Triethylamine → HCID 83528554, compound

HRID 1773301Notes

Reaction equation

HRID 1773301 reaction equation
Cl[C:2]1[C:11]2[CH2:10][NH:9][CH2:8][CH2:7][C:6]=2[C:5]2[CH:12]=[CH:13][CH:14]=[CH:15][C:4]=2[N:3]=1.C(O)(C)C.O1CCCC1.C(N(CC)CC)C.ClCCl.CO>[Pd].CO>[CH2:7]1[CH2:8][NH:9][CH2:10][C:11]2[CH:2]=[N:3][C:4]3[CH:15]=[CH:14][CH:13]=[CH:12][C:5]=3[C:6]1=2

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 21226129Dichloromethane methanolHCID 22597222Tetrahydrofuran 2-propanolHCID 118699719HCID 118699719, compound

Product 1

HCID 83528554HCID 83528554, compoundYield 85.2%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A 2 L heavy-walled glass Parr vessel equipped with a magnetic stirrer and stir bar was charged under nitrogen with 5-chloro-1,2,3,4-tetrahydrobenzo[c]-2,7-naphthyridine (30.0 g, 137 mmol), 2:1 (v/v) isopropanol-tetrahydrofuran (1100 mL), triethylamine (40.0 g, 395 mmol) and 10% by weight palladium on carbon (3.0 g). The vessel was vacuum-degassed three times, releasing the vacuum with nitrogen each time, and evacuated three times, pressurizing with hydrogen each time. The hydrogen pressure was adjusted to 55 psi and the batch was stirred at ambient temperature for 16 hours. The catalyst was filtered-off through Celite (40 g) and the filter cake was rinsed with methanol (350 mL). The filtrate and rinse were concentrated to give a light yellow solid. The solid was swished with 5:1 (v/v) dichloromethane-methanol (50 mL), collected on a filter and dried to constant weight in a vacuum oven at 40° C. This first crop material was blended with additional product obtained from the filtrate after it was in turn purified by chromatography. The filtrate was concentrated in vacuo to provide a solid, which was dissolved in a little methanol and loaded onto a 10 g KP-Sil samplet. The samplet was allowed to dry before inserting it into a 100 g KP-Sil SNAP cartridge that had been pre-equilibrated with 3 CV of 10% (v/v) 5 N ammoniacal methanol-dichloromethane. The cartridge was attached to a Biotage unit and eluted with a gradient of 5 N ammoniacal methanol-dichloromethane as follows: 10% v/v (2 CV), 10-14% v/v (5 CV), 14-16% v/v (4 CV), and 16-18% v/v (4 CV). Pure fractions were pooled and concentrated under reduced pressure to obtain the product, which was thoroughly blended with the first crop material to afford the title compound as a yellow solid (21.5 g, 85% yield).

Workup

  1. customThe vessel was vacuum-degassed three times
  2. customevacuated three times
  3. stirringthe batch was stirred at ambient temperature for 16 hours
  4. washthe filter cake was rinsed with methanol (350 mL)
  5. washThe filtrate and rinse
  6. concentrationwere concentrated
  7. customto give a light yellow solid
  8. customcollected on
  9. filtrationa filter
  10. customdried to constant weight in a vacuum oven at 40° C
  11. customobtained from the filtrate after it
  12. custompurified by chromatography
  13. concentrationThe filtrate was concentrated in vacuo
  14. customto provide a solid, which
  15. customto dry
  16. washeluted with a gradient of 5 N ammoniacal methanol-dichloromethane
  17. concentrationconcentrated under reduced pressure
  18. customto obtain the product, which

Sources & evidence

ORD record
ord-8b2800f7e586407fbe54a6382bc40701
Source dataset
uspto-grants-2016_02
Patent number
US09255096B1

Reaction notes

Loading…