Terephthaloyl chloride → tert-butyl N-[(3S)-5-[4-[(3S)-3-(tert-butoxycarbonylamino)-2-oxo-3,4-dihydro-1H-1,5-benzodiazepine-5-carbonyl]benzoyl]-2-oxo-3,4-dihydro-1H-1,5-benzodiazepin-3-yl]carbamate

HRID 1481937Notes

Reaction equation

HRID 1481937 reaction equation
[C:1]([O:5][C:6](=[O:20])[NH:7][C@@H:8]1[C:14](=[O:15])[NH:13][C:12]2[CH:16]=[CH:17][CH:18]=[CH:19][C:11]=2[NH:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].C([N:23]([CH2:26][CH3:27])[CH2:24][CH3:25])C.[C:28](Cl)(=[O:38])[C:29]1[CH:37]=[CH:36][C:32]([C:33](Cl)=[O:34])=[CH:31][CH:30]=1>C1COCC1>[C:1]([O:5][C:6]([NH:7][C@@H:8]1[C:14](=[O:15])[NH:13][C:12]2[CH:16]=[CH:17][CH:18]=[CH:19][C:11]=2[N:10]([C:28]([C:29]2[CH:37]=[CH:36][C:32]([C:33]([N:23]3[C:24]4[CH:25]=[CH:18][CH:19]=[CH:11][C:12]=4[NH:13][C:14](=[O:15])[C@@H:27]([NH:7][C:6](=[O:20])[O:5][C:1]([CH3:3])([CH3:2])[CH3:4])[CH2:26]3)=[O:34])=[CH:31][CH:30]=2)=[O:38])[CH2:9]1)=[O:20])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 7488Terephthaloyl chlorideHCID 8471TriethylamineHCID 22881971tert-butyl N-[(3S)-2-oxo-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-3-yl]carbamate2×

Product 1

HCID 90220967tert-butyl N-[(3S)-5-[4-[(3S)-3-(tert-butoxycarbonylamino)-2-oxo-3,4-dihydro-1H-1,5-benzodiazepine-5-carbonyl]benzoyl]-2-oxo-3,4-dihydro-1H-1,5-benzodiazepin-3-yl]carbamateYield 39%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To ((S)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl)-carbamic acid tert-butyl ester (Intermediate 2) (57.9 mg, 0.209 mmol) and triethylamine (29.1 μL, 0.209 mmol) in anhydrous THF (1 mL) was added terephthaloyl dichloride (21.2 mg, 0.104 mmol). The resulting suspension was stirred at room temperature for 4 h. The mixture was concentrated and the residue was triturated with water. The solid was collected, washed with water and purified by silica gel chromatography to provide tert-butyl N-[(3S)-5-[4-[(3S)-3-(tert-butoxycarbonylamino)-2-oxo-3,4-dihydro-1H-1,5-benzodiazepine-5-carbonyl]benzoyl]-2-oxo-3,4-dihydro-1H-1,5-benzodiazepin-3-yl]carbamate as a white solid (27.6 mg, 39%).

Workup

  1. concentrationThe mixture was concentrated
  2. customthe residue was triturated with water
  3. customThe solid was collected
  4. washwashed with water
  5. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-491a33b783d84fa9a97ab778b2b50ccd
Source dataset
uspto-grants-2016_08
Patent number
US09409888B2

Reaction notes

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