Acetonitrile → HCID 67434459, compound

HRID 2168585Notes

Reaction equation

HRID 2168585 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:30](#N)C.C(N([CH:40]([O:48][P:49](N)[O-])N(C(C)C)C(C)C)C(C)C)(C)C>N1C=CC=CC=1>[CH2:24]([N:21]([CH2:22][CH3:30])[C:4]1[N:3]=[C:2]([NH2:1])[N:10]=[C:9]2[C:5]=1[N:6]=[CH:7][N:8]2[C@@H:11]1[O:15][C@H:14]2[C@@H:13]([O:18][P:49]([O:48][CH3:40])[O:17][CH2:16]2)[C@:12]1([F:20])[CH3:19])[CH3:23]

Participants

6

Reactant 4

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

Product 1

HCID 67434459HCID 67434459, 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 (8, 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-e169027b6c4d425a9484dce470250685
Source dataset
uspto-grants-2015_06
Patent number
US09045520B2

Reaction notes

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