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

HRID 1828446Notes

Reaction equation

HRID 1828446 reaction equation
[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

Participants

8

Reactant 5

HCID 232933-Hydroxypiperidine3×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

Product 1

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

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
-10 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-3a4b0e553ea34acf8901b5749c05bcf4
Source dataset
uspto-grants-2006_06
Patent number
US07056917B2

Reaction notes

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