Acetic Acid → 6-[({1-[3-(7-methoxy-quinoxalin-2-yloxy)-propyl]-piperidin-4-ylmethyl}-amino)-methyl]-4H-pyrido[3,2-b][1,4]oxazin-3-one

HRID 1019871ノート

反応式

HRID 1019871 の反応式
[O:1]=[C:2]1[CH2:7][O:6][C:5]2[CH:8]=[CH:9][C:10]([CH:12]=O)=[N:11][C:4]=2[NH:3]1.[CH3:14][O:15][C:16]1[CH:25]=[C:24]2[C:19]([N:20]=[CH:21][C:22]([O:26][CH2:27][CH2:28][CH2:29][N:30]3[CH2:35][CH2:34][CH:33]([CH2:36][NH2:37])[CH2:32][CH2:31]3)=[N:23]2)=[CH:18][CH:17]=1.C(O)(=O)C.C([BH3-])#N.[Na+]>ClCCCl.CO>[CH3:14][O:15][C:16]1[CH:25]=[C:24]2[C:19]([N:20]=[CH:21][C:22]([O:26][CH2:27][CH2:28][CH2:29][N:30]3[CH2:31][CH2:32][CH:33]([CH2:36][NH:37][CH2:12][C:10]4[CH:9]=[CH:8][C:5]5[O:6][CH2:7][C:2](=[O:1])[NH:3][C:4]=5[N:11]=4)[CH2:34][CH2:35]3)=[N:23]2)=[CH:18][CH:17]=1

参加物

7

反応物 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 218737373-Oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-carbaldehydeHCID 66746562C-{1-[3-(7-methoxy-quinoxalin-2-yloxy)-propyl]-piperidin-4-yl}-methylamine

生成物 1

HCID 468520736-[({1-[3-(7-methoxy-quinoxalin-2-yloxy)-propyl]-piperidin-4-ylmethyl}-amino)-methyl]-4H-pyrido[3,2-b][1,4]oxazin-3-one収率 30.5%

試薬・触媒・溶媒 2

HCID 111,2-Dichloroethane溶媒HCID 887Methanol溶媒

実験手順

3-Oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-carbaldehyde (22 mg, 0.12 mmol 1.0 eq) is added at room temperature to a stirred solution of C-{1-[3-(7-methoxy-quinoxalin-2-yloxy)-propyl]-piperidin-4-yl}-methylamine (40 mg, 0.12 mmol, 1.0 eq) in 1,2-dichloroethane (2 mL) and methanol (0.5 mL), followed by acetic acid (9 μL, 0.15 mmol, 1.3 eq) and sodium cyanoborohydride (11 mg, 0.15 mmol, 1.3 eq). After 15 hours stirring at room temperature, the reaction mixture is extracted with dichloromethane (3×5 mL) and a saturated sodium hydrogen carbonate aqueous solution (5 mL). The combined organic layers are dried over sodium sulfate, filtered and concentrated to give a residue that is purified by preparative HPLC to afford 6-[({1-[3-(7-methoxy-quinoxalin-2-yloxy)-propyl]-piperidin-4-ylmethyl}-amino)-methyl]-4H-pyrido[3,2-b][1,4]oxazin-3-one as a white viscous oil (18 mg, 29% yield).

後処理

  1. extractionthe reaction mixture is extracted with dichloromethane (3×5 mL)
  2. dry with materialThe combined organic layers are dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give a residue that
  6. customis purified by preparative HPLC

出典と根拠

ORDレコード
ord-8e0f1e7c4d3e4b329d349ad46218e071
出典データセット
uspto-grants-2014_05
特許番号
US08716280B2

反応ノート

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