1,1'-Carbonyl-di-(1,2,4-triazole) → HCID 118037015, compound

HRID 1778061Notes

Reaction equation

HRID 1778061 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:47][CH3:48])[C:30]1[C:39]([N:40]2[CH2:45][CH2:44][O:43][CH2:42][C:41]2=[O:46])=[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[CH2:45][CH2:44][O:43][CH2:42][C:41]4=[O:46])=[C:30]([CH:29]([O:47][CH3:48])[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 118036572HCID 118036572, compound2×HCID 1180369516-Amino-4-(2-methoxyethylamino)pyridine-3-carbonitrile2×

Product 1

HCID 118037015HCID 118037015, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
0 °C

Procedure

A solution of 6-amino-4-((2-methoxyethyl)amino)nicotinonitrile (intermediate 75, 683 mg, 3.56 mmol) in anhydrous DMF (6 ml) was added drop wise to a mixture of di(1H-1,2,4-triazol-1-yl)methanone (648 mg, 3.56 mmol) and DMF (6 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 4-(2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)morpholin-3-one (intermediate 333, 683 mg, 1.78 mmol) in DMF (6 ml) was added. The suspension was allowed to warm to room temperature, was continued to stir for 17 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 washed with brine, 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, 1-6%) in DCM. Fractions containing the product were combined, concentrated. The solid was precipitated from DCM and n-hexane, sonicated, filtered and dried to yield the title compound as a white solid. (UPLC-MS 3) tR 0.83 min, ESI-MS 526.2 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 13.31 (s, 1H), 8.27 (s, 1H), 7.72 (s, 1H), 7.55 (s, 1H), 6.88 (t, 1H), 5.34 (s, 1H), 4.23 (d, 2H), 4.10-3.84 (m, 4H), 3.71-3.24 (m, 15H), 2.92-2.82 (m, 2H), 1.98-1.87 (m, 2H).

Workup

  1. temperatureto warm to room temperature
  2. temperatureto warm to room temperature
  3. stirringto stir for 17 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. washThe combined organic phases were washed with brine
  13. customdried
  14. filtrationfiltered
  15. customevaporated
  16. customThe crude product was purified by silica gel column chromatography
  17. washeluting with a gradient of MeOH (containing 0.3% of aqueous NH3, 1-6%) in DCM
  18. additionFractions containing the product
  19. concentrationconcentrated
  20. customThe solid was precipitated from DCM and n-hexane
  21. customsonicated
  22. filtrationfiltered
  23. customdried

Sources & evidence

ORD record
ord-e60a272a6b264da88df435f94cdae73e
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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