Cesium fluoride → 6-Amino-2-(4-chloro-2,3-difluorophenyl)-5-vinyl-pyrimidine-4-carboxylic acid methyl ester

HRID 506460

반응식

HRID 506460 반응식
[CH3:1][O:2][C:3]([C:5]1[C:10]([CH:11]=[CH2:12])=[C:9]([NH2:13])[N:8]=[C:7](Cl)[N:6]=1)=[O:4].[Cl:15][C:16]1[CH:21]=[CH:20][C:19](B2OC(C)(C)C(C)(C)O2)=[C:18]([F:31])[C:17]=1[F:32].[F-].[Cs+]>COCCOC.O.C(OCC)(=O)C.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>[CH3:1][O:2][C:3]([C:5]1[C:10]([CH:11]=[CH2:12])=[C:9]([NH2:13])[N:8]=[C:7]([C:19]2[CH:20]=[CH:21][C:16]([Cl:15])=[C:17]([F:32])[C:18]=2[F:31])[N:6]=1)=[O:4]

참가 물질

8

반응물 3

HCID 25953Cesium fluorideHCID 569732562-(4-Chloro-2,3-difluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 594320726-Amino-2-chloro-5-vinylpyrimidine-4-carboxylic acid methyl ester

생성물 1

HCID 594321246-Amino-2-(4-chloro-2,3-difluorophenyl)-5-vinyl-pyrimidine-4-carboxylic acid methyl ester수율 36.7%

시약·촉매·용매 4

HCID 178418476HCID 178418476, 화합물촉매HCID 962Water용매HCID 80711,2-Dimethoxyethane용매HCID 8857Ethyl Acetate용매

반응 조건

온도
100 °C

실험 절차

6-Amino-2-chloro-5-vinylpyrimidine-4-carboxylic acid methyl ester (0.6 g, 2.81 mmol), 2-(4-chloro-2,3-difluorophenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (1.0 g, 3.65 mmol), bis(triphenylphosphine)-palladium(II) dichloride (197 mg, 0.28 mmol), and cesium fluoride (0.85 g, 5.6 mmol) were combined in 10 mL of 1,2-dimethoxyethane (DME) and 10 mL of water. The reaction mixture was heated in a CEM microwave reactor at 100° C. for 15 min (other temperature/time pairs used in the subsequent examples were 110° C. for 15 min; 150° C. for 5 min). The cooled reaction mixture was diluted with ethyl acetate, washed with water, dried and concentrated. The product was purified by flash chromatography on silica gel (ethyl acetate/hexane gradient) to yield the title compound (0.336 g, 36.7% yield) as a yellow solid (mp 130-132° C.); 1H NMR (CDCl3) δ 7.74 (m, 1H), 7.22 (m, 1H), 6.8 (dd, 1H), 5.62-5.7 (m, 2H), 5.67 (m, 1H), 5.42 (br s, 2H), 3.94 (s, 3H).

후처리

  1. wait150° C. for 5 min)
  2. customThe cooled reaction mixture
  3. washwashed with water
  4. customdried
  5. concentrationconcentrated
  6. customThe product was purified by flash chromatography on silica gel (ethyl acetate/hexane gradient)

출처 및 근거

ORD 기록
ord-64a68204a34d42e2a03540d5ae78e4ea
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07786044B2

연결된 노트

불러오는 중…