Piperidine → 2-{[(1S)-1-Methylbutyl]oxy}-8-(methyloxy)-9-[5-(1-piperidinyl)pentyl]-9H-purin-6-amine

HRID 2367966Notes

Reaction equation

Cl[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][N:7]1[C:15]([O:16][CH3:17])=[N:14][C:13]2[C:8]1=[N:9][C:10]([O:19][C@@H:20]([CH3:24])[CH2:21][CH2:22][CH3:23])=[N:11][C:12]=2[NH2:18].C(N(CC)CC)C.[NH:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1>CN(C=O)C>[CH3:24][C@H:20]([O:19][C:10]1[N:9]=[C:8]2[C:13]([N:14]=[C:15]([O:16][CH3:17])[N:7]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][N:32]2[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]2)=[C:12]([NH2:18])[N:11]=1)[CH2:21][CH2:22][CH3:23]

Participants

Conditions

Temperature: 70 °C

Procedure

9-(5-Chloropentyl)-2-{[(1S)-1-methylbutyl]oxy}-8-(methyloxy)-9H-purin-6-amine (for example, as prepared for Intermediate 8) (80 mg, 0.225 mmol), triethylamine (0.031 mL, 0.225 mmol) and piperidine (0.045 mL, 0.45 mmol) were suspended in DMF (3 mL) and the mixture heated to 70° C. for 18 hours. The solvent was removed and the residue partitioned between dichloromethane (4 mL) and saturated sodium bicarbonate (4 mL). The aqueous phase was re-extracted with further dichloromethane and the combined organic extracts were concentrated and the residue dissolved in 1:1 methanol:DMSO (1 mL) and purified by MDAP (Method A). The product-containing fractions were combined and evaporated under a stream of nitrogen to give the title compound (47.2 mg).

Workup

customThe solvent was removed
customthe residue partitioned between dichloromethane (4 mL) and saturated sodium bicarbonate (4 mL)
extractionThe aqueous phase was re-extracted with further dichloromethane
concentrationthe combined organic extracts were concentrated
dissolutionthe residue dissolved in 1:1 methanol
customDMSO (1 mL) and purified by MDAP (Method A)
customevaporated under a stream of nitrogen

Sources & evidence

ORD record: ord-be7f3331ae5f4d6f8cc2d8c4c2916c2f
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08703754B2

Reaction notes

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