3-Benzyloxy-phenylboronic acid → 3-[3-(benzyloxy)phenyl]-1-cyclopentyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine

HRID 897506노트

반응식

HRID 897506 반응식
[CH:1]1([N:6]2[C:10]3=[N:11][CH:12]=[N:13][C:14]([NH2:15])=[C:9]3[C:8](I)=[N:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:17]([O:24][C:25]1[CH:26]=[C:27](B(O)O)[CH:28]=[CH:29][CH:30]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.O.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.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>[CH2:17]([O:24][C:25]1[CH:30]=[C:29]([C:8]2[C:9]3[C:10](=[N:11][CH:12]=[N:13][C:14]=3[NH2:15])[N:6]([CH:1]3[CH2:5][CH2:4][CH2:3][CH2:2]3)[N:7]=2)[CH:28]=[CH:27][CH:26]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

참가 물질

7

반응물 3

HCID 27343133-Benzyloxy-phenylboronic acidHCID 2735133Sodium Carbonate MonohydrateHCID 223468081-cyclopentyl-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine

생성물 1

HCID 223472053-[3-(benzyloxy)phenyl]-1-cyclopentyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine수율 12.3%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 80711,2-Dimethoxyethane용매

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온도
85 °C

실험 절차

To a mixture of 1-cyclopentyl-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.200 g, 0.631 mmol, 1 equiv) and 3-(benzyloxy)phenylboronic acid (0.110 g, 0.487 mmol, 1.0 equiv) in DME (6 mL) was added tetrakis(triphenylphosphine)palladium (0.044 g, 0.038 mmol, 0.07 equiv) and a solution of sodium carbonate monohydrate (0.187 g, 1.51 mmol, 2.4 equiv) in water (2 mL). The mixture was heated at 85° C. for 16 h, then allowed to cool to ambient temperature. The solvent was removed under reduced pressure and the residue was partitioned between EtOAc (50 mL) and water (50 mL). The organic layer was dried over MgSO4, filtered, and concentrated to afford an oily red-orange solid. Recrystallization from hot EtOAc afforded a red-orange solid which was purified by preparative RP-HPLC (Rainin C18, 8 μm, 300 Å, 25 cm; 10%-60% acetonitrile-0.1M ammonium acetate over 20 min, 21 mL/min). The acetonitrile was removed in vacuo and the aqueous mixture was lyopholyzed to afford 3-[3-(benzyloxy)phenyl]-1-cyclopentyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine as a white solid (0.023 g, 0.060 mmol): 1H NMR (d6 CDCl3, 400 MHz): δH 8.34 (1H, s), 7.27-7.46 (8H, m), 7.07-7.10 (1H, m), 5.63 (2H, bs), 5.31 (1H, quint, J=7.6 Hz), 5.16 (2H, s), 2.15-2.20 (4H, m), 1.96-2.01 (2H, m), 1.72-1.75 (2H, m); RP-HPLC (Hypercil C18, 5 μm, 100 Å, 15 cm; 5%-100% acetonitrile-0.1M ammonium acetate over 15 min, 1 mL/min) Rt 14.00 min. MS: MH+ 386.

후처리

  1. temperatureto cool to ambient temperature
  2. customThe solvent was removed under reduced pressure
  3. customthe residue was partitioned between EtOAc (50 mL) and water (50 mL)
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto afford an oily red-orange solid
  8. customRecrystallization from hot EtOAc
  9. customafforded a red-orange solid which
  10. customwas purified by preparative RP-HPLC (Rainin C18, 8 μm, 300 Å, 25 cm; 10%-60% acetonitrile-0.1M ammonium acetate over 20 min, 21 mL/min)
  11. customThe acetonitrile was removed in vacuo

출처 및 근거

ORD 기록
ord-79f50f3715d2410fa36136225f956a36
출처 데이터셋
uspto-grants-2005_07
특허 번호
US06921763B2

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