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

HRID 476131Notes

Reaction equation

HRID 476131 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([N:8]([CH:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)[C@@H:9]([C:12]2O[CH:14]=[N:15][N:16]=2)[CH2:10][CH3:11])[C:5]([N+:22]([O-])=O)=[CH:4][N:3]=1.C(O)(=O)C>CO.[Zn]>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[N:22]3[CH:14]=[N:15][N:16]=[C:12]3[C@@H:9]([CH2:10][CH3:11])[N:8]([CH:17]3[CH2:21][CH2:20][CH2:19][CH2:18]3)[C:6]=2[N:7]=1

Participants

5

Reactant 2

HCID 176Acetic AcidHCID 86667882HCID 86667882, compound

Product 1

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

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 887MethanolSolvent

Procedure

2-chloro-N-cyclopentyl-5-nitro-N-[(1R)-1-(1,3,4-oxadiazol-2-yl)propyl]pyrimidin-4-amine (37 mg, 0.1049 mmol) in methanol (1.850 mL) was treated with zinc (116.6 mg, 16.35 μL, 1.783 mmol) and then dropwise acetic acid (245.7 mg, 232.7 μL, 4.091 mmol). The reaction was stirred at ambient temperature for 10 minutes. The reaction was filtered and the residual zinc washed with methanol. The combined filtrates were concentrated and re-dissolved in acetic acid (2 mL) and stirred at 70° C. for 1 hour. The reaction was filtered and precipitate washed with methanol. The filtrates were concentrated to dryness under reduced pressure, taken into 10% MeOH/DCM and passed through a short silica gel column. The residue was trituated with ether and the title compound isolated by filtration as a pale brown solid (21 mg, 66%); 1H NMR (400.0 MHz, DMSO) d 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 (+) 305.7.

Workup

  1. filtrationThe reaction was filtered
  2. washthe residual zinc washed with methanol
  3. concentrationThe combined filtrates were concentrated
  4. dissolutionre-dissolved in acetic acid (2 mL)
  5. stirringstirred at 70° C. for 1 hour
  6. filtrationThe reaction was filtered
  7. washprecipitate washed with methanol
  8. concentrationThe filtrates were concentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-83ba881d27814dc5bc257a627425b698
Source dataset
uspto-grants-2014_01
Patent number
US08637666B2

Reaction notes

Loading…