N,N'-dicyclohexyl-4-morpholinecarboxamidine → [1-[(2-Amino-6-chloro-purin-9-yl)methyl]cyclopropoxy]methylphosphonic acid

HRID 1371275

Reaction equation

HRID 1371275 reaction equation
NC1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[CH2:11][C:12]1([O:15][CH2:16][P:17](=[O:20])([OH:19])[OH:18])[CH2:14][CH2:13]1.C1([NH:27]C(N2CCOCC2)=NC2CCCCC2)CCCCC1.C(OCCl)(=O)C(C)(C)C.CO.Cl[CH2:54][Cl:55]>CN(C)C=O>[NH2:27][C:9]1[N:8]=[C:7]2[C:3]([N:4]=[CH:5][N:6]2[CH2:11][C:12]2([O:15][CH2:16][P:17](=[O:20])([OH:18])[OH:19])[CH2:13][CH2:14]2)=[C:54]([Cl:55])[N:10]=1

Participants

6

Reactant 4

HCID 21079N,N'-dicyclohexyl-4-morpholinecarboxamidineHCID 87885Chloromethyl pivalateHCID 5270770((1-((6-Amino-9H-purin-9-yl)methyl)cyclopropoxy)methyl)phosphonic acidHCID 21226129Dichloromethane methanol

Product 1

HCID 5270772[1-[(2-Amino-6-chloro-purin-9-yl)methyl]cyclopropoxy]methylphosphonic acidYield 32%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The compound prepared in Example 1 (1.00 g) was dissolved in 150 ml of dry dimethylformamide, and 2.08 g (7.32 mmol) of N,N′-dicyclohexyl-4-morpholine-carboxamidine and 2.75 g (18.3 mmol) of chioromethyl pivalate were added thereto. When the reaction mixture became homogeneous after about 1 hour, it was stirred for 5 days at room temperature. The reaction solution was filtered, the filtrate was concentrated under reduced pressure, and the residue was fractionated with 50 ml of water and 50 ml of toluene to separate the organic layer. The aqueous layer was extracted twice with 50 ml of toluene. The combined organic layers were concentrated under reduced pressure. The residue was purified by column chromatography (eluent: methanol/dichloromethane=1/20, v/v) to give 0.59g (Yield 32%) of the title compound as a white solid.

Workup

  1. filtrationThe reaction solution was filtered
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. customto separate the organic layer
  4. extractionThe aqueous layer was extracted twice with 50 ml of toluene
  5. concentrationThe combined organic layers were concentrated under reduced pressure
  6. customThe residue was purified by column chromatography (eluent

Sources & evidence

ORD record
ord-a3b1c84bc88e40f0b038b4454a6fcfb4
Source dataset
uspto-grants-2007_01
Patent number
US07157448B2

Linked notes

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