Triethylamine → N-[3(R,S)-5-Cyclohexyl-2,3-dihydro-1-methyl-2--oxo-1H-1,4-benzodiazepin-3-yl]N'-[3-(2-methyltetrazol-5-yl)phenyl]urea

HRID 2379348Notes

Reaction equation

HRID 2379348 reaction equation
C1([C:7]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[N:11]([CH3:18])[C:10](=[O:19])[CH:9]([NH:20][C:21]([O:23]C3C=CC([N+]([O-])=O)=CC=3)=O)[N:8]=2)CCCCC1.C(N([CH2:38][CH3:39])CC)C.[NH2:40][C:41]1[CH:42]=[C:43]([C:47]2[N:48]=[N:49][N:50]([CH3:52])[N:51]=2)[CH:44]=[CH:45][CH:46]=1>CN(C)C=O>[CH2:39]1[CH2:38][CH:7]([C:9]2([NH:20][C:21]([NH:40][C:41]3[CH:46]=[CH:45][CH:44]=[C:43]([C:47]4[N:48]=[N:49][N:50]([CH3:52])[N:51]=4)[CH:42]=3)=[O:23])[N:8]=[CH:7][C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[N:11]([CH3:18])[C:10]2=[O:19])[CH2:13][CH2:12][CH2:17]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 144421273-(2-Methyl-2H-tetrazol-5-yl)anilineHCID 21480451HCID 21480451, compound

Product 1

HCID 57011131N-[3(R,S)-5-Cyclohexyl-2,3-dihydro-1-methyl-2--oxo-1H-1,4-benzodiazepin-3-yl]N'-[3-(2-methyltetrazol-5-yl)phenyl]ureaYield 80.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
50 °C

Procedure

To a stirred solution of 5-cyclohexyl-1,3-dihydro-1-methyl-3(R,S)-[(4-nitrophenyloxycarbonyl)amino]-2H-1,4-benzodiazepin-2-one (150 mg, 0.34 mmol) [Example 11, Step 3], in anhydrous dimethylformamide (3 ml) was added triethylamine (48 μl, 0.34 mmol). After 5 min a solution of 5-(3-aminophenyl)-2methyltetrazole (65 mg, 0.37 mmol) in anhydrous dimethylformamide (3m]) was added, and the solution heated at 50° C. for 2 h. After this time the solution was cooled to ambient temperature and evaporated in vacuo. The residue was dissolved in ethyl acetate (5 ml) and on standing a solid precipitated. This was recrystallised from ethyl acetate to afford the urea (65 mg, 40%) as a colourless solid. mp 195°-196° C. 1H NMR (360 MHz, CDCl3) δ 1.05-2.06 (10H, m), 2.79 (1H, m), 3.45 (3H, s), 4.36 (3H, s), 5.42 (1H, d, J=8 Hz), 6.75 (1H, d, J=8 Hz), 7.15-7.60 (7H, m), 7.77 (1H, d, J=8 Hz), 8.06 (1H, s).

Workup

  1. temperatureAfter this time the solution was cooled to ambient temperature
  2. customevaporated in vacuo
  3. dissolutionThe residue was dissolved in ethyl acetate (5 ml)
  4. customprecipitated
  5. customThis was recrystallised from ethyl acetate

Sources & evidence

ORD record
ord-4519e37285ad4b188a5a1a8437f4951b
Source dataset
uspto-grants-1994_11
Patent number
US05360802

Reaction notes

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