Methylamine → 2,4-Dichloro-N-methyl-5-pyrimidinecarboxamide

HRID 2284902Notes

Reaction equation

HRID 2284902 reaction equation
[CH3:1][NH2:2].C1COCC1.[Cl:8][C:9]1[N:14]=[C:13]([Cl:15])[C:12]([C:16](Cl)=[O:17])=[CH:11][N:10]=1.C(OCC)(=O)C>C(Cl)Cl.CCCCCC>[Cl:8][C:9]1[N:14]=[C:13]([Cl:15])[C:12]([C:16]([NH:2][CH3:1])=[O:17])=[CH:11][N:10]=1

Participants

7

Reactant 4

HCID 6329MethylamineHCID 8028TetrahydrofuranHCID 8857Ethyl AcetateHCID 137841122,4-Dichloropyrimidine-5-carbonyl chloride

Product 1

HCID 578270102,4-Dichloro-N-methyl-5-pyrimidinecarboxamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8058HexaneSolvent

Procedure

To a solution of methyl amine (2M) in THF (2.4 mL, 4.70 mmol) in DCM (50 ml), TEA (963 mg, 9.50 mmol) and 2,4-dichloropyrimidine-5-carbonyl chloride (1 g, 4.70 mmol) were added slowly at −78° C. for 1 h. TLC showed completion of starting material (TLC system: 10% ethyl acetate in hexane (Rf): 0.3). The reaction mixture was diluted with DCM (50 ml), washed with water (2×30 ml) and a saturated solution of NaHCO3. The organic layer was separated, dried over sodium sulphate, and concentrated. Crude compound was purified by column chromatography using silica gel (100-200 mesh) with 5% ethyl acetate in hexane to obtain 2,4-dichloro-N-methylpyrimidine-5-carboxamide as white solid. Yield: (400 mg, 33%). 1HNMR (400 MHz, CDCl3) δ 8.98 (s, 1H), 6.50 (br s, 1H), 3.07 (d, 3H, J=4.8 Hz).

Workup

  1. washwashed with water (2×30 ml)
  2. customThe organic layer was separated
  3. dry with materialdried over sodium sulphate
  4. concentrationconcentrated
  5. customCrude compound was purified by column chromatography

Sources & evidence

ORD record
ord-f2cc19585cc3408c960f4d0e2810f7d9
Source dataset
uspto-grants-2015_09
Patent number
US09145387B2

Reaction notes

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