p-Toluenesulfonic acid → HCID 86667338, compound

HRID 334120Notes

Reaction equation

[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([I:21])[N:8]2[CH2:11][CH2:12][CH2:13][O:14]C2CCCCO2)=[C:4]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[N:3]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([I:21])[N:8]2[CH2:11][CH2:12][CH2:13][OH:14])=[C:4]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[N:3]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To 4-(2-chloro-8-iodo-9-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-9H-purin-6-yl)morpholine (0.39 g, 0.8 mmol) in methanol (5 mL) was added p-toluenesulfonic acid (10 mg, 0.08 mmol). The reaction was heated at 50° C. for 30 min, whereupon precipitation was observed signaling reaction completion. This was confirmed by analytical LC-MS. The reaction mixture was concentrated in vacuo to give 3-(2-chloro-8-iodo-6-morpholino-9H-purin-9-yl)propan-1-ol. Copper(I) iodide (9 mg, 0.05 mmol), picolinic acid (10 mg, 0.09 mmol) and potassium phosphate (0.4 g, 1.9 mmol) were combined in oven-dried 50-mL round-bottom flask and evacuated/recycled with N2 atmosphere. Subsequently, 3-(2-chloro-8-iodo-6-morpholino-9H-purin-9-yl)propan-1-ol was dissolved in anhydrous dimethyl sulfoxide (6.7 mL) and introduced via syringe. The entire mixture was heated at 80° C. for 20 h. LC-MS indicated good conversion to the desired product. The reaction mixture was cooled to room temperature, diluted with water and EtOAc, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by FCC (40 g silica gel column, 0-100% EtOAc in heptane) to give 112 mg of 2-chloro-4-morpholino-8,9-dihydro-7H-[1,3]oxazino[2,3-e]purine (40%). MS (ESI+): m/z 296.2 (M+H+)

Workup

customreaction completion
concentrationThe reaction mixture was concentrated in vacuo

Sources & evidence

ORD record: ord-46caf90e17e5452f95c5cdc729073d18
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08883799B2

Reaction notes

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