Methyl iodide → Methyl 2,4-dichloro-6-(m-tolylamino)pyrimidine-5-carboxylate

HRID 515965Notes

Reaction equation

HRID 515965 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([C:9]([OH:11])=[O:10])=[C:4]([NH:12][C:13]2[CH:14]=[C:15]([CH3:19])[CH:16]=[CH:17][CH:18]=2)[N:3]=1.[C:20]([O-])(O)=O.[Na+].IC>CN(C=O)C>[Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([C:9]([O:11][CH3:20])=[O:10])=[C:4]([NH:12][C:13]2[CH:14]=[C:15]([CH3:19])[CH:16]=[CH:17][CH:18]=2)[N:3]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 516892Sodium Bicarbonate2×HCID 583175932,4-Dichloro-6-(m-tolylamino)pyrimidine-5-carboxylic acid

Product 1

HCID 58317610Methyl 2,4-dichloro-6-(m-tolylamino)pyrimidine-5-carboxylateYield 65.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2,4-dichloro-6-(m-tolylamino)pyrimidine-5-carboxylic acid (7.67 g, 25.7 mmol) in DMF (80 mL) was added NaHCO3 (3.30 g, 39.3 mmol) and iodomethane (1.605 mL, 25.7 mmol) at 0° C. The mixture was stirred at RT for 14 h, after which saturated aq NaHCO3 was added. The mixture was extracted with EtOAc. The organic layers were washed with aqueous NaHOC3, water, and brine, were dried over anhydrous Na2SO4, and then filtered through SiO2. The filtrate was concentrated under reduced pressure. The residue was triturated with isopropyl ether and filtered to give a first batch (5.28 g) of the title compound. The filtrate was concentrated, triturated with IPE, and filtered to give a second batch (0.66 g) of the title compound as a yellow solid (total 5.94 g, 74%). 1H NMR (500 MHz, CDCl3) δ ppm 2.38 (s, 3H), 4.00 (s, 3H), 7.02-7.03 (m, 1H), 7.27-7.33 (m, 2H), 7.44-7.46 (m, 1H), 10.30 (br s, 1H). [M+H] calc'd for C13H12Cl2N3O2, 312; found, 312.

Workup

  1. extractionThe mixture was extracted with EtOAc
  2. washThe organic layers were washed with aqueous NaHOC3, water, and brine
  3. dry with materialwere dried over anhydrous Na2SO4
  4. filtrationfiltered through SiO2
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customThe residue was triturated with isopropyl ether
  7. filtrationfiltered

Sources & evidence

ORD record
ord-323c8268f7ba4547854565f2b9a26b7e
Source dataset
uspto-grants-2015_08
Patent number
US09108970B2

Reaction notes

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