1,1'-Carbonyl-di-(1,2,4-triazole) → HCID 118036313, compound

HRID 1778059Notes

Reaction equation

HRID 1778059 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[CH2:44][CH2:43][CH:42]([CH3:45])[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[CH2:44][CH2:43][CH:42]([CH3:45])[C:41]4=[O:46])=[C:30]([CH:29]([O:28][CH3:27])[O:47][CH3:48])[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 118036345HCID 118036345, compound2×HCID 1180369516-Amino-4-(2-methoxyethylamino)pyridine-3-carbonitrile2×

Product 1

HCID 118036313HCID 118036313, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
0 °C

Procedure

A solution of 6-amino-4-((2-methoxyethyl)amino)nicotinonitrile (intermediate 75, 81 mg, 0.422 mmol) in anhydrous DMF (0.5 ml) was added drop wise to a mixture of di(1H-1,2,4-triazol-1-yl)methanone (77 mg, 0.422 mmol) and DMF (0.5 ml) cooled at 0° C. After stirring for 2 h at 0° C. a solution of (racemic) 1-(2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)-3-methylpyrrolidin-2-one (intermediate 331, 68 mg, 0.212 mmol) in DMF (0.5 ml) was added. The suspension was allowed to warm to room temperature, was continued to stir for 21 h and quenched by the addition of MeOH. The reaction mixture was diluted with EtOAc, phases were separated and the water phase was extracted with EtOAc. The combined organic phases were washed with water and brine, dried using Na2SO4, filtered and evaporated. The crude product was purified by silica gel column chromatography eluting with a gradient of MeOH (0-5%) in DCM. Fractions containing the product were combined, concentrated and dried to yield the title compound as a colorless residue. (UPLC-MS 3) tR 0.96 min, ESI-MS 524.4 [M+H]+.

Workup

  1. additionwas added
  2. temperatureto warm to room temperature
  3. customquenched by the addition of MeOH
  4. additionThe reaction mixture was diluted with EtOAc, phases
  5. customwere separated
  6. extractionthe water phase was extracted with EtOAc
  7. washThe combined organic phases were washed with water and brine
  8. customdried
  9. filtrationfiltered
  10. customevaporated
  11. customThe crude product was purified by silica gel column chromatography
  12. washeluting with a gradient of MeOH (0-5%) in DCM
  13. additionFractions containing the product
  14. concentrationconcentrated
  15. customdried

Sources & evidence

ORD record
ord-de0ff769fd9b4630b4b568fb13ce0969
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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