Ethyl Acetate → HCID 86667378, compound

HRID 334167Notes

Reaction equation

HRID 334167 reaction equation
[N:1]([CH:4]([C:6]1[N:7]([CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][O:23]2)[C:8]2[C:13]([N:14]=1)=[C:12]([N:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1)[N:11]=[C:10]([Cl:21])[N:9]=2)[CH3:5])=[N+]=[N-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(OCC)(=O)C.C1(P(=O)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1.O.C(Cl)Cl.CO>[Cl:21][C:10]1[N:9]=[C:8]2[C:13]([N:14]=[C:6]([CH:4]([NH2:1])[CH3:5])[N:7]2[CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][O:23]2)=[C:12]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[N:11]=1

Participants

9

Reactant 4

HCID 8857Ethyl AcetateHCID 11776TriphenylphosphineHCID 13097Triphenylphosphine OxideHCID 86667377HCID 86667377, compound2×

Product 1

HCID 86667378HCID 86667378, compound

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 8-(1-azido-ethyl)-2-chloro-6-morpholin-4-yl-9-(tetrahydro-pyran-2-yl)-9H-purine (0.47 g, 1.20 mmol) in THF (13 mL) and water (4 mL) was added triphenylphosphine (0.33 g, 1.28 mmol). The reaction mixture was heated at 70° C. for 2 h, then cooled to RT. Ethyl acetate was added and the phases were separated. The aqueous phase was extracted three times with ethyl acetate. The combined organic fractions were dried (Na2 SO4), filtered and concentrated in vacuo. The resulting residue, together with crude product from a reaction performed similarly on a smaller scale (0.05 g, 0.14 mmol of 8-(1-azido-ethyl)-2-chloro-6-morpholin-4-yl-9-(tetrahydro-pyran-2-yl)-9H-purine), was subjected to flash chromatography (SiO2) gradient 0-10% methanol in DCM). Eluted material containing title compound and triphenylphosphine oxide was subjected to flash chromatography (SiO2) gradient 0-20% methanol in TBME), and clean material from the two columns was combined to give 1-[2-Chloro-6-morpholin-4-yl-9-(tetrahydro-pyran-2-yl)-9H-purin-8-yl]-ethylamine (0.41 g, 84%, mixture of two pairs of diastereomers). LCMS RT=2.15 min and 2.19 min, [M+H]+=367/369

Workup

  1. temperaturecooled to RT
  2. customthe phases were separated
  3. extractionThe aqueous phase was extracted three times with ethyl acetate
  4. customThe combined organic fractions were dried (Na2 SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-08ab2ac15e2c4a07915f16ccb3fcacb1
Source dataset
uspto-grants-2014_11
Patent number
US08883799B2

Reaction notes

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