Triphosgene → 1-(1-tert-butylcarbonylmethyl-2-oxo-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl)-3-(3-tert-butoxycarbonyl-4-methylphenyl)urea

HRID 1979481Notes

Reaction equation

HRID 1979481 reaction equation
Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.[CH3:13][C:14]1[CH:26]=[CH:25][C:24]([NH2:27])=[CH:23][C:15]=1[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17].[C:28]([C:32]([CH2:34][N:35]1[C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][C:40]=2[N:39]([CH:46]2[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47]2)[CH2:38][CH:37]([NH2:52])[C:36]1=[O:53])=[O:33])([CH3:31])([CH3:30])[CH3:29]>O1CCCC1.C(N(CC)CC)C>[C:28]([C:32]([CH2:34][N:35]1[C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][C:40]=2[N:39]([CH:46]2[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47]2)[CH2:38][CH:37]([NH:52][C:2]([NH:27][C:24]2[CH:25]=[CH:26][C:14]([CH3:13])=[C:15]([C:16]([O:18][C:19]([CH3:22])([CH3:20])[CH3:21])=[O:17])[CH:23]=2)=[O:4])[C:36]1=[O:53])=[O:33])([CH3:31])([CH3:29])[CH3:30]

Participants

6

Reactant 3

HCID 94429TriphosgeneHCID 154908351-tert-butylcarbonylmethyl-2-oxo-3-amino-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepineHCID 21202027Tert-butyl 5-amino-2-methylbenzoate

Product 1

HCID 212018351-(1-tert-butylcarbonylmethyl-2-oxo-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl)-3-(3-tert-butoxycarbonyl-4-methylphenyl)ureaYield 235.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolvent

Procedure

Under ice-cooling, triphosgene (205 mg) was added to a solution of tert-butyl 2-methyl-5-aminobenzoate (383 mg) in anhydrous tetrahydrofuran (40 ml), triethylamine (825 μl) was added thereto five times over 15 minutes after divided into five portions. After the mixture was stirred at room temperature for 5 minutes, a solution of 1-tert-butylcarbonylmethyl-2-oxo-3-amino-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (600 mg) in anhydrous tetrahydrofuran (10 ml) was added under ice-cooling. The resultant mixture was stirred at room temperature for one hour, the reaction mixture was poured into ice-water, extracted with ethyl acetate, and the organic layer was washed with saturated brine. After dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, diisopropyl ether was added to the residue for crystallization, and collected by filtration, to thereby obtain 960 mg of the title compound (Yield: 97%).

Workup

  1. temperatureUnder ice-cooling
  2. additionwas added
  3. temperaturecooling
  4. extractionextracted with ethyl acetate
  5. washthe organic layer was washed with saturated brine
  6. dry with materialAfter dried over anhydrous sodium sulfate
  7. customthe solvent was evaporated under reduced pressure, diisopropyl ether
  8. additionwas added to the residue for crystallization
  9. filtrationcollected by filtration

Sources & evidence

ORD record
ord-aefa23a3a8ae4605bf18f15024b64618
Source dataset
uspto-grants-2001_05
Patent number
US06239131B1

Reaction notes

Loading…