Water → 3,3-Dimethyl-6-(2-methyl-4-(4-(tetrahydro-2H-pyran-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-4-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

HRID 1047216노트

반응식

HRID 1047216 반응식
[CH3:1][C:2]1[CH:3]=[C:4]([C:17]2[N:21]([CH:22]3[CH2:27][CH2:26][CH2:25][CH2:24][O:23]3)[CH:20]=[N:19][N:18]=2)[CH:5]=[CH:6][C:7]=1B1OC(C)(C)C(C)(C)O1.Br[C:29]1[N:30]=[C:31]2[N:38]([CH2:39][CH2:40][CH:41]3[CH2:46][CH2:45][O:44][CH2:43][CH2:42]3)[C:37]([CH3:48])([CH3:47])[C:36](=[O:49])[NH:35][C:32]2=[N:33][CH:34]=1.ClCCl.C(=O)([O-])[O-].[Na+].[Na+].O>O1CCOCC1.C(O)(C)C.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]>[CH3:47][C:37]1([CH3:48])[C:36](=[O:49])[NH:35][C:32]2=[N:33][CH:34]=[C:29]([C:7]3[CH:6]=[CH:5][C:4]([C:17]4[N:21]([CH:22]5[CH2:27][CH2:26][CH2:25][CH2:24][O:23]5)[CH:20]=[N:19][N:18]=4)=[CH:3][C:2]=3[CH3:1])[N:30]=[C:31]2[N:38]1[CH2:39][CH2:40][CH:41]1[CH2:46][CH2:45][O:44][CH2:43][CH2:42]1

참가 물질

9

반응물 5

HCID 962WaterHCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 533752276-bromo-3,3-dimethyl-4-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-oneHCID 533752283-(3-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4-(tetrahydro-2H-pyran-2-yl)-4H-1,2,4-triazole

생성물 1

HCID 533752293,3-Dimethyl-6-(2-methyl-4-(4-(tetrahydro-2H-pyran-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-4-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one수율 97%

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 3776Isopropanol용매HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

3-(3-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4-(tetrahydro-2H-pyran-2-yl)-4H-1,2,4-triazole (1 equiv), 6-bromo-3,3-dimethyl-4-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one (1 equiv), [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (0.1 equiv), 1 M sodium carbonate in water (3 equiv), 1,4-dioxane and isopropanol were combined and the system was purged with nitrogen. The resulting mixture was stirred vigorously and heated at 100° C. for 1.5 h. The resulting mixture was cooled to room temperature, diluted with methanol and the volatiles removed under reduced pressure. The residue was partitioned between dichloromethane and water, shaken and the layers separated. The water layer was extracted with dichloromethane. The combined organics were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified using flash chromatography (20-100% ethyl acetate in hexane followed by 0-10% methanol in dichloromethane) to give the desired product in 97% yield. MS (ESI) m/z 532.7 [M+1]+.

후처리

  1. customthe system was purged with nitrogen
  2. temperatureThe resulting mixture was cooled to room temperature
  3. additiondiluted with methanol
  4. customthe volatiles removed under reduced pressure
  5. customThe residue was partitioned between dichloromethane and water
  6. stirringshaken
  7. customthe layers separated
  8. extractionThe water layer was extracted with dichloromethane
  9. dry with materialThe combined organics were dried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified

출처 및 근거

ORD 기록
ord-2408f9ff83ca47939b3366c50fca734a
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08569494B2

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