Cesium fluoride → HCID 178461552, 화합물

HRID 876517노트

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HRID 876517 반응식
Br[C:2]1[NH:3][C:4]2[C:9]([N:10]=1)=[C:8]([N:11]1[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1)[N:7]=[C:6]([N:17]1[CH2:22][C@@H:21]([CH3:23])[O:20][C@@H:19]([CH3:24])[CH2:18]1)[N:5]=2.[F-].[Cs+].[OH:27][C:28]1[CH:29]=[C:30](B(O)O)[CH:31]=[CH:32][CH:33]=1>C(#N)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>[CH3:24][C@@H:19]1[O:20][C@H:21]([CH3:23])[CH2:22][N:17]([C:6]2[N:5]=[C:4]3[C:9]([N:10]=[C:2]([C:32]4[CH:33]=[C:28]([OH:27])[CH:29]=[CH:30][CH:31]=4)[NH:3]3)=[C:8]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)[N:7]=2)[CH2:18]1

참가 물질

6

반응물 3

HCID 25953Cesium fluorideHCID 2734359(3-hydroxyphenyl)boronic AcidHCID 178461551HCID 178461551, 화합물

생성물 1

HCID 178461552HCID 178461552, 화합물수율 47%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 18373917Acetonitrile--water (1/1)용매

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온도
115 °C

실험 절차

To a round bottom flask were added, 8-bromo-2-((2S,6R)-2,6-dimethyl-morpholin-4-yl)-6-morpholin-4-yl-9H-purine (38.2 mg, 0.096 mmol), cesium fluoride 58.4 mg, 0.39 mmol), 3-hydroxyphenylboronic acid (39.8 mg, 0.29 mmol) and tetrakis(triphenylphosphine)palladium (8.9 mg, 7.69 mmol) followed by 1 mL of acetonitrile/water solvent mixture (10/1 ratio). Suspension was heated to 115° C. and stirred overnight. Upon completion of the reaction, the suspension was cooled and solids filtered off. Solvent was removed under reduced pressure and the crude was purified directly by preparative HPLC to provide 3-[2-((2S,6R)-2,6-dimethyl-morpholin-4-yl)-6-morpholin-4-yl-9H-purin-8-yl]-phenol (18.5 mg, 47%) as yellow solid. LC/MS analysis method 7, mass (ES+) m/z 411.2, retention time 1.40 min. 1HNMR (CDCl3): 7.34 (1H, d), 7.24 (2H, m), 6.87 (1H, d), 4.35 (2H, d), 4.30 (4H, brs), 3.80 (4H, m), 3.57 (2H, m), 2.53 (2H, t), 1.16 (6H, d).

후처리

  1. additionTo a round bottom flask were added
  2. customUpon completion of the reaction
  3. temperaturethe suspension was cooled
  4. filtrationsolids filtered off
  5. customSolvent was removed under reduced pressure
  6. customthe crude was purified directly by preparative HPLC

출처 및 근거

ORD 기록
ord-361bff02d0ff49b288ea54eab87d5403
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08987257B2

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