N-(2-Fluoro-4-iodo-phenyl)-2-pyrimidin-4-ylmethyl-malonamic acid ethyl ester → 7-(2-Fluoro-4-iodo-phenylamino)-pyrrolo[1,2-c]pyrimidine-6-carboxylic acid ethyl ester

HRID 450115Notes

Reaction equation

HRID 450115 reaction equation
[CH2:1]([O:3][C:4](=[O:24])[CH:5]([CH2:17][C:18]1[CH:23]=[CH:22][N:21]=[CH:20][N:19]=1)[C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([I:15])=[CH:11][C:10]=1[F:16])=O)[CH3:2].O(Cl)Cl.[P+5]>C1(C)C=CC=CC=1>[CH2:1]([O:3][C:4]([C:5]1[CH:17]=[C:18]2[CH:23]=[CH:22][N:21]=[CH:20][N:19]2[C:6]=1[NH:8][C:9]1[CH:14]=[CH:13][C:12]([I:15])=[CH:11][C:10]=1[F:16])=[O:24])[CH3:2]

Participants

4

Reactant 2

HCID 67234244N-(2-Fluoro-4-iodo-phenyl)-2-pyrimidin-4-ylmethyl-malonamic acid ethyl esterHCID 178479711HCID 178479711, compound

Product 1

HCID 672343197-(2-Fluoro-4-iodo-phenylamino)-pyrrolo[1,2-c]pyrimidine-6-carboxylic acid ethyl esterYield 16.4%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of N-(2-fluoro-4-iodo-phenyl)-2-pyrimidin-4-ylmethyl-malonamic acid ethyl ester (4 g, 9.02 mmol) in toluene (120 mL) was added phosphorous (V) oxychloride (4.2 mL, 45.1 mmol). The reaction was heated at reflux for 16 hours then concentrated in vacuo. The resultant residue was dissolved in ethyl acetate (30 mL), washed with saturated aqueous sodium bicarbonate solution (20 mL) and the aqueous fraction extracted twice with ethyl acetate (2×10 mL). The combined organic fractions were washed with brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0-40% ethyl acetate in cyclohexane) to yield a dark brown solid. The solid was triturated with ether (10 mL) to yield the title compound as a light brown solid (0.63 g, 16%). LCMS (Method B): RT=3.95 min, M+H+=426.

Workup

  1. temperatureThe reaction was heated
  2. temperatureat reflux for 16 hours
  3. concentrationthen concentrated in vacuo
  4. dissolutionThe resultant residue was dissolved in ethyl acetate (30 mL)
  5. washwashed with saturated aqueous sodium bicarbonate solution (20 mL)
  6. extractionthe aqueous fraction extracted twice with ethyl acetate (2×10 mL)
  7. washThe combined organic fractions were washed with brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. customto yield a dark brown solid
  11. customThe solid was triturated with ether (10 mL)

Sources & evidence

ORD record
ord-e20f52c92f51455fbf65d32b2bbc7cb4
Source dataset
uspto-grants-2013_07
Patent number
US08486963B2

Reaction notes

Loading…