Dimethylformamide → N9-cyclohexylethyl-8-diethylphosphonomethoxy-methyladenine

HRID 898100Notes

Reaction equation

HRID 898100 reaction equation
[CH:1]1([CH2:7][CH2:8][N:9]2[C:17](CBr)=[N:16][C:15]3[C:10]2=[N:11][CH:12]=[N:13][C:14]=3[NH2:20])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Na].[OH:22][CH2:23][P:24](=[O:31])([O:28][CH2:29][CH3:30])[O:25][CH2:26][CH3:27].[CH3:32]N(C=O)C>>[CH:1]1([CH2:7][CH2:8][N:9]2[C:17]([O:22][CH2:23][P:24]([O:28][CH2:29][CH3:30])([O:25][CH2:26][CH3:27])=[O:31])=[N:16][C:15]3[C:10]2=[N:11][C:12]([CH3:32])=[N:13][C:14]=3[NH2:20])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 3

HCID 6228Dimethylformamide2×HCID 54368200N9-cyclohexylethyl-8-bromomethyladenineHCID 86585098Diethyl hydroxymethylphosphonate sodium salt

Product 1

HCID 86585097N9-cyclohexylethyl-8-diethylphosphonomethoxy-methyladenine

Procedure

A mixture of N9-cyclohexylethyl-8-bromoadenine (1 mmol), tetrakis (triphenylphosphine)palladium (0.05 mmol), and triethylamine (5 mmol) in DMF in a sealed tube was warmed at 110° C. under 50 psi of carbon monoxide. After 24 h the cooled reaction mixture was evaporated and purified through chromatography to give N9-cyclohexylethyl-8-methoxycarbonyladenine as a yellow solid. Step B. A solution of N9-cyclohexylethyl-8-methoxycarbonyladenine (1 mmol) in tetrahydrofuran was treated with lithium aluminum hydride (1 mmol) at 0° C. for 1 h. Extraction and chromatography give N9-cyclohexylethyl-8-hydroxymethyladernine as a white solid. Step C. A solution of N9-cyclohexylethyl-8-hydroxymethyladenine (1 mmol) in methylene chloride was treated with PBr3 (1 mmol) at 25° C. for 1 h. Extraction and chromatography give N9-cyclohexylethyl-8-bromomethyl-adenine as a white solid. Step D. A solution of N9-cyclohexylethyl-8-bromomethyladenine (1 mmol) in DMF was treated with a solution of diethyl hydroxymethylphosphonate sodium salt (1 mmol) in DMF at 25° C. for 1 h. Extraction and chromatography gave N9-cyclohexylethyl-8-diethylphosphonomethoxy-methyladenine as a white solid. Step E. N9-cyclohexylethyl-8-diethylphosphonomethoxymethyladenine was subjected to Step F in Example 1.

Workup

  1. extractionExtraction and chromatography

Sources & evidence

ORD record
ord-974df673e93741608236e814649207ae
Source dataset
uspto-grants-2008_04
Patent number
US07351399B2

Reaction notes

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