1,1'-Carbonyldiimidazole → HCID 178447221, compound

HRID 482349Notes

Reaction equation

HRID 482349 reaction equation
[C:1]([N:8]1[CH:12]=[CH:11]N=C1)(N1C=CN=C1)=[O:2].[NH2:13][CH:14]1[C:20](=[O:21])[N:19]([CH2:22][C:23]([N:25](C(C)C)[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:24])[C:18]2[CH:35]=[CH:36][CH:37]=[CH:38][C:17]=2[C:16](C2C=CC=CC=2)=[N:15]1.Cl.[N:46]1[NH:47][N:48]=[N:49][C:50]=1[C:51]1[CH:52]=C(N)C=[CH:55][CH:56]=1>C1COCC1>[CH:26]([CH:22]([N:19]1[C:18]2[CH:17]=[CH:38][CH:37]=[CH:36][C:35]=2[C:16]([C:17]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:18]=2)=[N:15][CH:14]([NH:13][C:1]([NH:8][C:12]2[CH:11]=[CH:55][CH:56]=[C:51]([C:50]3[NH:46][N:47]=[N:48][N:49]=3)[CH:52]=2)=[O:2])[C:20]1=[O:21])[C:23]([NH:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:24])([CH3:31])[CH3:27]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 190636702-(3-Amino-2-oxo-5-phenyl-2,3-dihydro-benzo[e][1,4]diazepin-1-yl)-N-isopropyl-N-phenyl-acetamideHCID 212019913-(2H-tetrazol-5-yl)-phenylamine hydrochloride

Product 1

HCID 178447221HCID 178447221, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

According to Process B, a mixture of of 1,1'-carbonyldiimidazole (28.6 mg, 0.176 mmol) and 2-(3-Amino-2-oxo-5-phenyl-2,3-dihydro-benzo[e][1,4]diazepin-1-yl)-N-isopropyl-N-phenyl-acetamide (75.0 mg, 0.176 mmol), prepared as in Intermediate 13, in anhydrous THF (5 mL) is stirred at ambient temperature under a nitrogen atmosphere for approximately 30 min. and then heated to reflux. After refluxing for 2 hrs, 3-(2H-tetrazol-5-yl)-phenylamine hydrochloride (36.5 mg, 0.185 mmol), prepared as in Intermediate 17, is added in one portion and the reaction is held at reflux for an additional 5 hrs and then concentrated in vacuo to a residue. The residue is purified by reversed-phase HPLC on a C-18 column with a gradient elution of 30-68% acetonitrile in aqueous trifluoroacetic acid (0.1% v/v) over 30 min. at 100 mL/min. Fractions containing the product are combined, frozen, and lyophilized to provide the title compound as a white lyophile (37 mg, 0.060 mmol). 1H NMR (300 MHz, d6-DMSO) δ=1.04 (d, 6H); 4.21 (d, J=16.4 Hz, 1H); 4.31 (d, J=17.1 Hz, 1H); 4.79-6.86 (m, 1H); 5.35-5.36 (m, 1H); 7.32-7.78 (m, 19H); 8.26 (b, 1H); 9.38 (b, 1H); MS (ESI): [M+H]+ =614.

Workup

  1. additiona mixture
  2. temperatureheated to reflux
  3. temperatureAfter refluxing for 2 hrs
  4. additionis added in one portion
  5. temperatureat reflux for an additional 5 hrs
  6. concentrationconcentrated in vacuo to a residue
  7. customThe residue is purified by reversed-phase HPLC on a C-18 column with a gradient elution of 30-68% acetonitrile in aqueous trifluoroacetic acid (0.1% v/v) over 30 min. at 100 mL/min
  8. additionFractions containing the product
  9. temperaturefrozen

Sources & evidence

ORD record
ord-09d0a1908a5044d6a2ebd9a099e4d962
Source dataset
uspto-grants-1998_08
Patent number
US05795887

Reaction notes

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