Sodium hydride → 2-[2,4-Dioxo-5-phenyl-3-(3-phenyl-ureido)-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-phenyl-acetamide

HRID 264022Notes

Reaction equation

HRID 264022 reaction equation
[O:1]=[C:2]1[N:8]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:7]2[CH:15]=[CH:16][CH:17]=[CH:18][C:6]=2[NH:5][C:4](=[O:19])[CH:3]1[NH:20][C:21]([NH:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:22].[H-].[Na+].Br[CH2:33][C:34]([N:36]([CH:43]([CH3:45])[CH3:44])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)=[O:35]>CN(C)C=O>[O:19]=[C:4]1[N:5]([CH2:33][C:34]([N:36]([CH:43]([CH3:45])[CH3:44])[C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[O:35])[C:6]2[CH:18]=[CH:17][CH:16]=[CH:15][C:7]=2[N:8]([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:2](=[O:1])[CH:3]1[NH:20][C:21]([NH:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:22]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 10667855US10752598, Example 20HCID 152160012-bromo-N-isopropyl-N-phenyl-acetamide

Product 1

HCID 105071092-[2,4-Dioxo-5-phenyl-3-(3-phenyl-ureido)-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-phenyl-acetamideYield 45.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(2, 4-dioxo-1-phenyl-2,3,4,5-tetrahydro-1H-benzo [b][1, 4]-diazepin-3-yl)-3-phenyl urea (0.100 g.) in N,N-dimethylformamide (2 ml) cooled to 3° C., was added sodium hydride (0.0104 g; 60% suspension in mineral oil) with stirring. The mixture was stirred 20 minutes, then 2-bromo-N-isopropyl-N-phenyl acetamide (0.0656 g) was added in one portion. The resultant mixture was stirred at ambient temperature overnight. The crude reaction mixture was purified by preparative RP-HPLC with a gradient elution of 60-72% acetonitrile in water with 0.1% trifluoroacetic acid buffer over a 30 minute period at a rate of 100 ml/min. Fractions containing the desired material were combined, frozen and lyophilized to provide the title compound (0.0653 g) as a white powder. 1H NMR (300 MHz, DMSO-d6): d 0.95 (d, J=7.3 Hz, 3H), 0.98 (d, J=7.3 Hz, 3H), 4.19 (d, J=16.6 Hz, 1H), 4.48 (d, J=16.9 Hz, 1H), 4.79 (m, 1H), 5.04 (d, J=7.8 Hz, 1H), 6.87-6.92(m, 1H), 6.95(d, J=7.6 Hz, 1H), 7.18-7.57 (m, 17H), 9.14 (s, 1H); MS (FAB): m/z=562 (MH+); TLC (CH2Cl2 /CH3OH, 19:1): Rf =0.19; RP-HPLC (Vydac C-18, 25 cm×4.6 mm; 60-72% CH3CN in H2O with 0.1% TFA buffer;, 30 minutes; 1 ml/min): tf =17.5 min (t0 =2.5 min); m.p.: 230°-235° C.

Workup

  1. stirringThe mixture was stirred 20 minutes
  2. customThe crude reaction mixture
  3. customwas purified by preparative RP-HPLC with a gradient elution of 60-72% acetonitrile in water with 0.1% trifluoroacetic acid buffer over a 30 minute period at a rate of 100 ml/min
  4. additionFractions containing the desired material
  5. temperaturefrozen

Sources & evidence

ORD record
ord-7ce0d84889a5432e97a7b647b92381ab
Source dataset
uspto-grants-1997_07
Patent number
US05646140

Reaction notes

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