Diethyl cyanophosphonate → 5-amino-6-chloro-2-ethyl-N-(piperidin-4-ylmethyl)imidazo[1,2-a]pyridine-8-carboxamide

HRID 1168253ノート

反応式

HRID 1168253 の反応式
[NH2:1][C:2]1[N:7]2[CH:8]=[C:9]([CH2:11][CH3:12])[N:10]=[C:6]2[C:5]([C:13]([OH:15])=O)=[CH:4][C:3]=1[Cl:16].[NH2:17][CH2:18][CH:19]1[CH2:24][CH2:23][N:22](C(OC(C)(C)C)=O)[CH2:21][CH2:20]1.P(C#N)(=O)(OCC)OCC.C(N(C(C)C)CC)(C)C>CN(C)C=O>[NH2:1][C:2]1[N:7]2[CH:8]=[C:9]([CH2:11][CH3:12])[N:10]=[C:6]2[C:5]([C:13]([NH:17][CH2:18][CH:19]2[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)=[O:15])=[CH:4][C:3]=1[Cl:16]

参加物

6

反応物 4

HCID 76257Diethyl cyanophosphonateHCID 81531DiisopropylethylamineHCID 7368171-Boc-4-(aminomethyl)piperidineHCID 222364965-Amino-6-chloro-2-ethylimidazo[1,2-a]pyridine-8-carboxylic acid

生成物 1

HCID 99496125-amino-6-chloro-2-ethyl-N-(piperidin-4-ylmethyl)imidazo[1,2-a]pyridine-8-carboxamide収率 90%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A mixture of 5-amino-6-chloro-2-ethylimidazo[1,2-a]pyridine-8-carboxylic acid (EXAMPLE 10, Step 2, 10.00 g, 41.72 mmol), tert-butyl 4-(aminomethyl)piperidine-1-carboxylate (J. Prugh, L. A. Birchenough and M. S. Egbertson, Synth. Commun., 1992, 22, 2357-60) (15.20 g, 70.93 mmol), diethyl phosphorocyanidate (10.76 mL, 70.93 mmol) and diisopropylethylamine (18.17 mL, 104.4 mmol) in N,N-dimethylformamide (267 mL) was stirred at room temperature for 43 h. The solvent was removed by evaporation. The residue was basified with aqueous sodium bicarbonate (40 mL), and extracted with dichloromethane (5×100 mL). The combined extract was washed with brine, dried over magnesium sulfate, and concentrated in vacuo. Flash chromatography of the residue eluting with dichloromethane/methanol (100:1 to 20:1) afforded 19.08 g (90%) of the title compound as a yellow oil.

後処理

  1. customThe solvent was removed by evaporation
  2. extractionextracted with dichloromethane (5×100 mL)
  3. extractionThe combined extract
  4. washwas washed with brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. washFlash chromatography of the residue eluting with dichloromethane/methanol (100:1 to 20:1)

出典と根拠

ORDレコード
ord-3d0e74c1d1c2417b8ded164c643c1665
出典データセット
uspto-grants-2003_09
特許番号
US06624162B2

反応ノート

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