Water → HCID 178423524、化合物

HRID 454326ノート

反応式

HRID 454326 の反応式
[CH3:1][C:2]1([CH3:39])[C:29](=[O:30])[NH:28][C:5]2=[N:6][CH:7]=[C:8]([C:10]3[CH:15]=[CH:14][C:13]([C:16]4[N:20](C5CCCCO5)[CH:19]=[N:18][N:17]=4)=[CH:12][C:11]=3[CH3:27])[N:9]=[C:4]2[N:3]1[CH2:31][CH2:32][CH:33]1[CH2:38][CH2:37][O:36][CH2:35][CH2:34]1.CC1C=C(C2N(C3CCCCO3)C=NN=2)C=CC=1B1OC(C)(C)C(C)(C)O1.BrC1N=C2N(CCC3CCOCC3)C(C)(C)C(=O)NC2=NC=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]>[CH3:1][C:2]1([CH3:39])[C:29](=[O:30])[NH:28][C:5]2=[N:6][CH:7]=[C:8]([C:10]3[CH:15]=[CH:14][C:13]([C:16]4[NH:20][CH:19]=[N:18][N:17]=4)=[CH:12][C:11]=3[CH3:27])[N:9]=[C:4]2[N:3]1[CH2:31][CH2:32][CH:33]1[CH2:34][CH2:35][O:36][CH2:37][CH2:38]1

参加物

10

反応物 6

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-triazoleHCID 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)-one

生成物 1

HCID 178423524HCID 178423524、化合物収率 97%

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 3776Isopropanol溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

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. 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]+.

後処理

  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

出典と根拠

ORDレコード
ord-ccbdd2599e9c42a0a186f264e1417820
出典データセット
uspto-grants-2013_07
特許番号
US08492381B2

反応ノート

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