Sodium Carbonate → 3-((4-amino-3-(3-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-2-isopropyl-8-methylisoquinolin-1(2H)-one

HRID 1046751노트

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HRID 1046751 반응식
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:12][C:13]3[N:14]([CH:25]([CH3:27])[CH3:26])[C:15](=[O:24])[C:16]4[C:21]([CH:22]=3)=[CH:20][CH:19]=[CH:18][C:17]=4[CH3:23])[N:9]=[C:10](I)[C:3]=12.CC1(C)C(C)(C)OB([C:36]2[CH:37]=[C:38]([OH:42])[CH:39]=[CH:40][CH:41]=2)O1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.C(O)C.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:12][C:13]3[N:14]([CH:25]([CH3:27])[CH3:26])[C:15](=[O:24])[C:16]4[C:21]([CH:22]=3)=[CH:20][CH:19]=[CH:18][C:17]=4[CH3:23])[N:9]=[C:10]([C:36]3[CH:41]=[CH:40][CH:39]=[C:38]([OH:42])[CH:37]=3)[C:3]=12

참가 물질

7

반응물 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 27346233-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 580088813-((4-Amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-2-isopropyl-8-methylisoquinolin-1(2H)-one

생성물 1

HCID 580089843-((4-amino-3-(3-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-2-isopropyl-8-methylisoquinolin-1(2H)-one수율 61%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 86633292ethanol water DMF용매

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온도
100 °C

실험 절차

To a stirred mixture of 3-((4-Amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-2-isopropyl-8-methylisoquinolin-1(2H)-one (2008) (95 mg, 0.2 mmol) and 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (66 mg, 0.3 mmol) in DMF-EtOH—H2O (3:1:1, 20 mL), Pd(OAc)2 (16 mg, 0.075 mmol), PPh3 (39.3 mg 0.15 mmol) and Na2CO3 (132 mg, 1.25 mmol) were added sequentially. The resulting mixture was degassed and back-filled with argon three times and then stirred at 100° C. for 1 h. The mixture was allowed to cool to RT, filtered through silica gel (10 g) and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (2-20% MeOH/DCM) to afford the product, 3-((4-amino-3-(3-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-2-isopropyl-8-methylisoquinolin-1(2H)-one (2009, compound 62 in Table 4) (53 mg, 61% yield) as a slightly yellow solid.

후처리

  1. additionwere added sequentially
  2. customThe resulting mixture was degassed
  3. additionback-filled with argon three times
  4. temperatureto cool to RT
  5. filtrationfiltered through silica gel (10 g)
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash column chromatography on silica gel (2-20% MeOH/DCM)

출처 및 근거

ORD 기록
ord-051369e921e342fba65d4f9643bbf87a
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08569323B2

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