Triethylamine → HCID 53241615, compound

HRID 1023599Notes

Reaction equation

HRID 1023599 reaction equation
[CH3:1][CH:2]([O:4][C:5]1[CH:6]=[C:7]([O:11][C:12]2[N:17]=[CH:16][C:15]([NH:18][C:19](=[O:23])[C@@H:20]([CH3:22])[NH2:21])=[CH:14][CH:13]=2)[CH:8]=[CH:9][CH:10]=1)[CH3:3].C(N(CC)CC)C.Cl[C:32](Cl)([O:34]C(=O)OC(Cl)(Cl)Cl)Cl>ClCCl>[CH3:22][C@H:20]1[NH:21][C:32](=[O:34])[N:18]([C:15]2[CH:16]=[N:17][C:12]([O:11][C:7]3[CH:8]=[CH:9][CH:10]=[C:5]([O:4][CH:2]([CH3:1])[CH3:3])[CH:6]=3)=[CH:13][CH:14]=2)[C:19]1=[O:23]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 67236120HCID 67236120, compound2×

Product 1

HCID 53241615HCID 53241615, compoundYield 48.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of N1-[6-({3-[(1-methylethyl)oxy]phenyl}oxy)-3-pyridinyl]-D-alaninamide (Intermediate 32, 229 mg) and triethylamine (442 mg, 4.38 mmol) in dichloromethane (20 mL) was added a solution of triphosgene (216 mg, 0.73 mmol) in dichloromethane (10 mL) dropwise at 0° C. during 5 minutes. The resulting mixture was stirred at room temperature for 2 hours. The solvent was distilled off and the residue was partitioned between dichloromethane (3 times 50 mL) and water (50 mL). The combined organic layers were washed with brine (3 times 10 mL), dried over sodium sulphate, filtered and concentrated to afford a grey solid, which was purified by silica gel chromatography (PE:EtOAc=2:1) to afford the title compound as a white solid (120 mg).

Workup

  1. distillationThe solvent was distilled off
  2. customthe residue was partitioned between dichloromethane (3 times 50 mL) and water (50 mL)
  3. washThe combined organic layers were washed with brine (3 times 10 mL)
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto afford a grey solid, which
  8. customwas purified by silica gel chromatography (PE:EtOAc=2:1)

Sources & evidence

ORD record
ord-552190deb1c746ffbebcd95b90160366
Source dataset
uspto-grants-2014_05
Patent number
US08722695B2

Reaction notes

Loading…