Triethylamine → HCID 53241716, compound

HRID 1023601Notes

Reaction equation

HRID 1023601 reaction equation
[CH3:1][C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][C:3]=1[O:9][C:10]1[N:15]=[CH:14][C:13]([NH:16][C:17](=[O:21])[C@@H:18]([CH3:20])[NH2:19])=[CH:12][CH:11]=1.C(N(CC)CC)C.Cl[C:30](Cl)([O:32]C(=O)OC(Cl)(Cl)Cl)Cl.C([O-])(O)=O.[Na+]>ClCCl>[CH3:1][C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][C:3]=1[O:9][C:10]1[N:15]=[CH:14][C:13]([N:16]2[C:17](=[O:21])[C@@H:18]([CH3:20])[NH:19][C:30]2=[O:32])=[CH:12][CH:11]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 516892Sodium BicarbonateHCID 67235654HCID 67235654, compound2×

Product 1

HCID 53241716HCID 53241716, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

N1-{6-[(2,3-dimethylphenyl)oxy]-3-pyridinyl}-D-alaninamide (Intermediate 40, 13 mg) was dissolved in dry dichloromethane (2 mL). The reaction mixture (under argon) was cooled down in an ice bath. Triethylamine (38.1 μl, 0.273 mmol) was added. Then a solution of triphosgene in dry dichloromethane (5.41 mg, 0.018 mmol, 0.40 equiv dissolved in 1 mL of DCM) was added dropwise. The reaction mixture was stirred at 0° C., under argon, during 10 min. A saturated aqueous solution of NaHCO3 was added (3 mL) and the aqueous layer was extracted with dichloromethane 4 times (4×4 mL). After drying over sodium sulphate, the solvents were removed under vacuum. The residue was purified by silica gel chromatography (Companion system, 4 g silica cartridge,) with a gradient cyclohexane/ethylacetate from 100:0 to 55:45 during 10 min and 55:45 during 20 min. This afforded the title compound (9 mg)

Workup

  1. temperatureThe reaction mixture (under argon) was cooled down in an ice bath
  2. extractionthe aqueous layer was extracted with dichloromethane 4 times (4×4 mL)
  3. dry with materialAfter drying over sodium sulphate
  4. customthe solvents were removed under vacuum
  5. customThe residue was purified by silica gel chromatography (Companion system, 4 g silica cartridge,) with a gradient cyclohexane/ethylacetate from 100:0 to 55:45 during 10 min
  6. wait55:45 during 20 min

Sources & evidence

ORD record
ord-fcdca1d19a654b2895440e0edb526b86
Source dataset
uspto-grants-2014_05
Patent number
US08722695B2

Reaction notes

Loading…