1H-1,2,4-Triazole → HCID 178501066, compound

HRID 643448Notes

Reaction equation

HRID 643448 reaction equation
[NH:1]1[CH:5]=[N:4][CH:3]=[N:2]1.O=P(Cl)(Cl)Cl.[I:11][C:12]1[N:13]=[C:14]([C@H:22]2[CH2:27][CH2:26][C@H:25]([C:28]([O:30][CH3:31])=[O:29])[CH2:24][CH2:23]2)[N:15]2[C:20]=1C(=O)NC=N2>N1C=CC=CC=1>[NH2:1][C:5]1[C:20]2=[C:12]([I:11])[N:13]=[C:14]([C@H:22]3[CH2:23][CH2:24][C@H:25]([C:28]([O:30][CH3:31])=[O:29])[CH2:26][CH2:27]3)[N:15]2[N:2]=[CH:3][N:4]=1

Participants

5

Reactant 3

HCID 92571H-1,2,4-TriazoleHCID 24813Phosphorus oxychlorideHCID 178501067HCID 178501067, compound

Product 1

HCID 178501066HCID 178501066, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent2×

Procedure

A solution of 1H-1,2,4-triazole (0.881 g, 0.0128 mol) in pyridine (3.00 mL) was charged with POCl3 (0.396 mL, 0.00425 mol) and stirred at rt for 15 min. To this mixture was drop wise added methyl trans-4-(5-iodo-4-oxo-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-7-yl)cyclohexanecarboxylate (0.570 g, 0.01042 mol) in pyridine (6.00 mL) and stirred at rt for an additional 2.45 h. The reaction was quenched with excess 2 M of NH3 in i-PrOH (40.00 mL) at 0° C. and allowed to stir at rt for an additional 3 h. The reaction was concentrated in vacuo and partitioned between EtOAc and sat. NaHCO3 and separated. The aqueous was washed with EtOAc (3×) and the combined organic fractions were washed with brine (1×). The aqueous was re-extracted with CHCl3 (3×) and the organic was added to the EtOAc fractions. The combined organic fractions were dried over Na2SO4, filtered and concentrated in vacuo. The crude brown/red solid was purified by chromatography over silica gel [eluting with 5% MeOH in CHCl3]resulting in 438 mg, (76% yield) of the title compound as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.39-1.54 (m, 2H), 1.55-1.71 (m, 2H), 1.92-2.07 (m, 411), 2.35-2.46 (m, 1H), 3.06-3.19 (m, 1H), 3.61 (s, 3H), 6.77 (br. s., 1H) 7.86 (s, 1H) and 8.44 (br. s., 1H); MS (ES+): m/z 401.85 [MH+].

Workup

  1. stirringstirred at rt for an additional 2.45 h
  2. customThe reaction was quenched with excess 2 M of NH3 in i-PrOH (40.00 mL) at 0° C.
  3. stirringto stir at rt for an additional 3 h
  4. concentrationThe reaction was concentrated in vacuo
  5. custompartitioned between EtOAc and sat. NaHCO3
  6. customseparated
  7. washThe aqueous was washed with EtOAc (3×)
  8. washthe combined organic fractions were washed with brine (1×)
  9. extractionThe aqueous was re-extracted with CHCl3 (3×)
  10. additionthe organic was added to the EtOAc fractions
  11. dry with materialThe combined organic fractions were dried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customThe crude brown/red solid was purified by chromatography over silica gel [eluting with 5% MeOH in CHCl3]

Sources & evidence

ORD record
ord-4d4da5d9e3a44145b6c0ac90e9133421
Source dataset
uspto-grants-2010_04
Patent number
US07700594B2

Reaction notes

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