3-Hydroxypiperidine → N8-(4-Cyclobutyl-1,3-thiazol-2-yl)-2-(3-hydroxypiperidino)-4-oxo-4H-pyrido-[1,2-a]pyrimidine-8-carboxamide

HRID 1828446ノート

反応式

HRID 1828446 の反応式
[CH:1]1([C:5]2[N:6]=[C:7]([NH:10][C:11]([C:13]3[CH:24]=[CH:23][N:16]4[C:17](=[O:22])[CH2:18][C:19](=O)[N:20]=[C:15]4[CH:14]=3)=[O:12])[S:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.P(Cl)(OC1C=CC=CC=1)(OC1C=CC=CC=1)=O.C(N(C(C)C)CC)(C)C.[OH:51][CH:52]1[CH2:57][CH2:56][CH2:55][NH:54][CH2:53]1.C(=O)([O-])O.[Na+]>CN(C)C=O.C(#N)C>[CH:1]1([C:5]2[N:6]=[C:7]([NH:10][C:11]([C:13]3[CH:24]=[CH:23][N:16]4[C:17](=[O:22])[CH:18]=[C:19]([N:54]5[CH2:55][CH2:56][CH2:57][CH:52]([OH:51])[CH2:53]5)[N:20]=[C:15]4[CH:14]=3)=[O:12])[S:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1

参加物

8

反応物 5

HCID 232933-Hydroxypiperidine3 回HCID 75654Diphenyl chlorophosphateHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 22063633N8-(4-cyclobutyl-1,3-thiazol-2-yl)-2,4-dioxo-3,4-dihydro-2H-pyrido[1,2-a]pyrimidine-8-carboxamide

生成物 1

HCID 22063638N8-(4-Cyclobutyl-1,3-thiazol-2-yl)-2-(3-hydroxypiperidino)-4-oxo-4H-pyrido-[1,2-a]pyrimidine-8-carboxamide収率 69%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6342Acetonitrile溶媒

反応条件

温度
-10 °C

実験手順

N8-(4-Cyclobutyl-1,3-thiazol-2-yl)-2,4-dioxo-3,4-dihydro-2H-pyrido[1,2-a]-pyrimidine-8-carboxamide (100 mg, 0.29 mmol) was added with acetonitrile (2 ml) and dimethylformamide (1 ml), cooled to −10° C. with ice, then added with diphenyl chlorophosphate (0.2 ml, 0.96 mmol), and further added dropwise with diisopropylethylamine (0.3 ml, 1.74 mmol). The reaction solution was stirred at −10° C. for 30 minutes, then added with 3-hydroxypiperidine (90 mg, 0.89 mmol), warmed to room temperature, and then further warmed to 80° C. As the reaction was not completed, the reaction solution was further added with 3-hydroxypiperidine (60 mg), stirred for 1 hour, and further added with 3-hydroxypiperidine (70 mg). After the disappear of the starting material was observed, the reaction was stopped with saturated aqueous sodium hydrogencarbonate, and the reaction solution was extracted with chloroform. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified by thin layer silica gel chromatography (chloroform:methanol=15:1) to obtain 85.2 mg (69%) of the title compound as yellow crystals.

後処理

  1. temperaturewarmed to room temperature
  2. temperaturefurther warmed to 80° C
  3. stirringstirred for 1 hour
  4. extractionthe reaction solution was extracted with chloroform
  5. dry with materialThe organic layer was dried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by thin layer silica gel chromatography (chloroform:methanol=15:1)

出典と根拠

ORDレコード
ord-3a4b0e553ea34acf8901b5749c05bcf4
出典データセット
uspto-grants-2006_06
特許番号
US07056917B2

反応ノート

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