1,2-Dichloroethane → 2-[1-(Isopropyl-phenyl-carbamoylmethyl)-3-methyl-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-3-yl]acetamide

HRID 343199

Reaktionsgleichung

Reaktionsgleichung von HRID 343199
[CH:1]([C:4]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)([C:29](=[O:31])[NH2:30])N1C(=O)C(CC(O)=O)(C)C(=O)N(C2C=CC=CC=2)C2C=CC=CC1=2)([CH3:3])[CH3:2].C(O[C:46]([CH2:48][C:49]1([CH2:83]C(O)=O)[C:55](=[O:56])[N:54](C(C(C)C)(C2C=CC(OC)=CC=2)C(=O)N)[C:53]2[CH:72]=[CH:73][CH:74]=[CH:75][C:52]=2[N:51]([C:76]2[CH:81]=[CH:80][CH:79]=[CH:78][CH:77]=2)[C:50]1=[O:82])=[O:47])C1C=CC=CC=1.C(Cl)CCl.C1C=CC2N(O)N=[N:97]C=2C=1.[OH-].[NH4+]>CN(C=O)C.CCOC(C)=O>[CH:1]([C:4]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)([C:29](=[O:31])[NH2:30])[N:51]1[C:50](=[O:82])[C:49]([CH2:48][C:46]([NH2:97])=[O:47])([CH3:83])[C:55](=[O:56])[N:54]([C:53]2[CH:52]=[CH:75][CH:74]=[CH:73][CH:72]=2)[C:81]2[CH:80]=[CH:79][CH:78]=[CH:77][C:76]1=2)([CH3:3])[CH3:2]

Komponenten

8

Edukt 5

HCID 111,2-DichloroethaneHCID 14923Ammonium HydroxideHCID 757711-HydroxybenzotriazoleHCID 67696769[1-(isopropyl-phenyl-carbamoylmethyl)-3-methyl-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl]acetic acidHCID 86753587{3-(Benzyloxycarbonyl-methyl)-1-[isopropyl-(4-methoxy-phenyl)-carbamoylmethyl]-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl}acetic acid

Produkt 1

HCID 677006232-[1-(Isopropyl-phenyl-carbamoylmethyl)-3-methyl-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-3-yl]acetamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a stirring solution of 233 mg (0.47 mmol) of [1-(Isopropyl-phenyl-carbamoylmethyl)-3-methyl-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl]-acetic acid, prepared as in Intermediate 7, in 2 mL DMF is added 98 mg (0.51 mmol, 1.1 equiv) of EDC and 76 mg (0.56 mmol, 1.2 equiv) of HOBT. The resulting solution is stirred 5 min, then 75 mL (0.61 mmol, 1.3 equiv) of a 30% solution of ammonium hydroxide is added. The solution is stirred 2 h at RT, then poured into 30 mL of EtOAc and extracted H2O (1×30 mL) and NaHCO3 (1×30 mL). The organic layer is separated, dried (MgSO4), and the solvent removed in vacuo. Purification of the resulting grey solid via reverse phase MPLC using a C-18 column and 60% acetonitrile/40% H2O with 0.1% TFA as eluent followed by lyophilization afforded 35 mg of the title compound as a white amorphous solid: 1H NMR (CDCl3, 300 MHz, mixture of conformers) δ7.47-6.80 (m, 14H), 6.70 (s, br, 0.5H), 5.84 (s, br, 0.5H), 5.03 (m, 1H), 4.63 (d, 0.5H, J=16.6), 4.35 (d, 0.5H, J=16.3), 4.08 (d, 0.5H, J=16.6), 3.74 (d, 0.5H, J=16.3), 3.10 (m, 1H), 2.46 (d, 0.5H, J=14.7), 2.23 (d, 0.5H, J=14.7), 1.65 (s, 1.5H), 1.16 (m, 7.5H); low resolution MS (FAB)m/e 499 (MH+).

Aufarbeitung

  1. stirringThe solution is stirred 2 h at RT
  2. extractionextracted H2O (1×30 mL) and NaHCO3 (1×30 mL)
  3. customThe organic layer is separated
  4. dry with materialdried (MgSO4)
  5. customthe solvent removed in vacuo
  6. customPurification of the resulting grey solid via reverse phase MPLC

Quellen und Nachweise

ORD-Eintrag
ord-7e94392d699b43ec8ebbfd0d678920e6
Quelldatensatz
uspto-grants-1999_01
Patentnummer
US05859007

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