Water → 2,4-Dichloro-6-(4-methylpent-3-en-1-yl)pyrimidine

HRID 23193

反応式

HRID 23193 の反応式
[Li+].CC([N-]C(C)C)C.[Cl:9][C:10]1[N:15]=[C:14]([Cl:16])[CH:13]=[C:12]([CH3:17])[N:11]=1.[CH3:18][C:19]([CH3:23])=[CH:20][CH2:21]Br.O>C1COCC1.C(OCC)(=O)C>[Cl:9][C:10]1[N:15]=[C:14]([Cl:16])[CH:13]=[C:12]([CH2:17][CH2:21][CH:20]=[C:19]([CH3:23])[CH3:18])[N:11]=1

参加物

7

反応物 4

HCID 962WaterHCID 700922-Butene, 1-bromo-3-methyl-HCID 794712,4-Dichloro-6-methylpyrimidineHCID 2724682Lithium diisopropylamide

生成物 1

HCID 224884832,4-Dichloro-6-(4-methylpent-3-en-1-yl)pyrimidine収率 74.3%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒3 回HCID 8857Ethyl Acetate溶媒

実験手順

The above synthesis may be carried out as follows: To a solution of LDA (1.28 g, 12 mmol) in THF (30 mL) at −78° C. was added 2,4-dichloro-6-methylpyrimidine (1.96 g, 12 mmol) in THF (15 mL). After stirring for 15 minutes, 3,3-dimethylallyl bromide (1.79 g, 12 mmol) in THF (5 mL) was added dropwise. After the reaction warmed to ambient temperature, water and ethyl acetate was added. The organic layer was separated, the solvent was removed in vacuo, and the residue was chromatographed (ethyl acetate/hexane, 1/19) to give 2.06 g (74%) of 2,4-dichloro-6-(4-methyl-3-pentenyl)pyrimidine (1H NMR (CDCl3) δ 7.15 (s, 1), 5.10 (t, 1), 2.80 (t, 2), 2.45 (m, 2), 1.70 (s, 3), 1.55 (s, 3). To a solution of NaIO4 (17 g, 81 mmol) and KMnO4 (251 mg, 1.59 mmol) in water was added K2CO3 (1.29 g, 9.38 mmol) and 2,4-dichloro-6-(4-methyl-3-pentenyl)pyrimidine (2.06 g, 8.9 mmol) in t-butanol. After stirring for 16 hours, the reaction was acidified to pH 3 and extracted with ethyl acetate. The organic layer was extracted with aqueous NaHCO3. The aqueous layer was acidified to pH 3 and extracted with ethyl acetate. The organic layer was dried and the solvent removed in vacuo to give 980 mg of 3-(2,4-dichloropyrimidin-6-yl)propionic acid (the compound of formula (XIX)), 1H NMR (CDCl3) δ 7.30 (s, 1), 3.05 (t, 2), 2.90 (t, 2). The acid was coupled to piperonylamine under standard conditions with isobutyl chloroformate and N-methylmorpholine to give the compound of formula (XX). Imidazole was added under standard conditions (1-trimethylsilylimidazole and CsF in DMF at 60° C.) to give N-[(1,3-benzodioxol-5-yl)ethyl]-6-chloro-2-(1H-imidazol-1-yl)pyrimidine-4-propionamide (the compound of formula (Ihh)); MS: 386 (M+H)+.

後処理

  1. customThe above synthesis
  2. customThe organic layer was separated
  3. customthe solvent was removed in vacuo
  4. customthe residue was chromatographed (ethyl acetate/hexane, 1/19)

出典と根拠

ORDレコード
ord-e715b78e65274f56960fec0e258a3390
出典データセット
uspto-grants-2005_02
特許番号
US06849739B2

関連ノート

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