Water → Dimethylformamide

HRID 478739Notes

Reaction equation

HRID 478739 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][CH2:8][C:9]([O:11]CC)=O.[Li+].C[CH:16]([N-:18][CH:19](C)C)C.[N+:22]([C:25]1[CH:26]=[C:27]([NH:31][C:32]2[N:39]=[CH:38][CH:37]=[CH:36][C:33]=2[CH:34]=O)[CH:28]=[CH:29][CH:30]=1)([O-:24])=[O:23].[OH2:40]>C1COCC1>[N+:22]([C:25]1[CH:26]=[C:27]([N:31]2[C:32]3[C:33](=[CH:36][CH:37]=[CH:38][N:39]=3)[CH:34]=[C:8]([CH2:7][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)[C:9]2=[O:11])[CH:28]=[CH:29][CH:30]=1)([O-:24])=[O:23].[CH3:16][N:18]([CH:19]=[O:40])[CH3:2]

Participants

7

Reactant 4

HCID 962WaterHCID 347337Ethyl 3-(pyridin-2-yl)propanoateHCID 2724682Lithium diisopropylamideHCID 121149522-(3-Nitro-phenylamino)-pyridine-3-carbaldehyde

Product 2

HCID 6228DimethylformamideYield 67%HCID 120746181-(3-nitrophenyl)-3-(pyridin-2-ylmethyl)-1,8-naphthyridin-2(1H)-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Ethyl 3-(pyridin-2-yl)propionate (0.717 g, 2.0 eq., prepared in Synthetic Example 4) was dissolved in dry THF. To the solution was added LDA (2 ml of 2M solution, 2.0 eq.) at −78° C. or below in a methanol-dry ice bath under nitrogen atmosphere while stirring and the mixture was stirred for 1 hour. Next, to the reaction mixture was added dropwise a solution of 2-(3-nitrophenylamino)nicotinaldehyde (486 mg, 1.0 eq., prepared according to the procedure of Example 3 in JP, A, 62-228076 (1987)) in THF and the resultant mixture was stirred for 2 hours at −78° C. and then continued to stir for 24 hours until it reached room temperature. The reaction mixture was treated with water, and extracted with methylene chloride. The organic layer was dried, and evaporated. To the residue was added ethyl acetate to form crystals. The resulting crude crystals were subjected to recrystallization from DMF to give 1-(3-nitrophenyl)-3-(pyridin-2-ylmethyl)-1,8-naphthyridin-2(1H)-one, mp 229 to 231° C./DMF (yield 67%).

Workup

  1. stirringthe mixture was stirred for 1 hour
  2. customprepared
  3. stirringto stir for 24 hours until it
  4. customreached room temperature
  5. extractionextracted with methylene chloride
  6. customThe organic layer was dried
  7. customevaporated
  8. additionTo the residue was added ethyl acetate
  9. customto form crystals
  10. customThe resulting crude crystals were subjected to recrystallization from DMF

Sources & evidence

ORD record
ord-82160fa1ab234c4d88a1c75a2ef3f879
Source dataset
uspto-grants-2003_11
Patent number
US06642250B2

Reaction notes

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