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Toluene → N2-((1S)-1-(4-Fluorophenyl)ethyl)-4-(1-methyl-1H-pyrazol-4-yl)-N6-2-pyrazinyl-2,6-pyridinediamine

HRID 2043416
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HRID 2043416 반응식
Cl[C:2]1[N:7]=[C:6]([NH:8][C@H:9]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)[CH3:10])[CH:5]=[C:4]([C:18]2[CH:19]=[N:20][N:21]([CH3:23])[CH:22]=2)[CH:3]=1.[NH2:24][C:25]1[CH:30]=[N:29][CH:28]=[CH:27][N:26]=1.CC(C)([O-])C.[Na+].C1(C)C=CC=CC=1>C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>[F:17][C:14]1[CH:15]=[CH:16][C:11]([C@@H:9]([NH:8][C:6]2[CH:5]=[C:4]([C:18]3[CH:19]=[N:20][N:21]([CH3:23])[CH:22]=3)[CH:3]=[C:2]([NH:24][C:25]3[CH:30]=[N:29][CH:28]=[CH:27][N:26]=3)[N:7]=2)[CH3:10])=[CH:12][CH:13]=1
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참가 물질

8

반응물 4

HCID 1140TolueneHCID 78747AminopyrazineHCID 23676156Sodium t-butoxideHCID 86659376HCID 86659376, 화합물

생성물 1

HCID 46866319N2-((1S)-1-(4-Fluorophenyl)ethyl)-4-(1-methyl-1H-pyrazol-4-yl)-N6-2-pyrazinyl-2,6-pyridinediamine수율 79.9%

시약·촉매·용매 3

HCID 9811564
Bis(dibenzylideneacetone)palladium
촉매
HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl촉매
HCID 8857Ethyl Acetate용매

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온도
100 °C

실험 절차

1.34 g of (S)-6-chloro-N-[1-(4-fluorophenyl)ethyl]-4-(1-methyl-1H-pyrazol-4-yl)pyridine-2-amine synthesized by the same method as in Steps 1 and 2 of Example 4, 423 mg of 2-aminopyrazine, 154 mg of 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl, 544 mg of sodium t-butoxide and 74 mg of tris(dibenzylideneacetone)dipalladium were added in turn to 13 ml of degassed toluene, and the mixture was stirred at 100° C. for 1 hour under argon atmosphere. The reaction solution was diluted with ethyl acetate. The solution was washed with water and then dried over magnesium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography to obtain 1.26 g of (S)—N2-[1-(4-fluorophenyl)ethyl]-4-(1-methyl-1H-pyrazol-4-yl)-N6-(pyrazin-2-yl)pyridine-2,6-diamine as pale yellow powder. Subsequently, 1.0 g of the obtained (S)—N2-[1-(4-fluorophenyl)ethyl]-4-(1-methyl-1H-pyrazol-4-yl)-N6-(pyrazin-2-yl)pyridine-2,6-diamine was dissolved in 1 ml of methanol, and 300 mg of maleic acid was added. The reaction solution was added with 6 ml of ethyl acetate, and stirred at room temperature for 2 hours. The precipitated solid was filtered to obtain 1.1 g of the objective compound as white powder.

후처리

  1. washThe solution was washed with water
  2. dry with materialdried over magnesium sulfate
  3. distillationThe solvent was distilled off under reduced pressure
  4. customthe obtained residue was purified by silica gel column chromatography

출처 및 근거

ORD 기록
ord-688686ce85814320bc0738d1e5694a9e
출처 데이터셋
uspto-grants-2013_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08586591B2

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