Sodium hydride → 2-{5-Phenyl-4-[(pyridin-2-ylmethyl)amino]thieno[2,3-d]pyrimidin-2-yl}malonic acid diethyl ester

HRID 910194Notes

Reaction equation

HRID 910194 reaction equation
[H-].[Na+].[CH2:3]([O:5][C:6](=[O:31])[CH2:7][C:8]1[N:9]=[C:10]([NH:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=2)[C:11]2[C:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[CH:15][S:14][C:12]=2[N:13]=1)[CH3:4]>C(=O)(OCC)OCC>[CH2:3]([O:5][C:6](=[O:31])[CH:7]([C:8]1[N:9]=[C:10]([NH:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=2)[C:11]2[C:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[CH:15][S:14][C:12]=2[N:13]=1)[C:6]([O:5][CH2:3][CH3:4])=[O:31])[CH3:4]

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 11711155(5-Phenyl-4-[(pyridin-2-ylmethyl)amino]thieno[2,3-d]pyrimidin-2-yl}acetic acid ethyl ester

Product 1

HCID 673819232-{5-Phenyl-4-[(pyridin-2-ylmethyl)amino]thieno[2,3-d]pyrimidin-2-yl}malonic acid diethyl esterYield 126.7%

Reagents, catalysts & solvents 1

HCID 7766Diethyl CarbonateSolvent

Procedure

Sodium hydride (60% dispersion in oil, 64 mg, 1.59 mmol) was treated with a solution of {5-phenyl-4-[(pyridin-2-ylmethyl)amino]thieno[2,3-d]pyrimidin-2-yl}acetic acid ethyl ester (0.43 g, 1.06 mmol) in diethyl carbonate (2.5 ml). The resulting suspension was stirred at ambient temperature for 5 hours and left to stand for 18 hours. The mixture was then quenched with aqueous ammonium chloride solution (50 ml) and extracted with diethyl ether (3×50 ml). The combined organic extracts were dried (MgSO4) and the solvent removed in vacuo to give the crude product. Purification by flash chromatography (silica) eluting with dichloromethane followed by dichloromethane and ethyl acetate (5:1) gave 2-{5-phenyl-4-[(pyridin-2-ylmethyl)amino]thieno[2,3-d]pyrimidin-2-yl}malonic acid diethyl ester as a colourless gum (0.32 g).

Workup

  1. waitleft
  2. waitto stand for 18 hours
  3. customThe mixture was then quenched with aqueous ammonium chloride solution (50 ml)
  4. extractionextracted with diethyl ether (3×50 ml)
  5. dry with materialThe combined organic extracts were dried (MgSO4)
  6. customthe solvent removed in vacuo
  7. customto give the crude product
  8. customPurification by flash chromatography (silica)
  9. washeluting with dichloromethane

Sources & evidence

ORD record
ord-4ebdf10b71a64f53ad94600fa0e888e0
Source dataset
uspto-grants-2011_09
Patent number
US08022076B2

Reaction notes

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