Potassium Carbonate → 4-(2-Amino-6-chloropyrimidin-4-yl)-N-(tert-butoxycarbonyl)-L-phenylalanine

HRID 2098439ノート

反応式

HRID 2098439 の反応式
[NH2:1][C:2]1[N:7]=[C:6]([Cl:8])[CH:5]=[C:4](Cl)[N:3]=1.B([O-])[O-].[C:13]([O:17][C:18]([NH:20][C@@H:21]([CH2:25][C:26]1[CH:31]=[CH:30][C:29](B2OC(C)(C)C(C)(C)O2)=[CH:28][CH:27]=1)[C:22]([OH:24])=[O:23])=[O:19])([CH3:16])([CH3:15])[CH3:14].C(=O)([O-])[O-].[K+].[K+]>O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(O)C.O>[NH2:1][C:2]1[N:3]=[C:4]([C:29]2[CH:28]=[CH:27][C:26]([CH2:25][C@H:21]([NH:20][C:18]([O:17][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:19])[C:22]([OH:24])=[O:23])=[CH:31][CH:30]=2)[CH:5]=[C:6]([Cl:8])[N:7]=1

参加物

8

反応物 4

HCID 11430Potassium CarbonateHCID 655222-Amino-4,6-dichloropyrimidineHCID 10644158(S)-2-(Tert-butoxycarbonylamino)-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)phenyl]propanoic acidHCID 178514824HCID 178514824、化合物

生成物 1

HCID 251913394-(2-Amino-6-chloropyrimidin-4-yl)-N-(tert-butoxycarbonyl)-L-phenylalanine収率 79.3%

試薬・触媒・溶媒 3

HCID 178418476HCID 178418476、化合物触媒HCID 962Water溶媒HCID 19096565Water ethanol溶媒

反応条件

温度
80 °C

実験手順

To a 500 ml 3-neck round-bottom flask equipped with a mechanical stirrer, a thermocontroller was charged 2-amino-4,6-dichloropyrimidine (12.57 g, 1.5 equiv), boronate compound 7 (20.00 g, 51.1 mmol), potassium carbonate (21.19 g, 3.0 equiv) and ethanol/water (200 ml, 5:1 by volume). The mixture was stirred and the catalyst bis(triphenylphosphine)palladium(II) dichloride (359 mg, 1 mol %) was added. The mixture was heated to 80° C. and stirred for 2 hours. The reaction was cooled to room temperature and diluted with water (100 ml). The mixture was then concentrated under reduced pressure to remove most of ethanol and 1 N NaOH (60 ml) was added. The mixture was extracted twice with ethyl acetate (2×200 ml) and the aqueous layer was acidified to pH˜3 using 1 N HCl. The mixture was extracted with ethyl acetate twice (200 ml and 100 ml, respectively) and the combined organic layers were concentrated and the residue was purified by column chromatography (gradient 1:20 to 1:10 methanol/dichloromethane) to afford compound 8 as a pale yellow solid (15.92 g, 79%).

後処理

  1. customTo a 500 ml 3-neck round-bottom flask equipped with a mechanical stirrer
  2. stirringstirred for 2 hours
  3. temperatureThe reaction was cooled to room temperature
  4. concentrationThe mixture was then concentrated under reduced pressure
  5. customto remove most of ethanol and 1 N NaOH (60 ml)
  6. additionwas added
  7. extractionThe mixture was extracted twice with ethyl acetate (2×200 ml)
  8. extractionThe mixture was extracted with ethyl acetate twice (200 ml and 100 ml
  9. concentrationrespectively) and the combined organic layers were concentrated
  10. customthe residue was purified by column chromatography (gradient 1:20 to 1:10 methanol/dichloromethane)

出典と根拠

ORDレコード
ord-09dd041af7b245acb300f6e39e1398cf
出典データセット
uspto-grants-2013_05
特許番号
US08450532B2

反応ノート

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