Cesium carbonate → HCID 24944884, compound

HRID 1157427Notes

Reaction equation

HRID 1157427 reaction equation
I[C:2]1[N:3]=[C:4]([NH2:20])[C:5]2[N:6]=[CH:7][N:8]([C:18]=2[N:19]=1)[C@@H:9]1[O:17][C@H:14]([CH2:15][OH:16])[C@@H:12]([OH:13])[C@H:10]1[OH:11].[F:21][C:22]1[CH:23]=[C:24](B(O)O)[CH:25]=[C:26]([F:28])[CH:27]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C(O)C.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>[NH2:20][C:4]1[N:3]=[C:2]([C:24]2[CH:23]=[C:22]([F:21])[CH:27]=[C:26]([F:28])[CH:25]=2)[N:19]=[C:18]2[C:5]=1[N:6]=[CH:7][N:8]2[C@H:9]1[C@H:10]([OH:11])[C@H:12]([OH:13])[C@@H:14]([CH2:15][OH:16])[O:17]1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 1696622-IodoadenosineHCID 2734338(3,5-Difluorophenyl)boronic acid

Product 1

HCID 24944884HCID 24944884, compoundYield 9%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

A solution of 2-iodo adenosine (200 mg, 0.51 mmol), 3,5-difluorophenylboronic acid (150 mg, 0.95 mmol), cesium carbonate (364 mg, 1.12 mmol) and Pd(PPh3)4 (59 mg, 0.051 mmol) in toluene (1.2 mL) and ethanol (2.4 mL) was heated in a Biotage microwave (120° C., absorption high, pre-stirring 15 s) for 40 min. The solvents were then removed in vacuo and the residue dissolved in EtOAc (20 mL) and washed with sat. aq. NaHCO3 (20 mL×2) and brine (20 mL) and dried over MgSO4. Purification by reverse phase prep HPLC in 2 batches (Phenomenex Synergi, RP-Hydro 150×10 mm, 10%, 20 mL per min, gradient 5-100% acetonitrile in water over 10 min, product eluted in 35% acetonitrile) and (Phenomenex Synergi, RP-Hydro 150×10 mm, 10μ, 20 mL per min, gradient 5-100% acetonitrile in water over 10 min, product eluted in 40% acetonitrile), combination of the purer fractions from both columns, concentration in vacuo to ˜20 mL and filtration of the resulting white precipitate gave (2R,3R,4S,5R)-2-{6-amino-2-(3,5-difluorophenyl)-9H-purin-9-yl}-5-(hydroxymethyl)tetrahydrofuran-3,4-diol 10 as a white solid (16.8 mg, 9%).

Workup

  1. customThe solvents were then removed in vacuo
  2. dissolutionthe residue dissolved in EtOAc (20 mL)
  3. washwashed with sat. aq. NaHCO3 (20 mL×2) and brine (20 mL)
  4. dry with materialdried over MgSO4
  5. customPurification by reverse phase prep HPLC
  6. washin 2 batches (Phenomenex Synergi, RP-Hydro 150×10 mm, 10%, 20 mL per min, gradient 5-100% acetonitrile in water over 10 min, product eluted in 35% acetonitrile) and (Phenomenex Synergi, RP-Hydro 150×10 mm, 10μ, 20 mL per min, gradient 5-100% acetonitrile in water over 10 min, product eluted in 40% acetonitrile), combination of the purer fractions
  7. concentrationfrom both columns, concentration in vacuo
  8. filtrationto ˜20 mL and filtration of the resulting white precipitate

Sources & evidence

ORD record
ord-33ff32909b7a44afb630065eec38dfee
Source dataset
uspto-grants-2010_10
Patent number
US07807685B2

Reaction notes

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