2,6-Lutidine → (E)-2-((2R,3S,4R,5R)-5-(4-benzamido-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3,4-dihydroxy-tetrahydrofuran-2-yl)vinylphosphonic acid

HRID 2191036Notes

Reaction equation

HRID 2191036 reaction equation
[C:1]([NH:9][C:10]1[N:15]=[CH:14][N:13]=[C:12]2[N:16]([C@@H:19]3[O:23][C@H:22](/[CH:24]=[CH:25]/[P:26](=[O:33])([O:30]CC)[O:27]CC)[C@@H:21]([OH:34])[C@H:20]3[OH:35])[N:17]=[CH:18][C:11]=12)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C(C)=CC=CC=1C.[Si](I)(C)(C)C>CC#N>[C:1]([NH:9][C:10]1[N:15]=[CH:14][N:13]=[C:12]2[N:16]([C@@H:19]3[O:23][C@H:22](/[CH:24]=[CH:25]/[P:26](=[O:27])([OH:30])[OH:33])[C@@H:21]([OH:34])[C@H:20]3[OH:35])[N:17]=[CH:18][C:11]=12)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 85247Trimethylsilyl iodideHCID 59289252diethyl (E)-2-((2R,3S,4R,5R)-5-(4-benzamido-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3,4-dihydroxy-tetrahydrofuran-2-yl)vinylphosphonate

Product 1

HCID 59289371(E)-2-((2R,3S,4R,5R)-5-(4-benzamido-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3,4-dihydroxy-tetrahydrofuran-2-yl)vinylphosphonic acidYield 35%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Compound 25.1 (62.2 mg, 0.124 mmol) in CH3CN (1.25 mL, 0.1 M) was treated with 2,6-lutidine (215 μL, 1.85 mmol) and TMSI (176 μL, 1.24 mmol). The mixture was stirred at room temperature for 1 h and the solvent was removed in vacuo. The residue was treated with concentrated NH4OH (2 mL) and the solvent was removed in vacuo (×3). The residue was treated with 1% AcOH (2 mL) and treated to reverse phase HPLC to afford compound 25.2 (19.3 mg, 35% yield) as a white solid: MS (ESI) m/z 448 [M+H]+.

Workup

  1. customthe solvent was removed in vacuo
  2. additionThe residue was treated with concentrated NH4OH (2 mL)
  3. customthe solvent was removed in vacuo (×3)
  4. additionThe residue was treated with 1% AcOH (2 mL)
  5. additiontreated

Sources & evidence

ORD record
ord-3ab6d7e96a924b10b4e8a19800b61e96
Source dataset
uspto-grants-2012_12
Patent number
US08324179B2

Reaction notes

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