Tetrahydrofuran → HCID 178457890, compound

HRID 264025Notes

Reaction equation

HRID 264025 reaction equation
[NH2:1][CH:2]1[C:8](=[O:9])[N:7]([CH2:10][C:11]([N:13]([CH:20]([CH3:22])[CH3:21])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:12])[C:6]2[CH:23]=[CH:24][CH:25]=[CH:26][C:5]=2[N:4]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:3]1=[O:33].Cl.[N:35]1[NH:36][N:37]=[N:38][C:39]=1[C:40]1[CH:41]=[C:42]([NH2:46])[CH:43]=[CH:44][CH:45]=1.[O:47]1CCC[CH2:48]1>>[O:9]=[C:8]1[N:7]([CH2:10][C:11]([N:13]([CH:20]([CH3:22])[CH3:21])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:12])[C:6]2[CH:23]=[CH:24][CH:25]=[CH:26][C:5]=2[N:4]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:3](=[O:33])[CH:2]1[NH:1][C:48]([NH:46][C:42]1[CH:43]=[CH:44][CH:45]=[C:40]([C:39]2[NH:35][N:36]=[N:37][N:38]=2)[CH:41]=1)=[O:47]

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 101142752-(3-amino-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-phenyl-acetamideHCID 212019913-(2H-tetrazol-5-yl)-phenylamine hydrochloride

Product 1

HCID 178457890HCID 178457890, compound

Procedure

To a vigorously stirring solution of 2-(3-amino-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-phenyl-acetamide (0.070 g) in tetrahydrofuran (3 ml) at ambient temperature was added 1,1-carbonyldiimidazole (0.025 g) in one portion. The resulting was stirred for 90 minutes at ambient temperature. 3-(2H-tetrazol-5-yl)-phenylamine hydrochloride (31.3 mg), was added in one portion and the reaction mixture was heated to reflux overnight. The reaction mixture was filtered and the filtrate concentrated to a yellow oil. The oil was purified by preparative RP-HPLC on a C-18 column with a gradient elution of 43-53% 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 as a white powder (50 mg). 1H NMR (300 MHz, DMSO-d6): d 0.96(d, J=7.3 Hz, 3H), 0.98(d, J=7.3 Hz, 3H), 4.20(d, J=16.8 Hz, 1H), 4.49(d, J=17.1 Hz, 1H), 4.79(m, 1H), 5.06(d, J=7.3 Hz, 1H), 6.98(m, 2H), 7.24-7.55(m, 17H), 8.17(s, 1H), 9.44(s, 1H) MS (FAB): m/z=630.2 (MH+) (calcd. for C34H31N9O4 =629.2502) TLC (CH2Cl2 /CH3OH(9:1)): Rf =0.24 RP-HPLC (Vydac C-18, 25 cm×4.6 mm; 43-53% CH3CN in H2O with 0.1% TFA buffer; 30 minutes; 1 ml/min): tf =15 min (to =3min).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureto reflux overnight
  3. filtrationThe reaction mixture was filtered
  4. concentrationthe filtrate concentrated to a yellow oil
  5. customThe oil was purified by preparative RP-HPLC on a C-18 column with a gradient elution of 43-53% acetonitrile in water with 0.1% trifluoroacetic acid buffer over a 30 minute period at a rate of 100 ml/min
  6. additionFractions containing the desired material
  7. temperaturefrozen

Sources & evidence

ORD record
ord-c0690bfebba2424ba544eda3d5659b5d
Source dataset
uspto-grants-1997_07
Patent number
US05646140

Reaction notes

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