Cesium fluoride → 6-Amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-methoxypyrimidine-4-carboxylic acid methyl ester

HRID 1912301노트

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HRID 1912301 반응식
[CH3:1][O:2][C:3]([C:5]1[C:10]([O:11][CH3:12])=[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](B(O)O)=[C:18]([F:25])[C:17]=1[O:26][CH3:27].[F-].[Cs+]>COCCOC.O.C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[CH3:1][O:2][C:3]([C:5]1[C:10]([O:11][CH3:12])=[C:9]([NH2:13])[N:8]=[C:7]([C:19]2[CH:20]=[CH:21][C:16]([Cl:15])=[C:17]([O:26][CH3:27])[C:18]=2[F:25])[N:6]=1)=[O:4]

참가 물질

8

반응물 3

HCID 25953Cesium fluorideHCID 441297064-Chloro-2-fluoro-3-methoxyphenylboronic acidHCID 52270701Methyl 6-amino-2-chloro-5-methoxypyrimidine-4-carboxylate

생성물 1

HCID 591269286-Amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-methoxypyrimidine-4-carboxylic acid methyl ester수율 52.7%

시약·촉매·용매 4

HCID 6102075Dichlorobis(triphenylphosphine)palladium촉매HCID 962Water용매HCID 80711,2-Dimethoxyethane용매HCID 8857Ethyl Acetate용매

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온도
100 °C

실험 절차

6-Amino-2-chloro-5-methoxypyrimidine-4-carboxylic acid methyl ester (0.2 g, 0.9 mmol), 4-chloro-2-fluoro-3-methoxyphenylboronic acid (0.29 g, 1.4 mmol), bis(triphenylphosphine)palladium(II)dichloride (65 mg, 0.1 mmol), and cesium fluoride (0.28 g, 1.9 mmol) were combined in 1 mL of 1,2-dimethoxyethane and 1 mL of water. The reaction mixture was heated in a CEM microwave at 100° C. for 15 min (other temperature/time pairs used in the subsequent examples were 110° C. for 15 min and 150° C. for 5 min). The cooled reaction mixture was diluted with ethyl acetate, washed with water, washed with brine, dried and concentrated. The product was purified by flash chromatography on silica gel (hexane/ethyl acetate gradient) to yield the title compound (162 mg, 51.1% yield): mp 155-158° C.; 1H NMR (CDCl3): δ 7.58 (dd, 1H), 7.20 (dd, 1H), 5.56 (br s, 2H) 4.00 (s, 3H), 3.99 (d, 3H), 3.94 (s, 3H).

후처리

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

출처 및 근거

ORD 기록
ord-6d2460477e04453ab6d3a848a2ef9ddd
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08609592B2

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