Triethylamine → HCID 178481572, compound

HRID 1490103Notes

Reaction equation

HRID 1490103 reaction equation
[CH3:1][N:2]([C:8]1[CH:9]=[C:10]([CH:12]=[CH:13][CH:14]=1)[NH2:11])[C:3]1[NH:7][N:6]=[N:5][N:4]=1.ClC(Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl.C(N(CC)CC)C.[CH2:34]1[CH2:39][CH:38]([C:40]2([NH:53][C:54](NC3C=CC=C(NC4NN=NN=4)C=3)=[O:55])[N:46]=[CH:45][C:44]3[CH:47]=[CH:48][CH:49]=[CH:50][C:43]=3[N:42]([CH3:51])[C:41]2=[O:52])[CH2:37][CH2:36][CH2:35]1>O1CCCC1>[CH2:36]1[CH2:37][CH:38]([C@@:40]2([NH:53][C:54]([NH:11][C:10]3[CH:12]=[CH:13][CH:14]=[C:8]([N:2]([CH3:1])[C:3]4[NH:7][N:6]=[N:5][N:4]=4)[CH:9]=3)=[O:55])[N:46]=[CH:45][C:44]3[CH:47]=[CH:48][CH:49]=[CH:50][C:43]=3[N:42]([CH3:51])[C:41]2=[O:52])[CH2:39][CH2:34][CH2:35]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 178481571HCID 178481571, compoundHCID 178482162HCID 178482162, compound

Product 1

HCID 178481572HCID 178481572, compoundYield 145%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a cooled (0° C.) and stirred milky solution of 3-[N-methyl-N-(tetrazol-5-yl)amino]aniline (230 mg) in anhydrous tetrahydrofuran (30 ml) was added solid triphosgene (120 mg) in one portion, under a nitrogen atmosphere. After 5 minutes of stirring, anhydrous triethylamine (505 μl) was added dropwise and the mixture was allowed to warm to 17° C. over 15 minutes. The reaction mixture was recooled to 0° C. and a solution of Intermediate 3 (225 mg) in anhydrous tetrahydrofuran (5 ml) was added dropwise via cannula over 4 minutes. After being stirred at 0° C. for 15 minutes, the mixture was allowed to warm to room temperature and stirred for a further 2 hours before a white precipitate was removed by filtration and the solvent was evaporated under reduced pressure. The remaining residue was partitioned between ethyl acetate (200 ml) and 10% aqueous citric acid (2×40 ml) and the organic phase was then washed with brine (1×40 ml), dried (Na2SO4) and concentrated to a yellow solid. Flash chromatography (silica gel, dichloromethane-methanol, 90:10) afforded the title compound (336 mg) as a solid; mp 222°-225° C. (methanol; decomposition); [α]D23 +15.9° (c=0.71, dimethylformamide); the spectroscopic properties (1H-NMR and MS spectra) of this material were identical to those described for its racemate (Example 3). (Found: C, 61.92; H, 5.87; N, 25.96. C25 H29N9O2 requires: C, 61.59; H, 6.00; N, 25.86%).

Workup

  1. temperatureto warm to 17° C. over 15 minutes
  2. customwas recooled to 0° C.
  3. stirringAfter being stirred at 0° C. for 15 minutes
  4. temperatureto warm to room temperature
  5. stirringstirred for a further 2 hours before a white precipitate
  6. customwas removed by filtration
  7. customthe solvent was evaporated under reduced pressure
  8. customThe remaining residue was partitioned between ethyl acetate (200 ml) and 10% aqueous citric acid (2×40 ml)
  9. washthe organic phase was then washed with brine (1×40 ml)
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated to a yellow solid

Sources & evidence

ORD record
ord-3d44f5b2a4174db590ebf8de7d77b099
Source dataset
uspto-grants-1997_10
Patent number
US05681833

Reaction notes

Loading…