Methyl iodide → 2-chloro-5-fluoro-N-methyl-N-(3-nitrophenyl)pyrimidin-4-amine

HRID 1482718Notes

Reaction equation

HRID 1482718 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([N+:15]([O-:17])=[O:16])[CH:10]=2)[C:5]([F:18])=[CH:4][N:3]=1.[C:19](=O)([O-])[O-].[Cs+].[Cs+].CI.CCCCCC.C(OCC)(=O)C>CN(C=O)C.O>[Cl:1][C:2]1[N:7]=[C:6]([N:8]([CH3:19])[C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([N+:15]([O-:17])=[O:16])[CH:10]=2)[C:5]([F:18])=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 10796Cesium carbonateHCID 21226206Ethyl acetate hexaneHCID 591746392-chloro-5-fluoro-N-(3-nitrophenyl)pyrimidin-4-amine

Product 1

HCID 867243672-chloro-5-fluoro-N-methyl-N-(3-nitrophenyl)pyrimidin-4-amineYield 86.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

In a 100 ml 3-neck RBF equipped with a magnetic stirrer, calcium chloride guard tube were charged of 2-chloro-5-fluoro-N-(3-nitrophenyl)pyrimidin-4-amine (1.10 g) in DMF (10 ml), and cesium carbonate (23.0 g), CH3I (0.641 g) was added. The reaction mixture was stirred at room temperature for 1 h. The reaction was monitored on TLC using hexane:ethyl acetate (5:5) as mobile phase. After completion, the reaction was poured into cold water. Solid precipitate was filtered out and washed with water. Solid material was dried under reduced pressure at 45° C. for 1 hr to give 1.00 g of 2-chloro-5-fluoro-N-methyl-N-(3-nitrophenyl)pyrimidin-4-amine, which was used in the next step without further purification. M+1=282.8. 1H NMR (DMSO-d6, 400 MHz) 3.50 (s, 3H), 7.701-7.741 (t, 1H, J=8), 7.883-7.902 (d, 1H, J=7.6), 8.287-8.300 (d, 1H, J=5.2), 8.325 (s, 1H).

Workup

  1. customIn a 100 ml 3-neck RBF equipped with a magnetic stirrer, calcium chloride guard tube
  2. additionwas added
  3. filtrationSolid precipitate was filtered out
  4. washwashed with water
  5. customSolid material was dried under reduced pressure at 45° C. for 1 hr

Sources & evidence

ORD record
ord-839381cbfa8b495a895b63d4a8e06075
Source dataset
uspto-grants-2016_08
Patent number
US09415049B2

Reaction notes

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