1,1'-Carbonyl-di-(1,2,4-triazole) → HCID 118036869, compound

HRID 1778063Notes

Reaction equation

HRID 1778063 reaction equation
[NH2:1][C:2]1[CH:9]=[C:8]([NH:10][CH2:11][CH2:12][O:13][CH3:14])[C:5]([C:6]#[N:7])=[CH:4][N:3]=1.N1([C:20](N2C=NC=N2)=[O:21])C=NC=N1.[CH3:27][O:28][CH:29]([O:46][CH3:47])[C:30]1[C:39]([N:40]2[CH2:44][CH2:43][O:42][C:41]2=[O:45])=[CH:38][C:37]2[CH2:36][CH2:35][CH2:34][NH:33][C:32]=2[N:31]=1>CN(C=O)C>[C:6]([C:5]1[C:8]([NH:10][CH2:11][CH2:12][O:13][CH3:14])=[CH:9][C:2]([NH:1][C:20]([N:33]2[C:32]3[C:37](=[CH:38][C:39]([N:40]4[CH2:44][CH2:43][O:42][C:41]4=[O:45])=[C:30]([CH:29]([O:46][CH3:47])[O:28][CH3:27])[N:31]=3)[CH2:36][CH2:35][CH2:34]2)=[O:21])=[N:3][CH:4]=1)#[N:7]

Participants

5

Reactant 3

HCID 43939611,1'-Carbonyl-di-(1,2,4-triazole)HCID 1180369516-Amino-4-(2-methoxyethylamino)pyridine-3-carbonitrile2×HCID 118037047HCID 118037047, compound2×

Product 1

HCID 118036869HCID 118036869, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
0 °C

Procedure

A solution of 6-amino-4-((2-methoxyethyl)amino)nicotinonitrile (intermediate 75, 629 mg, 3.271 mmol) in anhydrous DMF (5 ml) was added drop wise to a mixture of di(1H-1,2,4-triazol-1-yl)methanone (596 mg, 2.86 mmol) and DMF (5 ml) cooled at 0° C. After stirring for 1 h at 0° C. the reaction mixture was allowed to warm to room temperature and a solution of 3-(2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)oxazolidin-2-one (intermediate 335, 685 mg, 1.635 mmol) in DMF (5 ml) was added. The suspension was allowed to warm to room temperature, was continued to stir for 18 h and quenched by the addition of MeOH. The reaction mixture was diluted with water, filtered to remove solid impurities and the filter cake was washed with EtOAc. The filtrate was diluted with brine and EtOAc, phases were separated and the water phase was extracted with EtOAc (2×). The combined organic phases were dried using Na2SO4, filtered and evaporated. The crude product was purified by silica gel column chromatography eluting with a gradient of MeOH (containing 0.3% of aqueous NH3, 0-4%) in DCM, followed by another purification on silica gel eluting with a mixture of MeOH (containing 0.3% of aqueous NH3)/DCM (98/2). Fractions containing the product were combined, concentrated. The solid was suspended in EtOAc, sonicated, filtered and dried to yield the title compound as a white solid. (UPLC-MS 3) tR 0.86 min, ESI-MS 512.2 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 13.30 (s, 1H), 8.27 (s, 1H), 7.78 (s, 1H), 7.54 (s, 1H), 6.88 (t, 1H), 5.49 (s, 1H), 4.47 (t, 2H), 3.98-3.87 (m, 4H), 3.53 (t, 2H), 3.43-3.28 (m, 11H), 2.85 (t, 2H), 1.96-1.86 (m, 2H).

Workup

  1. temperatureto warm to room temperature
  2. temperatureto warm to room temperature
  3. stirringto stir for 18 h
  4. customquenched by the addition of MeOH
  5. additionThe reaction mixture was diluted with water
  6. filtrationfiltered
  7. customto remove solid impurities
  8. washthe filter cake was washed with EtOAc
  9. additionThe filtrate was diluted with brine and EtOAc, phases
  10. customwere separated
  11. extractionthe water phase was extracted with EtOAc (2×)
  12. customThe combined organic phases were dried
  13. filtrationfiltered
  14. customevaporated
  15. customThe crude product was purified by silica gel column chromatography
  16. washeluting with a gradient of MeOH (containing 0.3% of aqueous NH3, 0-4%) in DCM
  17. customfollowed by another purification on silica gel eluting with a mixture of MeOH (containing 0.3% of aqueous NH3)/DCM (98/2)
  18. additionFractions containing the product
  19. concentrationconcentrated
  20. customsonicated
  21. filtrationfiltered
  22. customdried

Sources & evidence

ORD record
ord-27deeab991234871a2bc1330e5912c39
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

Loading…