1-Methylimidazole → Diethyl 2-chloro-4-(4-chloro-5-(trifluoromethyl)pyrimidin-2-ylamino)-3-methoxybenzylphosphonate

HRID 2279863Notes

Reaction equation

HRID 2279863 reaction equation
Cl[C:2]1[N:7]=[C:6]([Cl:8])[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=1.[NH2:13][C:14]1[CH:28]=[CH:27][C:17]([CH2:18][P:19](=[O:26])([O:23][CH2:24][CH3:25])[O:20][CH2:21][CH3:22])=[C:16]([Cl:29])[C:15]=1[O:30][CH3:31].CN1C=CN=C1>[Cl-].[Cl-].[Zn+2].C(O)(C)(C)C.ClCCCl>[Cl:29][C:16]1[C:15]([O:30][CH3:31])=[C:14]([NH:13][C:2]2[N:7]=[C:6]([Cl:8])[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=2)[CH:28]=[CH:27][C:17]=1[CH2:18][P:19](=[O:26])([O:23][CH2:24][CH3:25])[O:20][CH2:21][CH3:22]

Participants

7

Reactant 3

HCID 13901-MethylimidazoleHCID 27827742,4-Dichloro-5-(trifluoromethyl)pyrimidineHCID 86697801Diethyl 4-amino-2-chloro-3-methoxybenzylphosphonate

Product 1

HCID 86697800Diethyl 2-chloro-4-(4-chloro-5-(trifluoromethyl)pyrimidin-2-ylamino)-3-methoxybenzylphosphonate

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 111,2-DichloroethaneSolvent2×HCID 6386tert-ButanolSolvent2×

Procedure

To a solution of 2,4-dichloro-5-trifluoromethylpyrimidine (2.1 g, 9.77 mmol) in a 1:1 mixture of DCE and t-butanol (20 mL) was added ZnCl2 (1M, 10 mL) and stirred for half an hour at RT. After cooling at 0° C. diethyl 4-amino-2-chloro-3-methoxybenzylphosphonate (3 g, 9.77 mmol) in a 1:1 mixture of DCE and t-butanol (20 mL) was added followed by N-methylimidazole (800 mg, 9.75 mmol) drop wise while stirring was continued for 24 hrs. The solvents were removed under reduced pressure and the residue was purified by column chromatography (SiO2, ethyl acetate and hexanes (1:1)) to yield the desired compound in 1.5 g (32%) yield. 1H NMR (300 MHz, CDCl3) δ 8.61 (s, 1H), 8.38 (d, 1H), 8.03 (s, 1H), 4.01-4.18 (q, 4H), 3.98 (s, 3H), 3.29 (d, 2H), 1.24 (t, 6H).

Workup

  1. additionwas added
  2. stirringwhile stirring
  3. customThe solvents were removed under reduced pressure
  4. customthe residue was purified by column chromatography (SiO2, ethyl acetate and hexanes (1:1))

Sources & evidence

ORD record
ord-f3ec5260c4db47e691feb64b374fb3d5
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Reaction notes

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