m). m/z (ESI, +ve) 377.1 (M+H)+.

後処理

  1. concentrationThe reaction mixture was then concentrating under reduced pressure
  2. custompurified by reverse-phase preparative HPLC (Phenomenex Gemini column, 10 micron, C18, 100 Å, 150×30 mm, 0.1% TFA in ACN/H2O, gradient 5% to 80%)
  3. concentrationThe product-containing fractions were concentrated under reduced pressure
  4. washa pre-washed (MeOH, 1 volume) functionalized Si-carbonate column (Silicyle)

出典と根拠

ORDレコード
ord-043b9d277f1a44a8a6392e26ad46e03b
出典データセット
uspto-grants-2016_07
特許番号
US09394297B2

反応ノート

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