Dimethyl Sulfoxide → 2-Methoxy-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidine-4-carbaldehyde

HRID 216169Notes

Reaction equation

HRID 216169 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH3:11][O:12][C:13]1[N:18]=[C:17]([CH2:19][OH:20])[CH:16]=[C:15]([NH:21][CH2:22][CH2:23][C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=2)[N:14]=1.C(N(CC)CC)C>C(Cl)Cl.O>[CH3:11][O:12][C:13]1[N:18]=[C:17]([CH:19]=[O:20])[CH:16]=[C:15]([NH:21][CH2:22][CH2:23][C:24]2[CH:25]=[CH:26][C:27]([O:30][CH3:31])=[CH:28][CH:29]=2)[N:14]=1

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 57636124{2-Methoxy-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidin-4-yl}-methanol2×

Product 1

HCID 576360172-Methoxy-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidine-4-carbaldehydeYield 90.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of oxalyl chloride (305 μL, 3.55 mmol) in DCM (10 mL) is chilled to −78° C. To the chilled solution is added dropwise, dimethyl sulfoxide (492 μL, 6.92 mmol). After 10 minutes of stirring a solution of {2-methoxy-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidin-4-yl}-methanol [500 mg, 1.73 mmol, Intermediate (58)] in DCM (7 mL) is added via syringe. The mixture is stirred at −78° C. for 30 minutes before adding triethylamine (1.95 mL, 13.84 mmol) via syringe. After stirring for an additional 40 minutes at −78° C. the reaction is poured into water (30 mL) and this mixture is extracted twice with 30 mL DCM. The combined extracts are dried over magnesium sulfate, filtered and concentrated by rotary evaporator. The residue is taken up in toluene and re-concentrated and dried under high vacuum to afford 2-methoxy-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidine-4-carbaldehyde [450 mg, 90.5%, Intermediate (59)].

Workup

  1. additionTo the chilled solution is added dropwise
  2. additionis added via syringe
  3. stirringAfter stirring for an additional 40 minutes at −78° C. the reaction
  4. extractionthis mixture is extracted twice with 30 mL DCM
  5. dry with materialThe combined extracts are dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated by rotary evaporator
  8. concentrationre-concentrated
  9. customdried under high vacuum

Sources & evidence

ORD record
ord-d7e88452e3ff458995842a589b09dbdb
Source dataset
uspto-grants-2012_06
Patent number
US08193183B2

Reaction notes

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