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

HRID 2279863노트

반응식

HRID 2279863 반응식
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]

참가 물질

7

반응물 3

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

생성물 1

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

시약·촉매·용매 3

HCID 3007855Zincchloride촉매HCID 111,2-Dichloroethane용매2회HCID 6386tert-Butanol용매2회

실험 절차

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).

후처리

  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))

출처 및 근거

ORD 기록
ord-f3ec5260c4db47e691feb64b374fb3d5
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09133224B2

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