Dimethylformamide → HCID 20605657, compound

HRID 481101Notes

Reaction equation

HRID 481101 reaction equation
C[N:2]([CH:4]=O)[CH3:3].P(Cl)(Cl)(Cl)=O.[CH3:11][O:12][C:13]([C:15]1[CH:19]=[CH:18][N:17](C2C=C(C#N)C=CN=2)[CH:16]=1)=[O:14].[C:28](=[O:31])(O)[O-].[Na+]>C(Cl)Cl>[CH3:11][O:12][C:13]([C:15]1[C:19]([C:3]2[C:15]([C:16]#[N:17])=[CH:19][CH:18]=[CH:4][N:2]=2)=[C:18]([CH:28]=[O:31])[NH:17][CH:16]=1)=[O:14]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 69737408HCID 69737408, compound

Product 1

HCID 20605657HCID 20605657, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
10 °C

Procedure

A solution of 30 mL (360 mmol) of DMF in 200 mL of methylene chloride is cooled to 5° C. under a nitrogen atmosphere. To this is added 16 mL (180 mmol) of phosphorus oxychloride, maintaining the temperature<10° C. After addition is complete the reaction is stirred for a ½ hour. To this is added dropwise a solution of 4.0 g (18 mmol) of 4-cyano-pyridin-2-yl-1H-pyrrole-3-carboxylic acid methyl ester dissolved in 100 mL of methylene chloride. The reaction mixture is then heated to 40° C. for 48 hours. The reaction mixture is cooled to room temperature and slowly poured in 300 mL of saturated sodium bicarbonate. The organic layer is then extracted from the aqueous layer, dried (Na2SO4) and evaporated. The residue is chromatographed on 150 grams of silica gel using 1/1 ethyl acetate/hexanes as the eluant. Appropriate fractions are combined to yield 0.75 g of 4-(3-cyano-pyridin-2-yl)-5-formyl-1H-pyrrole-3-carboxylic acid methyl ester. 1H NMR (CDCl3) δ10.1 (s, 1H), 9.4 (s, 1H), 8.8 (m, 1H), 8.1 (m, 1H), 7.75 (m, 1H), 7.5 (m, 1H), 3.75 (s, 3H) Mass spectrum: m/e=256.2 (p+1). TLC (10/1 ethyl acetate/chloroform) Rf=0.7. Continued elution of the column afforded 2.5 grams of the starting pyrrole methyl ester.

Workup

  1. additionAfter addition
  2. temperatureThe reaction mixture is then heated to 40° C. for 48 hours
  3. temperatureThe reaction mixture is cooled to room temperature
  4. extractionThe organic layer is then extracted from the aqueous layer
  5. dry with materialdried (Na2SO4)
  6. customevaporated
  7. customThe residue is chromatographed on 150 grams of silica gel using 1/1 ethyl acetate/hexanes as the eluant

Sources & evidence

ORD record
ord-ed489a2136a244769e32fb1a11a6fb22
Source dataset
uspto-grants-2003_11
Patent number
US06653471B2

Reaction notes

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