Triethylamine → HCID 18663369, compound

HRID 1956691Notes

Reaction equation

HRID 1956691 reaction equation
[C:1]([C:3]1[CH:26]=[CH:25][C:6]([CH2:7][N:8]2[C:12]([CH2:13][NH:14][CH2:15][CH2:16][NH:17][C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([Cl:24])[CH:19]=3)=[CH:11][N:10]=[CH:9]2)=[CH:5][CH:4]=1)#[N:2].C(N(CC)CC)C.Cl[C:35](Cl)([O:37]C(=O)OC(Cl)(Cl)Cl)Cl.Cl.CCOCC>C1COCC1.C(Cl)Cl.CCOC(C)=O>[ClH:24].[Cl:24][C:20]1[CH:19]=[C:18]([N:17]2[CH2:16][CH2:15][N:14]([CH2:13][C:12]3[N:8]([CH2:7][C:6]4[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:26][CH:25]=4)[CH:9]=[N:10][CH:11]=3)[C:35]2=[O:37])[CH:23]=[CH:22][CH:21]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 10953452Ether hydrochlorideHCID 19611597HCID 19611597, compound

Product 1

HCID 18663369HCID 18663369, compoundYield 19.5%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of the product from Step B (500 mg, 1.37 mmol) in 9.6 mL of THF at 0° C. was added triethylamine (1.2 mL, 8.6 mmol), followed by triphosgene (251 mg, 0.847 mmol). The reaction was stirred at 0° C. for one hour, then poured into EtOAc and washed with sat. aq. NaHCO3 and brine. The solution was dried (Na2SO4), filtered, and concentrated in vacuo. The product was purified by silica gel chromatography (2.5-5% MeOH/CH2Cl2), then taken up in methanol and injected onto a preparative HPLC column and purified with a mixed gradient of 25%-55% acetonitrile/0.1% TFA; 75%-45% 0.1% aqueous TFA over 50 minutes. After concentration in vacuo, the resultant product was partitioned between dichloromethane and aq. NaHCO3 soln., and the aqueous phase was extracted with CH2Cl2. The organic solution was washed with brine, dried (Na2SO4), filtered, and concentrated to dryness to provide the product free base, which was taken up in CH2Cl2 and treated with excess 1M HCl/ether solution. After concentrated in vacuo, the titled product (57.3 mg) was isolated as a white powder.

Workup

  1. washwashed with sat. aq. NaHCO3 and brine
  2. dry with materialThe solution was dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe product was purified by silica gel chromatography (2.5-5% MeOH/CH2Cl2)
  6. custompurified with a mixed gradient of 25%-55% acetonitrile/0.1% TFA
  7. wait75%-45% 0.1% aqueous TFA over 50 minutes
  8. concentrationAfter concentration in vacuo
  9. customthe resultant product was partitioned between dichloromethane and aq. NaHCO3 soln
  10. extraction, and the aqueous phase was extracted with CH2Cl2
  11. washThe organic solution was washed with brine
  12. dry with materialdried (Na2SO4)
  13. filtrationfiltered
  14. concentrationconcentrated to dryness
  15. customto provide the product free base, which
  16. concentrationAfter concentrated in vacuo

Sources & evidence

ORD record
ord-58fdc0c65d644071ad9fd6de6d294d65
Source dataset
uspto-grants-1998_07
Patent number
US05780492

Reaction notes

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