N-Phenylglycine ethyl ester → HCID 24937863, compound

HRID 2428050Notes

Reaction equation

HRID 2428050 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]([O:10]CC)=O)[C:5]([N+:13]([O-])=O)=[C:4]([N:16]([CH2:23][C:24]([O:26]CC)=O)[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:3]=1.Cl[C:30]1N=[C:34]([C:36](OCC)=O)[C:33]([N+]([O-])=O)=[C:32](Cl)[N:31]=1.C1([NH:51]CC(OCC)=O)C=CC=CC=1.C(N(C(C)C)CC)(C)C.C(=O)(O)[O-].[Na+]>O1CCCC1>[O:26]=[C:24]1[CH2:23][N:16]([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:4]2[N:3]=[C:2]([C:34]3[CH:36]=[CH:30][N:31]=[CH:32][CH:33]=3)[N:7]=[C:6]([C:8]([NH2:51])=[O:10])[C:5]=2[NH:13]1

Participants

7

Reactant 5

HCID 75190N-Phenylglycine ethyl esterHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 2761044Ethyl 2,6-dichloro-5-nitropyrimidine-4-carboxylateHCID 57474561HCID 57474561, compound

Product 1

HCID 24937863HCID 24937863, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Ethyl 2-chloro-6-((2-ethoxy-2-oxoethyl)(phenyl)amino)-5-nitropyrimidine-4-carboxylate. A solution of ethyl 2,6-dichloro-5-nitropyrimidine-4-carboxylate (1.5 g, 5.67 mmol) in anhydrous tetrahydrofuran (20 mL) was chilled to −78° C. under nitrogen. A solution of ethyl 2-(phenylamino)acetate (1.1 g, 6.22 mmol) and diisopropylethylamine (3.0 mL, 17.01 mmol) in anhydrous tetrahydrofuran (10 mL) was then added dropwise, with stirring, over 10 min. The reaction was stirred at −78° C. for 6 h, followed by addition of aqueous sodium bicarbonate solution (saturated, 10 mL). The mixture was extracted with ethyl acetate (3×10 mL). The organic phase was dried over sodium sulfate and concentrated to a residue which was purified by chromatography on a normal phase silica gel column (0-10% ethyl acetate in hexanes). Fractions containing product were combined and the solvent evaporated to provide the title compound (1.1 g, 2.89 mmol, 41% yield). MS (ESI) m/z 409.5 [M+1]+.

Workup

  1. stirringThe reaction was stirred at −78° C. for 6 h
  2. extractionThe mixture was extracted with ethyl acetate (3×10 mL)
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. concentrationconcentrated to a residue which
  5. customwas purified by chromatography on a normal phase silica gel column (0-10% ethyl acetate in hexanes)
  6. additionFractions containing product
  7. customthe solvent evaporated

Sources & evidence

ORD record
ord-20625c57f952453dacef2475dcfb7efe
Source dataset
uspto-grants-2011_06
Patent number
US07968556B2

Reaction notes

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