Ammonia → 8-(2-bromobenzyl)-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one

HRID 1188713Notes

Reaction equation

HRID 1188713 reaction equation
[H-].[Na+].[CH3:3][S:4][C:5]1[N:6]=[CH:7][C:8]2[CH:14]=[CH:13][C:12](=[O:15])[NH:11][C:9]=2[N:10]=1.N.[Br:17][C:18]1[CH:25]=[CH:24][CH:23]=[CH:22][C:19]=1[CH2:20]Br>CN(C)C=O.C(OCC)(=O)C.[Cl-].[Na+].O>[Br:17][C:18]1[CH:25]=[CH:24][CH:23]=[CH:22][C:19]=1[CH2:20][N:11]1[C:9]2[N:10]=[C:5]([S:4][CH3:3])[N:6]=[CH:7][C:8]=2[CH:14]=[CH:13][C:12]1=[O:15]

Participants

8

Reactant 4

HCID 222AmmoniaHCID 24758Sodium hydrideHCID 769652-Bromobenzyl bromideHCID 12347632-(methylthio)pyrido(2,3-d)pyrimidin-7(8H)-one

Product 1

HCID 667614708-(2-bromobenzyl)-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
60 °C

Procedure

To a suspension of NaH (60%, 47 mg, 1.19 mmol) in anhydrous dimethylformamide (2 mL) was added 2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one (150 mg, 0.78 mmol, prepared by the method in example 1, Steps 1-5, using ammonia in the first step) at room temperature and stirred at 60° C. for 0.5 h. The reaction mixture was cooled down to room temperature and 2-bromobenzyl bromide was added and stirred for 48 h. The mixture was diluted with ethyl acetate (20 mL) and 10% brine solution (10 mL), the two phases were separated, the aqueous layer was washed with ethyl acetate (1×20 mL), the combined organic layer was dried over sodium sulfate, filtered and evaporated to give 8-(2-bromobenzyl)-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one, an orange oil (0.24 g, 0.66 mmol, 84%). ESMS m/z 362 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 8.63 (s, 1H), 7.69 (d, J=9.5 Hz, 1H), 7.59 (dd, J=7.4, 1.4 Hz, 1H), 7.05-7.15 (m, 2H), 6.74 (d, J=9.5 Hz, 1H), 6.65 (d, J=7.0 Hz, 1H), 5.69 (s, 2H), 2.38 (s, 3H).

Workup

  1. customprepared by the method in example 1, Steps 1-5
  2. customat room temperature
  3. temperatureThe reaction mixture was cooled down to room temperature
  4. stirringstirred for 48 h
  5. customthe two phases were separated
  6. washthe aqueous layer was washed with ethyl acetate (1×20 mL)
  7. dry with materialthe combined organic layer was dried over sodium sulfate
  8. filtrationfiltered
  9. customevaporated

Sources & evidence

ORD record
ord-a922e54c3e9c48129b6129e291a43984
Source dataset
uspto-grants-2014_03
Patent number
US08674095B2

Reaction notes

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