Cesium fluoride → 4-Methoxy-2-(1-methyl-1H-pyrazol-4-yl)pyrimidin-5-amine

HRID 2205922노트

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HRID 2205922 반응식
Cl[C:2]1[N:7]=[C:6]([O:8][CH3:9])[C:5]([NH2:10])=[CH:4][N:3]=1.[CH3:11][N:12]1[CH:16]=[C:15](B2OC(C)(C)C(C)(C)O2)[CH:14]=[N:13]1.[F-].[Cs+]>COCCOC.CO.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:9][O:8][C:6]1[C:5]([NH2:10])=[CH:4][N:3]=[C:2]([C:15]2[CH:14]=[N:13][N:12]([CH3:11])[CH:16]=2)[N:7]=1

참가 물질

7

반응물 3

HCID 25953Cesium fluorideHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 211863562-Chloro-4-methoxypyrimidin-5-amine

생성물 1

HCID 682911184-Methoxy-2-(1-methyl-1H-pyrazol-4-yl)pyrimidin-5-amine수율 93%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 8857Ethyl Acetate용매HCID 86595564Dimethoxyethane methanol용매

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온도
150 °C

실험 절차

Tetrakis(triphenylphosphine)palladium (30 mg, 0.026 mmol) was added to a solution of 2-chloro-4-methoxypyrimidin-5-amine (41 mg, 0.257 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (107 mg, 0.514 mmol) and cesium fluoride (117 mg, 0.771 mmol) in DME/MeOH (2/1, 1.6 mL). The reaction mixture was heated under microwave irradiation at 150° C. for 10 minutes. The reaction was then diluted with EtOAc and quenched with water. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were dried (Na2SO4), filtered and concentrated under reduced pressure. The crude mixture was purified via Biotage silica gel column chromatography eluting with DCM/EtOH 99/1 to 90/10 followed by filtration through a SCX-2 column to afford the title product as a white solid (49 mg, 93%). 1H NMR (500 MHz, CDCl3): δ 3.68 (br s, 2H), 3.93 (s, 3H), 4.06 (s, 3H), 7.88 (s, 1H), 7.92 (s, 1H), 8.04 (s, 1H). LC (Method B)-MS (ESI, m/z) tR 1.33 min, 206 [M+H]+

후처리

  1. customquenched with water
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with EtOAc
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude mixture was purified via Biotage silica gel column chromatography
  8. washeluting with DCM/EtOH 99/1 to 90/10
  9. filtrationfollowed by filtration through a SCX-2 column

출처 및 근거

ORD 기록
ord-9ffd82174dc1473cae9d58f9b3f065d8
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09371319B2

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