Phosphorus tribromide → N9-cyclohexylethyl-8-bromomethyladenine

HRID 898099Notes

Reaction equation

HRID 898099 reaction equation
[CH:1]1([CH2:7][CH2:8][N:9]2[C:17]([C:18](OC)=O)=[N:16][C:15]3[C:10]2=[N:11][CH:12]=[N:13][C:14]=3[NH2:22])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Al+3].[Li+].[H-].[H-].[H-].C1(CCN2C(CO)=NC3C2=NC=NC=3N)CCCCC1.P(Br)(Br)[Br:50]>O1CCCC1.C(Cl)Cl>[CH:1]1([CH2:7][CH2:8][N:9]2[C:17]([CH2:18][Br:50])=[N:16][C:15]3[C:10]2=[N:11][CH:12]=[N:13][C:14]=3[NH2:22])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 24614Phosphorus tribromideHCID 21226445Aluminium lithium hydrideHCID 53681681N9-cyclohexylethyl-8-hydroxymethyladenineHCID 54390366N9-cyclohexylethyl-8-methoxycarbonyladenine

Product 1

HCID 54368200N9-cyclohexylethyl-8-bromomethyladenine

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

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
  2. customgive N9-cyclohexylethyl-8-hydroxymethyladernine as a white solid
  3. extractionExtraction and chromatography

Sources & evidence

ORD record
ord-16e61c8ef05d418082e2f88e28b5aaf5
Source dataset
uspto-grants-2008_04
Patent number
US07351399B2

Reaction notes

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