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

HRID 743712Notes

Reaction equation

HRID 743712 reaction equation
C1([C:8]2[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[N:12]([CH3:19])[C:11](=[O:20])[CH:10]([NH:21][C:22]([O:24]C3C=CC([N+]([O-])=O)=CC=3)=O)[N:9]=2)CCCCCC1.C(N([CH2:39][CH3:40])CC)C.[NH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[C:44]([N:48]2[CH2:53][CH2:52][N:51]([CH3:54])[CH2:50][CH2:49]2)[CH:43]=1>CN(C)C=O>[CH2:40]1[CH2:39][CH2:17][CH:18]([C:10]2([NH:21][C:22]([NH:41][C:42]3[CH:47]=[CH:46][CH:45]=[C:44]([N:48]4[CH2:49][CH2:50][N:51]([CH3:54])[CH2:52][CH2:53]4)[CH:43]=3)=[O:24])[N:9]=[CH:8][C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[N:12]([CH3:19])[C:11]2=[O:20])[CH2:13][CH2:14][CH2:8]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 115646133-(4-Methylpiperazin-1-yl)anilineHCID 194246105-Cycloheptyl-1,3-dihydro-1-methyl-3(R,S)-[(4-nitrophenyloxycarbonyl)amino]-2H-1,4-benzodiazepin-2-one

Product 1

HCID 131719557N-[3(R,S)-5-Cycloheptyl-2,3-dihydro-1-methyl-2-oxo-1H-1,4-benzodiazepin-3-yl]N'-[3-(N-methyl-N'-piperazinyl)phenyl]urea

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
50 °C

Procedure

To a stirred solution of 5-cycloheptyl-1,3-dihydro-1-methyl-3(R,S)-[(4-nitrophenyloxycarbonyl)amino]-2H-1,4-benzodiazepin-2-one (200 mg) in anhydrous dimethylformamide (5 ml), under an atmosphere of nitrogen, was added triethylamine (61 μl). After 2 min a solution of 1-amino-3-(N-methyl-N'-piperazinyl)benzene (85 mg) in anhydrous dimethylformamide (5 ml) was added and the solution heated at 50° C. for 1.5 h. After this time the solvent was evaporated in vacuo and the residue partitioned between ethyl acetate (20 ml) and water (20 ml). An undissolved solid was filtered off and triturated with anhydrous diethyl ether to give the desired urea (128 mg) as a white solid. 1H NMR (360 MHz, D6 -DMSO) δ 1.13-1.94 (12H, m), 2.19 (3H, s), 2.40-2.43 (4H, m), 3.03-3.12 (5H, m), 3.30 (3H, s), 5.04 (1H, d, J=8.4 Hz), 6.49 (1H, dd, 8.1 and 1 Hz), 6.62 (1H, d, J=9.0 Hz), 7.03 (1H, t, J=8.1 Hz), 7.12 (1H, m), 7.22 (1H, d, J=8.4 Hz), 7.38 (1H, dd, J=7.6 and 7.6 Hz), 7.54 (1H, d, J=7.7 Hz), 7.63 (1H, dd, J=8.3 and 8.3 Hz), 7.76 (1H, d, J=7.6 Hz), 8.86 (1H, s). MS (CI, NH3) 502 (M+).

Workup

  1. customAfter this time the solvent was evaporated in vacuo
  2. customthe residue partitioned between ethyl acetate (20 ml) and water (20 ml)
  3. filtrationAn undissolved solid was filtered off
  4. customtriturated with anhydrous diethyl ether

Sources & evidence

ORD record
ord-7c4998ecaf564c68a8fc224c68ab9619
Source dataset
uspto-grants-1996_09
Patent number
US05556969

Reaction notes

Loading…