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Acetonitrile → 2-amino-5-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanylethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-N,N-dimethyl-benzamide

HRID 2388970
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HRID 2388970 반응식
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15](B3OC(C)(C)C(C)(C)O3)[CH:16]=2)[N:11]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[N:10]=1.[NH2:35][C:36]1[CH:46]=[CH:45][C:44](Br)=[CH:43][C:37]=1[C:38]([N:40]([CH3:42])[CH3:41])=[O:39].C(#N)C.C(=O)(O)[O-].[Na+]>C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe].O.ClCCl>[NH2:35][C:36]1[CH:46]=[CH:45][C:44]([C:15]2[CH:16]=[C:17]3[C:9]([C:4]4[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=4[O:2][CH3:1])=[N:10][N:11]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:32])[CH3:33])[C:12]3=[N:13][CH:14]=2)=[CH:43][C:37]=1[C:38]([N:40]([CH3:42])[CH3:41])=[O:39]
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참가 물질

8

반응물 4

HCID 6342AcetonitrileHCID 516892Sodium BicarbonateHCID 509995122-Amino-5-bromo-N,N-dimethylbenzamideHCID 598360923-(2-methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(2-trimethylsilanyl-ethoxy-methyl)-1H-pyrazolo[3,4-b]pyridine

생성물 1

HCID 579757432-amino-5-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanylethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-N,N-dimethyl-benzamide
수율 33.3%

시약·촉매·용매 3

HCID 53485975CID 53485975촉매HCID 962Water용매HCID 6344Dichloromethane용매

실험 절차

650 mg (1.35 mmol) of 3-(2-methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridine, 395 mg (1.62 mmol) 2-amino-5-bromo-N,N-dimethyl-benzamide and 55 mg (67 μmol) of dichloro[1,1′-bis(diphenylphoshino)ferrocene]palladium(II) dichloromethane adduct were placed in a vial. 8 mL of acetonitrile and 8 mL of a saturated aqueous solution of sodium bicarbonate were added. The vial was closed and the mixture irradiated in a Personal Chemistry® Optimizer to 100° C. for 15 min. The crude mixture was distributed between dichloromethane and water. The aqueous layer was extracted three times with dichloromethane. The combined organic phases were dried over sodium sulfate and evaporated. The crude was purified by flash chromatography on silica gel using a gradient of ethyl acetate containing 15% of methanol in hexanes to afford 288 mg (0.45 mmol, 33%) of 2-amino-5-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanylethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-N,N-dimethyl-benzamide as a pale beige solid. MS: m/z 518.1 (M+H+).

후처리

  1. customThe vial was closed
  2. customthe mixture irradiated in a Personal Chemistry® Optimizer to 100° C. for 15 min
  3. extractionThe aqueous layer was extracted three times with dichloromethane
  4. dry with materialThe combined organic phases were dried over sodium sulfate
  5. customevaporated
  6. customThe crude was purified by flash chromatography on silica gel using a gradient of ethyl acetate containing 15% of methanol in hexanes

출처 및 근거

ORD 기록
ord-b473fb104f5249559b1d75fa957dc614
출처 데이터셋
uspto-grants-2012_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08268994B2

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