Acetonitrile → HCID 86640484, compound

HRID 1920697Notes

Reaction equation

HRID 1920697 reaction equation
[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:11]2[O:15][C@H:14]([CH2:16][OH:17])[C@@H:13]([OH:18])[C@:12]2([F:20])[CH3:19])=[C:4]([N:21]2[CH2:24][CH2:23][CH2:22]2)[N:3]=1.N1C=NN=N1.C(#N)C.C(N([CH:40]([O:48][P:49](N)[O-:50])N(C(C)C)C(C)C)C(C)C)(C)C>N1C=CC=CC=1>[P:49]([OH:50])([OH:15])[OH:48].[N:21]1([C:4]2[N:3]=[C:2]([NH2:1])[N:10]=[C:9]3[C:5]=2[N:6]=[CH:7][N:8]3[C@@H:11]2[O:15][C@H:14]3[C@@H:13]([O:18][P:49]([O:48][CH3:40])[O:17][CH2:16]3)[C@:12]2([F:20])[CH3:19])[CH2:24][CH2:23][CH2:22]1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 46843958HCID 46843958, compoundHCID 86640486HCID 86640486, compoundHCID 178418441HCID 178418441, compound

Product 1

HCID 86640484HCID 86640484, compoundYield 12%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

(2R,3R,4R,5R)-5-(2-Amino-6-azetidin-1-yl -purin-9-yl)-4-fluoro-2-hydroxymethyl-4-methyl-tetrahydro-furan-3-ol (14, 340 mg, 1.0 mmol) was dissolved in anhydrous pyridine (6 ml) at ambient temperature. A solution of 0.45 M 1H -tetrazole in acetonitrile (5.5 mL, 2.5 mmol) was added followed by bis (N,N-diisopropylamino)methylphosphoramidite (317 μL, 1.1 mmol). The mixture was stirred at ambient temperature for 17 h. The solvent was concentrated under reduced pressure and the residue was triturated with ethyl acetate (20 mL). The resulting precipitant of salts was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using a gradient of ethyl acetate in hexanes (40-80%). The product containing fractions were combined and concentrated to a white solid, 47 mg (12% yield).

Workup

  1. concentrationThe solvent was concentrated under reduced pressure
  2. customthe residue was triturated with ethyl acetate (20 mL)
  3. customThe resulting precipitant of salts was removed by filtration
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography
  6. additionThe product containing fractions
  7. concentrationconcentrated to a white solid, 47 mg (12% yield)

Sources & evidence

ORD record
ord-2b3fd76ae1d94718977b5e8e483c2f30
Source dataset
uspto-grants-2012_05
Patent number
US08173621B2

Reaction notes

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