1,1'-Carbonyl-di-(1,2,4-triazole) → HCID 118036529, compound

HRID 1778008Notes

Reaction equation

HRID 1778008 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:48][CH3:49])[C:30]1[C:39]([CH2:40][N:41]2[CH2:46][CH2:45][S:44][CH2:43][C:42]2=[O:47])=[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]([CH2:40][N:41]4[CH2:46][CH2:45][S:44][CH2:43][C:42]4=[O:47])=[C:30]([CH:29]([O:48][CH3:49])[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 118037033HCID 118037033, compound2×

Product 1

HCID 118036529HCID 118036529, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
0 °C

Procedure

A solution of 6-amino-4-((2-methoxyethyl)amino)nicotinonitrile (intermediate 75, 478 mg, 2.46 mmol) in anhydrous DMF (4 ml) was added drop wise to a mixture of di(1H-1,2,4-triazol-1-yl)methanone (449 mg, 2.46 mmol) and DMF (4 ml) cooled at 0° C. After stirring for 60 minutes 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)methyl)thiomorpholin-3-one (intermediate 208, 415 mg, 1.230 mmol) in DMF (4 ml) was added. The reaction mixture was stirred for approximately 24 h at room temperature, quenched by the addition of MeOH. The residue was diluted with EtOAc and water, filtered to remove insoluble byproducts. Phases were separated and the aqueous layer was washed with EtOAc (2×). The organic layers were combined, washed with water, dried using Na2SO4, filtered and evaporated. The crude product was purified using silica gel column chromatography eluting with a gradient of MeOH (0-3%) in DCM, followed by an additional purification with a gradient of MeOH (0-2%) in DCM. Fractions containing the product were combined and evaporated to yield the title compound as a white solid. (UPLC-MS 3) tR 0.98 min, ESI-MS 556.4 [M+H]+. 1H NMR (600 MHz, CDCl3) δ 13.77 (s, 1H), 8.17 (s, 1H), 7.48 (s, 1H), 7.45 (s, 1H), 5.52-5.37 (m, 1H), 4.82 (s, 2H), 3.98-3.93 (m, 2H), 3.59-3.55 (m, 2H), 3.55-3.50 (m, 2H), 3.47-3.39 (m, 8H), 3.36-3.30 (m, 5H), 2.77 (t, 2H), 2.74-2.70 (m, 2H), 1.96-1.89 (m, 2H).

Workup

  1. temperatureto warm to room temperature
  2. stirringThe reaction mixture was stirred for approximately 24 h at room temperature
  3. customquenched by the addition of MeOH
  4. additionThe residue was diluted with EtOAc and water
  5. filtrationfiltered
  6. customto remove insoluble byproducts
  7. customPhases were separated
  8. washthe aqueous layer was washed with EtOAc (2×)
  9. washwashed with water
  10. customdried
  11. filtrationfiltered
  12. customevaporated
  13. customThe crude product was purified
  14. washeluting with a gradient of MeOH (0-3%) in DCM
  15. customfollowed by an additional purification with a gradient of MeOH (0-2%) in DCM
  16. additionFractions containing the product
  17. customevaporated

Sources & evidence

ORD record
ord-ac3c690052544a25aa731622ddebdc7c
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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