Dimethylformamide → HCID 86667377, compound

HRID 334166Notes

Reaction equation

HRID 334166 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH:17](O)[CH3:18])[N:8]2[CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)=[C:4]([N:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)[N:3]=1.CN(C=O)C.C1(P([N:45]=[N+:46]=[N-:47])(C2C=CC=CC=2)=O)C=CC=CC=1.N12CCCN=C1CCCCC2>C1(C)C=CC=CC=1.C(OCC)(=O)C.C1CCCCC1.O>[N:45]([CH:17]([C:7]1[N:8]([CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)[C:9]2[C:5]([N:6]=1)=[C:4]([N:20]1[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1)[N:3]=[C:2]([Cl:1])[N:10]=2)[CH3:18])=[N+:46]=[N-:47]

Participants

9

Reactant 4

HCID 6228DimethylformamideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 199401P,P-Diphenylphosphinic azideHCID 86667376HCID 86667376, compound2×

Product 1

HCID 86667377HCID 86667377, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8078CyclohexaneSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

1-[2-Chloro-6-morpholin-4-yl-9-(tetrahydro-pyran-2-yl)-9H-purin-8-yl]-ethanol (0.37 g, 1.01 mmol) was dissolved in anhydrous toluene (5.6 mL) and DMF (0.9 mL) and the solution was cooled in ice. Diphenylphosphoryl azide (0.56 mL, 2.54 mmol) was added, followed by dropwise addition of 1,8-diazabicyclo[5.4.0]undec-7-ene (0.37 mL, 2.54 mmol). The reaction mixture was stirred at room temperature for 16 h, then diluted with ethyl acetate followed by water and the phases were separated. The aqueous phase was extracted twice with ethyl acetate and the combined organic fractions were dried (Na2SO4), filtered and concentrated in vacuo. The resulting residue, together with crude product from a reaction performed similarly on a smaller scale (0.10 g, 0.27 mmol of 1-[2-chloro-6-morpholin-4-yl-9-(tetrahydro-pyran-2-yl)-9H-purin-8-yl]-ethanol), was subjected to flash chromatography (SiO2) gradient 0-50% ethyl acetate in cyclohexane to give 8-(1-Azido-ethyl)-2-chloro-6-morpholin-4-yl-9-(tetrahydro-pyran-2-yl)-9H-purine as two separated pairs of diastereomers (0.25 g and 0.27 g, total 0.52 g, 100%). LCMS RT=4.05 min, [M+H]+=393/395. LCMS RT=4.16 min, [M+H]+=393/395

Workup

  1. customthe phases were separated
  2. extractionThe aqueous phase was extracted twice with ethyl acetate
  3. dry with materialthe combined organic fractions were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-99d229472bd64d4e95cd8f322d9f4dd8
Source dataset
uspto-grants-2014_11
Patent number
US08883799B2

Reaction notes

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