Cesium carbonate → HCID 24944880, compound

HRID 1157426Notes

Reaction equation

HRID 1157426 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].[Cl:21][C:22]1[CH:23]=[C:24](B(O)O)[CH:25]=[CH:26][C:27]=1[Cl:28].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:25]2[CH:24]=[CH:23][C:22]([Cl:21])=[C:27]([Cl:28])[CH:26]=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 27343303,4-Dichlorobenzeneboronic acid

Product 1

HCID 24944880HCID 24944880, compoundYield 11.6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

A solution of 2-iodo adenosine (200 mg, 0.51 mmol), 3,4-dichlorophenylboronic acid (116 mg, 0.61 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 30 s) for 110 min. The solvents were then removed in vacuo and the residue dissolved in EtOAc (30 mL) and washed with sat. aq. NaHCO3 (20 mL×2) and brine (20 mL) and dried over MgSO4. Purification by flash column chromatography (normal phase, ICN silica, 20 g, 18-32%, gradient 2.5-20% ethanol in DCM, residue dry loaded) and twice by reverse phase prep HPLC (Phenomenex Synergi, RP-Hydro 150×10 mm, 10μ, 20 mL per min, gradient 5-100% acetonitrile in water over 10 min, product eluted in 48% 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 50% acetonitrile) afforded (2R,3R,4S,5R)-2-{6-amino-2-(3,4-dichlorophenyl)-9H-purin-9-yl}-5-(hydroxymethyl)tetrahydrofuran-3,4-diol 9 as a white solid (24.4 mg, 11%).

Workup

  1. customThe solvents were then removed in vacuo
  2. dissolutionthe residue dissolved in EtOAc (30 mL)
  3. washwashed with sat. aq. NaHCO3 (20 mL×2) and brine (20 mL)
  4. dry with materialdried over MgSO4
  5. customPurification
  6. dry with materialby flash column chromatography (normal phase, ICN silica, 20 g, 18-32%, gradient 2.5-20% ethanol in DCM, residue dry loaded)
  7. washtwice by reverse phase prep HPLC (Phenomenex Synergi, RP-Hydro 150×10 mm, 10μ, 20 mL per min, gradient 5-100% acetonitrile in water over 10 min, product eluted in 48% 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 50% acetonitrile)

Sources & evidence

ORD record
ord-46bad0641e364662afd6be0c27f1a323
Source dataset
uspto-grants-2010_10
Patent number
US07807685B2

Reaction notes

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