Benzylamine → 2-Chloro-6-benzylamino-9-(2-propynyl)purine

HRID 870307Notes

Reaction equation

HRID 870307 reaction equation
N1C=CN=N1.[N-]=[N+]=[N-].ClC1N=[C:17]2[C:13](NC=N2)=[C:12](Cl)N=1.C(N)C1C=CC=CC=1.[Cl:28][C:29]1[N:37]=[C:36]2[C:32]([NH:33][CH:34]=[N:35]2)=[C:31]([NH:38][CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[N:30]=1.C(Br)C#C>CS(C)=O>[Cl:28][C:29]1[N:37]=[C:36]2[C:32]([N:33]=[CH:34][N:35]2[CH2:17][C:13]#[CH:12])=[C:31]([NH:38][CH2:39][C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=2)[N:30]=1

Participants

8

Reactant 6

HCID 7504BenzylamineHCID 7842Propargyl bromideHCID 33558AzideHCID 53244122,6-Dichloropurine2×HCID 10777711N-Benzyl-2-chloro-9H-purin-6-amine2×HCID 178418936HCID 178418936, compound

Product 1

HCID 889199282-Chloro-6-benzylamino-9-(2-propynyl)purine

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

In one example of the application, a triazole and its fluorinated derivatives can be prepared by a Cu(I)-catalyzed 1,3-dipolar cycloaddition reaction of the corresponding alkyne and azide substrates. As shown below in Scheme 1, synthesis can begin with the reaction of 2,6-dichloropurine (Compound 3) with benzylamine (a) as described, for example, by Oumata, N. et al., Org. Process Res. Dev. 13:641-644 (2009). Using the conditions set forth in the Example below, the reaction can be completed in about 15 minutes at about 60° C. 2-chloro-6-benzylaminopurine (Compound 4) can be propargylated using propargyl bromide in DMSO under mild conditions to yield 2-chloro-6-benzylamino-9-(2-propynyl) purine (Compound 5). The Cu(I)-catalyzed azide-alyne click reaction (as described, for example, by Amblard, F. et al., Chem. Rev. 109:4207-4220, 2009) of 2-chloro-6-benzylamino-9-(2-propynyl) purine (Compound 5) with fluorinated benzyl azides (which can be prepared in situ from their corresponding benzyl bromides) can then yield 1,4-disubstituted triazoles or, more specifically, 2-chloro-6-benzylamino-9-[1-(2-fluorobenzyl)-1H-1,2,3-triazol-4-yl-methyl]purine (Compound 7), 2-chloro-6-benzylamino-9-[1-(2,6-difluorobenzyl)-1H-1,2,3-triazol-4-yl-methyl]purine (Compound 8), and 2-chloro-6-benzylamino-9-[1-(pentafluorobenzyl)-1H-1,2,3-triazol-4-yl-methyl]purine (Compound 9).

Workup

  1. customAs shown below in Scheme 1, synthesis
  2. customthe reaction

Sources & evidence

ORD record
ord-10085e443aa1422f928f6ce9c3470c56
Source dataset
uspto-grants-2015_03
Patent number
US08969556B2

Reaction notes

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