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Potassium Carbonate → 1,1-dimethylethyl (2S)-4-[(5'-{[({3-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]phenyl}carbonyl)amino]methyl}-2'-methyl-3-biphenylyl)methyl]-2-methyl-1-piperazinecarboxylate

HRID 564585
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HRID 564585 반응식
Br[C:2]1[CH:3]=[C:4]([CH2:9][NH:10][C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([NH:21][CH2:22][C:23]3[C:24]([NH:36][CH:37]4[CH2:42][CH2:41][O:40][CH2:39][CH2:38]4)=[C:25]4[CH:33]=[N:32][N:31]([CH2:34][CH3:35])[C:26]4=[N:27][C:28]=3[CH2:29][CH3:30])=[O:20])[CH:14]=2)=[O:12])[CH:5]=[CH:6][C:7]=1[CH3:8].[CH3:43][C@H:44]1[CH2:49][N:48]([CH2:50][C:51]2[CH:56]=[CH:55][CH:54]=[C:53](B3OC(C)(C)C(C)(C)O3)[CH:52]=2)[CH2:47][CH2:46][N:45]1[C:66]([O:68][C:69]([CH3:72])([CH3:71])[CH3:70])=[O:67].C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.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>[CH2:34]([N:31]1[C:26]2=[N:27][C:28]([CH2:29][CH3:30])=[C:23]([CH2:22][NH:21][C:19]([C:15]3[CH:14]=[C:13]([C:11]([NH:10][CH2:9][C:4]4[CH:5]=[CH:6][C:7]([CH3:8])=[C:2]([C:55]5[CH:54]=[CH:53][CH:52]=[C:51]([CH2:50][N:48]6[CH2:47][CH2:46][N:45]([C:66]([O:68][C:69]([CH3:72])([CH3:71])[CH3:70])=[O:67])[C@@H:44]([CH3:43])[CH2:49]6)[CH:56]=5)[CH:3]=4)=[O:12])[CH:18]=[CH:17][CH:16]=3)=[O:20])[C:24]([NH:36][CH:37]3[CH2:42][CH2:41][O:40][CH2:39][CH2:38]3)=[C:25]2[CH:33]=[N:32]1)[CH3:35]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

8

반응물 3

HCID 11430Potassium CarbonateHCID 578132571,1-dimethylethyl (2S)-2-methyl-4-{[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methyl}-1-piperazinecarboxylateHCID 57813288N-[(3-Bromo-4-methylphenyl)methyl]-N'-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-1,3-benzenedicarboxamide

생성물 1

HCID 67006781
1,1-dimethylethyl (2S)-4-[(5'-{[({3-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]phenyl}carbonyl)amino]methyl}-2'-methyl-3-biphenylyl)methyl]-2-methyl-1-piperazinecarboxylate

시약·촉매·용매 4

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

실험 절차

N-[(3-Bromo-4-methylphenyl)methyl]-N′-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-1,3-benzenedicarboxamide (0.032 g, 0.05 mmol), 1,1-dimethylethyl (2S)-2-methyl-4-{[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methyl}-1-piperazinecarboxylate (0.0316 g, 0.076 mmol), potassium carbonate (0.021 g, 0.15 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.0029 g, 0.0025 mmol) were combined in dioxane (1.5 mL) and water (0.5 mL). The mixture was microwaved at 150° C. for 30 min. Then the reaction mixture was diluted with EtOAc and washed with H2O 3×. The organic phase was dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified via CombiFlash on a 12 g column eluted with 0-10% MeOH/CH2Cl2 to give 1,1-dimethylethyl (2S)-4-[(5′-{[({3-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]phenyl}carbonyl)amino]methyl}-2′-methyl-3-biphenylyl)methyl]-2-methyl-1-piperazinecarboxylate. This was taken up in 10% TFA/CH2Cl2 (2 mL) and stirred at room temperature for 3 h. The solvents were pumped off, and the crude product was purified using a Gilson HPLC with a TFA system. The purified compound was taken up in EtOAc, washed 3× with 2.5 N NaOH, 1× with brine, dried over anhydrous Na2SO4, filtered, and concentrated to give the title compound as a white solid. LC-MS m/z 743.2 (M+H)+, 1.40 min (ret time); mp 115-118° C. Analytical HPLC shows 100% purity, (ret time 10.211 min).

후처리

  1. customThe mixture was microwaved at 150° C. for 30 min
  2. washwashed with H2O 3×
  3. dry with materialThe organic phase was dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified via CombiFlash on a 12 g column
  7. washeluted with 0-10% MeOH/CH2Cl2

출처 및 근거

ORD 기록
ord-f4891d8779934491ba180cb404d1dde6
출처 데이터셋
uspto-grants-2011_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08067408B2

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