Azetidine → 9-[5-(1-Azetidinyl)pentyl]-2-(butyloxy)-8-(methyloxy)-9H-purin-6-amine

HRID 527784Notes

Reaction equation

[CH2:1]([O:5][C:6]1[N:14]=[C:13]2[C:9]([N:10]=[C:11]([O:21][CH3:22])[N:12]2[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]Cl)=[C:8]([NH2:23])[N:7]=1)[CH2:2][CH2:3][CH3:4].[NH:24]1[CH2:27][CH2:26][CH2:25]1.C(N(CC)C(C)C)(C)C>CN(C=O)C>[N:24]1([CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][N:12]2[C:11]([O:21][CH3:22])=[N:10][C:9]3[C:13]2=[N:14][C:6]([O:5][CH2:1][CH2:2][CH2:3][CH3:4])=[N:7][C:8]=3[NH2:23])[CH2:27][CH2:26][CH2:25]1

Participants

Conditions

Temperature: 50 °C

Procedure

2-(Butyloxy)-9-(5-chloropentyl)-8-(methyloxy)-9H-purin-6-amine (100 mg, 0.293 mmol), azetidine (0.020 ml, 0.293 mmol) and N,N-diisopropylethylamine (0.102 ml, 0.585 mmol) were dissolved in DMF (2 ml) and heated at 50° C. for 72 hours. The solvent was removed in vacuo and the residue partitioned between DCM (5 ml) and water (5 ml) and the layers separated using a hydrophobic frit. The aqueous phase was re-extracted with DCM (5 ml) and the combined organic extracts concentrated and the residue dissolved in 1:1 MeOH:DMSO (1 ml) and purified by MDAP (Method A). The product-containing fractions were evaporated under a stream of nitrogen to give the title compound as a clear gum (6.8 mg). LCMS (System B): tRET=1.26 min; MH+=363

Workup

customThe solvent was removed in vacuo
customthe residue partitioned between DCM (5 ml) and water (5 ml)
customthe layers separated
extractionThe aqueous phase was re-extracted with DCM (5 ml)
concentrationthe combined organic extracts concentrated
dissolutionthe residue dissolved in 1:1 MeOH
customDMSO (1 ml) and purified by MDAP (Method A)
customThe product-containing fractions were evaporated under a stream of nitrogen

Sources & evidence

ORD record: ord-4ba53401446b45e19e0974350412a0d6
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346806B2

Reaction notes

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