Cesium fluoride → HCID 178461552, compound

HRID 876517Notes

Reaction equation

HRID 876517 reaction equation
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

Participants

6

Reactant 3

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

Product 1

HCID 178461552HCID 178461552, compoundYield 47%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
115 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-361bff02d0ff49b288ea54eab87d5403
Source dataset
uspto-grants-2015_03
Patent number
US08987257B2

Reaction notes

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