Triethylamine → HCID 70199112, compound

HRID 1956697Notes

Reaction equation

HRID 1956697 reaction equation
[C:1]([C:3]1[CH:33]=[CH:32][C:6]([CH2:7][N:8]2[C:12]([CH2:13][NH:14][C@@H:15]([CH2:26][CH2:27][S:28]([CH3:31])(=[O:30])=[O:29])[CH2:16][NH:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[CH:20]=3)=[CH:11][N:10]=[CH:9]2)=[CH:5][CH:4]=1)#[N:2].C(N(CC)CC)C.Cl[C:42](Cl)([O:44]C(=O)OC(Cl)(Cl)Cl)Cl.Cl.CCOCC>C1COCC1.C(Cl)Cl.CCOC(C)=O>[ClH:25].[Cl:25][C:21]1[CH:20]=[C:19]([CH:24]=[CH:23][CH:22]=1)[CH2:18][N:17]1[CH2:16][C@H:15]([CH2:26][CH2:27][S:28]([CH3:31])(=[O:30])=[O:29])[N:14]([CH2:13][C:12]2[N:8]([CH2:7][C:6]3[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:33][CH:32]=3)[CH:9]=[N:10][CH:11]=2)[C:42]1=[O:44]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 10953452Ether hydrochlorideHCID 67642996HCID 67642996, compound

Product 1

HCID 70199112HCID 70199112, compoundYield 19.9%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of the product from Step G (63 mg, 0.17 mmol) in 2.5 mL of THF at 0° C. was added triethylamine (0.15 mL, 1.0 mmol), followed by triphosgene (31 mg, 0.10 mmol). The reaction was stirred at 0° C. for 1.5 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 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 (9.3 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. custompurified with a mixed gradient of 25%-55% acetonitrile/0.1% TFA
  6. wait75%-45% 0.1% aqueous TFA over 50 minutes
  7. concentrationAfter concentration in vacuo
  8. customthe resultant product was partitioned between dichloromethane and aq. NaHCO3 soln
  9. extraction, and the aqueous phase was extracted with CH2Cl2
  10. washThe organic solution was washed with brine
  11. dry with materialdried (Na2SO4)
  12. filtrationfiltered
  13. concentrationconcentrated to dryness
  14. customto provide the product free base, which
  15. concentrationAfter concentrated in vacuo

Sources & evidence

ORD record
ord-bcba43788ce7499faae1927deeb2ded2
Source dataset
uspto-grants-1998_07
Patent number
US05780492

Reaction notes

Loading…