Dimethylformamide → 2-(3-Hydroxypiperidino)-8-[(E)-2-(4-isopropyl-1,3-thiazol-2-yl)-1-ethenyl]-4H-pyrido[1,2-a]pyrimidin-4-one

HRID 1828488Notes

Reaction equation

HRID 1828488 reaction equation
O[C:2]1[N:3]=[C:4]2[CH:12]=[C:11](/[CH:13]=[CH:14]/[C:15]3[S:16][CH:17]=[C:18]([CH:20]([CH3:22])[CH3:21])[N:19]=3)[CH:10]=[CH:9][N:5]2[C:6](=[O:8])[CH:7]=1.CN(C)C=O.C1(C)C=CC(S(Cl)(=O)=O)=CC=1.[OH:39][CH:40]1[CH2:45][CH2:44][CH2:43][NH:42][CH2:41]1>O1CCCC1.CN(C)C1C=CN=CC=1>[OH:39][CH:40]1[CH2:45][CH2:44][CH2:43][N:42]([C:2]2[N:3]=[C:4]3[CH:12]=[C:11](/[CH:13]=[CH:14]/[C:15]4[S:16][CH:17]=[C:18]([CH:20]([CH3:22])[CH3:21])[N:19]=4)[CH:10]=[CH:9][N:5]3[C:6](=[O:8])[CH:7]=2)[CH2:41]1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 73974-Toluenesulfonyl chlorideHCID 232933-Hydroxypiperidine2×HCID 1363468402-Hydroxy-8-[(E)-2-(4-isopropyl-1,3-thiazol-2-yl)-1-ethenyl]-4H-pyrido[1,2-a]pyrimidin-4-one2×

Product 1

HCID 865881182-(3-Hydroxypiperidino)-8-[(E)-2-(4-isopropyl-1,3-thiazol-2-yl)-1-ethenyl]-4H-pyrido[1,2-a]pyrimidin-4-oneYield 68.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

The 2-hydroxy-8-[(E)-2-(4-isopropyl-1,3-thiazol-2-yl)-1-ethenyl]-4H-pyrido[1,2-a]-pyrimidin-4-one (1.00 g, 3.19 mmol) obtained in (E) was dissolved in anhydrous tetrahydrofuran (15.0 ml) and anhydrous dimethylformamide (15.0 ml), added with 4-dimethylaminopyridine (585 mg, 4.79 mmol) and p-toluenesulfonyl chloride (730 mg, 3.83 mmol), and then the mixture was stirred at room temperature for 50 minutes. Subsequently, the reaction solution was added with 3-hydroxypiperidine (646 mg, 6.38 mmol) and stirred at room temperature for 16 hours, and then added with 3-hydroxypiperidine (968 mg, 9.57 mmol) and stirred at 60° C. for 1.5 hours. After the reaction mixture was concentrated, the residue was purified by silica gel column chromatography (chloroform:methanol=100:0→100:1→100:2→100:5→100:10, v/v) to obtain the title compound (865 mg, 68%).

Workup

  1. stirringstirred at room temperature for 16 hours
  2. stirringstirred at 60° C. for 1.5 hours
  3. concentrationAfter the reaction mixture was concentrated
  4. customthe residue was purified by silica gel column chromatography (chloroform

Sources & evidence

ORD record
ord-4f8d8bee972b4444af08ee0776701987
Source dataset
uspto-grants-2006_06
Patent number
US07056917B2

Reaction notes

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