Tetrahydrofuran → (R)-7-chloro-5-cyclopentyl-4-ethyl-4,5-dihydro-[1,2,4]triazolo[4,3-f]pteridine

HRID 39334Notes

Reaction equation

HRID 39334 reaction equation
[Cl:1][C:2]1[N:11]=[CH:10][C:9]2[NH:8][C:7](=O)[C@@H](CC)[N:5]([CH:15]3[CH2:19][CH2:18][CH2:17][CH2:16]3)[C:4]=2[N:3]=1.[NH2:20][NH2:21].[CH2:22]1[CH2:26]O[CH2:24][CH2:23]1.C(OCC)(=O)C>P(Cl)(Cl)(Cl)=O>[Cl:1][C:2]1[N:11]=[CH:10][C:9]2[N:8]3[CH:7]=[N:20][N:21]=[C:24]3[C@@H:23]([CH2:22][CH3:26])[N:5]([CH:15]3[CH2:19][CH2:18][CH2:17][CH2:16]3)[C:4]=2[N:3]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 8857Ethyl AcetateHCID 9321HydrazineHCID 24739252(R)-2-chloro-8-cyclopentyl-7-ethyl-7,8-dihydropteridin-6(5H)-one

Product 1

HCID 59389586(R)-7-chloro-5-cyclopentyl-4-ethyl-4,5-dihydro-[1,2,4]triazolo[4,3-f]pteridineYield 63%

Reagents, catalysts & solvents 1

HCID 24813Phosphorus oxychlorideSolvent

Procedure

(R)-2-Chloro-8-cyclopentyl-7-ethyl-7,8-dihydropteridin-6(5H)-one (100 mg, 0.357 mmol) in phosphorus oxychloride (3.0 ml) was stirred at 110° C. for 3 hours then concentrated under reduced pressure. The residue was dissolved in anhydrous dichloromethane and added dropwise to 1.0 M hydrazine in THF (3.6 ml, 3.57 mmol). The mixture was stirred at RT overnight, taken into ethyl acetate and washed with aqueous sodium hydrogen carbonate, dried over magnesium sulphate and concentrated. The residue of crude hydrazide was dissolved in trimethyl orthoformate (2.0 ml) and stirred at 110° C. for 90 min. The mixture was concentrated under reduced pressure and purified by flash chromatography on silica gel eluting with ethyl acetate to give (R)-7-chloro-5-cyclopentyl-4-ethyl-4,5-dihydro-[1,2,4]triazolo[4,3-f]pteridine (68 mg, 63%) as a pale brown solid; 1H NMR (DMSO D6) 0.75 (3H, t), 1.50-1.64 (2H, m), 1.80-2.08 (8H, m), 4.22-4.33 (1H, m), 5.28-5.35 (1H, m), 8.68 (1H, s), 9.35 (1H, s); MS (ES+) 305.

Workup

  1. concentrationthen concentrated under reduced pressure
  2. dissolutionThe residue was dissolved in anhydrous dichloromethane
  3. washwashed with aqueous sodium hydrogen carbonate
  4. dry with materialdried over magnesium sulphate
  5. concentrationconcentrated
  6. dissolutionThe residue of crude hydrazide was dissolved in trimethyl orthoformate (2.0 ml)
  7. stirringstirred at 110° C. for 90 min
  8. concentrationThe mixture was concentrated under reduced pressure
  9. custompurified by flash chromatography on silica gel eluting with ethyl acetate

Sources & evidence

ORD record
ord-bc61d9880e714e42b1223595d38d8291
Source dataset
uspto-grants-2013_09
Patent number
US08524902B2

Reaction notes

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