1,2-Dichloroethane → HCID 54218403, compound

HRID 1601055Notes

Reaction equation

HRID 1601055 reaction equation
C(Cl)CCl.[C:5]([C:8]1[CH:9]=[CH:10][C:11]2[NH:17][CH:16]([CH2:18][C:19]([O:21][CH3:22])=[O:20])[C:15](=[O:23])[N:14]([CH:24]([CH3:26])[CH3:25])[CH2:13][C:12]=2[CH:27]=1)([OH:7])=O.Cl.Cl.[NH2:30][CH2:31][C:32]1[NH:33][C:34]2[CH:40]=[CH:39][CH:38]=[CH:37][C:35]=2[N:36]=1.C1C=CC2N(O)N=NC=2C=1.O.C(N(C(C)C)CC)(C)C>CN(C=O)C.CO.CCOC(C)=O>[CH:24]([N:14]1[CH2:13][C:12]2[CH:27]=[C:8]([C:5]([NH:30][CH2:31][C:32]3[NH:36][C:35]4[CH:37]=[CH:38][CH:39]=[CH:40][C:34]=4[N:33]=3)=[O:7])[CH:9]=[CH:10][C:11]=2[NH:17][CH:16]([CH2:18][C:19]([O:21][CH3:22])=[O:20])[C:15]1=[O:23])([CH3:26])[CH3:25]

Participants

10

Reactant 6

HCID 111,2-DichloroethaneHCID 962WaterHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2723957(1H-benzo[d]imidazol-2-yl)methanamine dihydrochlorideHCID 53904987HCID 53904987, compound

Product 1

HCID 54218403HCID 54218403, compoundYield 82%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

EDC (173 mg, 0.90 mmol) was added to a stirred solution of methyl (±)-7-carboxy-4-isopropyl-3-oxo-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine-2-acetate (240.3 mg, 0.75 mmol), 2-(aminomethyl)benzimidazole dihydrochloride (198 mg, 0.90 mmol), HOBT.H2O (122 mg, 0.90 mmol), and diisopropylethylamine (0.52 mL, 3.0 mmol) in anhydrous DMF (4 mL) at RT. After 20 h, the reaction was concentrated on the rotavap (high vacuum), and the residue was diluted with H2O (5 mL) to afford a gummy precipitate. EtOAc (3 mL) was added and the mixture was stirred briskly. The precipitate remained gummy, but changed in form so that it was suspended as a mass in the solvents. The solvents were drawn off with a pipet and the residue was suspended in MeOH (3 mL) and EtOAc (6 mL). The mixture was stirred briskly at RT for several min, then was cooled in ice and filtered. The filter pad was washed with EtOAc and dried in high vacuum to leave the title compound (275.1 mg, 82%) as an off-white powder: 1H NMR (250 MHz, 20% CD3OD/CDCl 3) δ 7.45-7.70 (m, 4H), 7.15-7.35 (m, 2H), 6.56 (d, J=9.1 Hz, 1H), 5.22 (d, J=16.9 Hz, 1H), 5.13 (app t, 1H), 4.72-4.92 (m, 1H), 4.72 (s, 2H), 4.03 (d, J=16.9 Hz, 1H), 3.74 (s, 3H), 3.00 (d, J=16.4, 7.7 Hz, 1H), 2.67 (dd, J=16.4, 6.0 Hz, 1H), 1.21 (d, J=6.7 Hz, 3H), 1.03 (d, J=6.8 Hz, 3H); MS (ES) 450.2 (M+H)+.

Workup

  1. customat RT
  2. concentrationthe reaction was concentrated on the rotavap (high vacuum)
  3. additionthe residue was diluted with H2O (5 mL)
  4. customto afford a gummy precipitate
  5. stirringThe mixture was stirred briskly at RT for several min
  6. temperaturewas cooled in ice
  7. filtrationfiltered
  8. washThe filter pad was washed with EtOAc
  9. customdried in high vacuum

Sources & evidence

ORD record
ord-294f16306b8e4164b475e746006dceb4
Source dataset
uspto-grants-1999_11
Patent number
US05977101

Reaction notes

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