Pyridine → 5-tert-Butyl-3-(3-p-tolyl-ureido)-1H-pyrrole-2-carboxylic acid methyl ester

HRID 1698913Notes

Reaction equation

HRID 1698913 reaction equation
[NH2:1][C:2]1[CH:6]=[C:5]([C:7]([CH3:10])([CH3:9])[CH3:8])[NH:4][C:3]=1[C:11]([O:13][CH3:14])=[O:12].N1C=CC=CC=1.[C:21](Cl)(Cl)=[O:22].[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][CH:27]=1>C1(C)C=CC=CC=1>[C:11]([C:3]1[NH:4][C:5]([C:7]([CH3:10])([CH3:8])[CH3:9])=[CH:6][C:2]=1[NH:1][C:21]([NH:25][C:26]1[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][CH:27]=1)=[O:22])([O:13][CH3:14])=[O:12]

Participants

6

Reactant 4

HCID 1049PyridineHCID 6371PhosgeneHCID 7813p-ToluidineHCID 18322367methyl 3-amino-5-(tert-butyl)-1H-pyrrole-2-carboxylate

Product 1

HCID 98839395-tert-Butyl-3-(3-p-tolyl-ureido)-1H-pyrrole-2-carboxylic acid methyl esterYield 80%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of methyl 3-amino-5-tert-butylpyrrole-2-carboxylate (12 mg, 0.062 mmol) and anh. pyridine (0.25 mL, 3.06 mmol, 49.4 equiv) in anh. toluene (1 mL) was rapidly added phosgene (1.93M in toluene, 0.32 mL, 0.62 mmol, 10 equiv). After 30 min, the orange suspension was concentrated under reduced pressure, then successively charged with anh. toluene (1 mL) and concentrated (2×). Finally, toluene (2 mL) was added followed by p-toluidine (10 mg, 0.094 mmol). The mixture was heated at 90° C. for 3 h, then was concentrated under reduced pressure. The residue was purified by preparative TLC (2 plates, 20×20 cm×0.25 mm, 2% MeOH/CH2Cl2). The major UV-active band was isolated and the product was extracted from the silica using 5% MeOH/CH2Cl2 to give N-(2-carbomethoxy-5-tert-butyl-3-pyrrolyl)-N′-(4-methylphenyl)urea as a pale yellow amorphous solid (0.016 g, 80%): 1H NMR (d6-DMSO ) δ1.23 (s, 9H), 2.20 (s, 3H), 3.78 (s, 3H), 6.54 (d, J=3.0 Hz, 1H), 7.04 (d, J=8.5 Hz, 2H), 7.32 (d, J=8.5 Hz, 2H), 8.61 (s, 1H), 9.51 (s, 1H), 10.85 (br d, J=2.2 Hz, 1H); 13C NMR (MeOD, CDCl3, partial spectrum) δ19.7, 29.0 (3C), 31.5, 50.0, 97.4, 105.9, 119.6 (2C), 128.9 (2C), 132.2, 136.2, 147.6, 153.5, 161.9; FTIR (KBr) 3341 (s), 2947 (m), 1676 (s), 1583 (s), 1548 (s), 1456 (s), 1279 (s), 1208 (s), 1094 (s); cm−1; FAB-LRMS m/z (rel abundance) 330 (M+H, 47%).

Workup

  1. concentrationthe orange suspension was concentrated under reduced pressure
  2. additionsuccessively charged with anh. toluene (1 mL)
  3. concentrationconcentrated (2×)
  4. additionFinally, toluene (2 mL) was added
  5. concentrationwas concentrated under reduced pressure
  6. customThe residue was purified by preparative TLC (2 plates, 20×20 cm×0.25 mm, 2% MeOH/CH2Cl2)
  7. customThe major UV-active band was isolated
  8. extractionthe product was extracted from the silica using 5% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-8f6f18dd68cf4535986f2d10368c5c49
Source dataset
uspto-grants-2002_02
Patent number
US06344476B1

Reaction notes

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