Potassium Carbonate → 1H-1,2,3-Triazolo[4,5-b]pyrazine, 1-[[(2S)-4-[5-[4-[(4-methyl-1-piperazinyl)methyl]phenyl]-2-pyrimidinyl]-2-morpholinyl]methyl]-6-(1-methyl-1H-pyrazol-4-yl)-

HRID 1478608노트

반응식

HRID 1478608 반응식
Br[C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12]C[C@H:10]([CH2:14][N:15]3[C:19]4=[N:20][C:21]([C:24]5[CH:25]=[N:26][N:27]([CH3:29])[CH:28]=5)=[CH:22][N:23]=[C:18]4[N:17]=[N:16]3)[CH2:9]2)=[N:6][CH:7]=1.[CH3:30][N:31]1[CH2:36][CH2:35][N:34]([CH2:37][C:38]2[CH:43]=[CH:42][C:41](B3OC(C)(C)C(C)(C)O3)=[CH:40][CH:39]=2)[CH2:33][CH2:32]1.C([O-])([O-])=[O:54].[K+].[K+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:29][N:27]1[CH:28]=[C:24]([C:21]2[N:20]=[C:19]3[N:15]([CH2:14][C@H:10]4[O:54][CH2:12][CH2:13][N:8]([C:5]5[N:4]=[CH:3][C:2]([C:41]6[CH:40]=[CH:39][C:38]([CH2:37][N:34]7[CH2:33][CH2:32][N:31]([CH3:30])[CH2:36][CH2:35]7)=[CH:43][CH:42]=6)=[CH:7][N:6]=5)[CH2:9]4)[N:16]=[N:17][C:18]3=[N:23][CH:22]=2)[CH:25]=[N:26]1

참가 물질

7

반응물 3

HCID 11430Potassium CarbonateHCID 467390391-Methyl-4-{[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methyl}piperazineHCID 118364803HCID 118364803, 화합물

생성물 1

HCID 735047191H-1,2,3-Triazolo[4,5-b]pyrazine, 1-[[(2S)-4-[5-[4-[(4-methyl-1-piperazinyl)methyl]phenyl]-2-pyrimidinyl]-2-morpholinyl]methyl]-6-(1-methyl-1H-pyrazol-4-yl)-수율 71%

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 312751,4-Dioxane용매

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온도
80 °C

실험 절차

(S)-1-((1-(5-bromopyrimidin-2-yl)piperidin-3-yl)methyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazine (250 mg, 0.55 mmol), 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)benzyl)piperazine (210 mg, 0.66 mmol), Pd(dppf)2Cl2 (23 mg, 0.027 mmol), and K2CO3 (228 mg, 1.65 mmol) were dissolved in dioxane (6 ml)+H2O (1.5 ml), and then degassed with N2 (gas), followed by stirring at 80° C. for hours. After the completion of the reaction, the reaction mixture was extracted with H2O, EA, and brine, followed by drying (Na2SO4), filtration, and concentration under reduced pressure, and the residue was purified by column chromatography (MeOH:MC=1:10), to give (S)-2-((6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)-4-(5-(4-((4-methylpiperazin-1-yl)methyl)phenyl)pyrimidin-2-yl)morpholine (210 mg, 71%).

후처리

  1. customdegassed with N2 (gas)
  2. customAfter the completion of the reaction
  3. extractionthe reaction mixture was extracted with H2O, EA, and brine
  4. customby drying
  5. filtration(Na2SO4), filtration, and concentration under reduced pressure
  6. customthe residue was purified by column chromatography (MeOH:MC=1:10)

출처 및 근거

ORD 기록
ord-12873f22ccd64361b1fa3097a4c117c3
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09403831B2

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