1-Hydroxybenzotriazole → trans-4-(N-tert-Butoxycarbonylglycylamino)-N-tert-Butoxycarbonyl-L-Proline 4-Benzylphenylamide

HRID 2185451Notes

Reaction equation

HRID 2185451 reaction equation
ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH2:23]([C:30]1[CH:36]=[CH:35][C:33]([NH2:34])=[CH:32][CH:31]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.[C:37]([O:41][C:42]([NH:44][CH2:45][C:46]([NH:48][C@H:49]1[CH2:53][N:52]([C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[C@H:51]([C:61](O)=[O:62])[CH2:50]1)=[O:47])=[O:43])([CH3:40])([CH3:39])[CH3:38]>ClCCl.C(Cl)(Cl)Cl>[CH2:23]([C:30]1[CH:31]=[CH:32][C:33]([NH:34][C:61](=[O:62])[C@@H:51]2[CH2:50][C@@H:49]([NH:48][C:46](=[O:47])[CH2:45][NH:44][C:42]([O:41][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:43])[CH2:53][N:52]2[C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])=[CH:35][CH:36]=1)[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 136914Benzenamine, 4-(phenylmethyl)-HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 21341559trans-4-(N-tert-butoxycarbonylglycyl)amino-N-tert-butoxycarbonyl-L-proline

Product 1

HCID 131723253trans-4-(N-tert-Butoxycarbonylglycylamino)-N-tert-Butoxycarbonyl-L-Proline 4-BenzylphenylamideYield 92.3%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

1-Hydroxybenzotriazole (21 mg) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (65 mg) were added to a solution of 4-benzylaniline (57 mg) and trans-4-(N-tert-butoxycarbonylglycylamino)-N-tert-butoxycarbonyl-L-proline (Compound D103 (B), 120 mg) in dichloromethane (3 mL) at 0° C. The mixture was stirred at room temperature for 4 hr. The reaction mixture was diluted with chloroform and washed with saturated sodium hydrogen carbonate and brine. The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography (chloroform:methanol=100:1, v/v) to give the title compound (158 mg) as a colorless foam: 1H NMR (400 MHz, CDCl3) δ 1.44 (s, 18H), 2.01 (m, 1H), 2.70 (m, 1H), 3.26 (m, 1H), 3.75 (m, 3H), 3.91 (s, 2H), 4.50 (m, 2H), 5.53 (m, 1H), 6.79 (m, 1H), 7.08-7.28 (m,7H), 7.40 (d, J=7.8 Hz, 2H), and 9.28 (m, 1H).

Workup

  1. washwashed with saturated sodium hydrogen carbonate and brine
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by silica gel column chromatography (chloroform

Sources & evidence

ORD record
ord-3a3728422dc64c138fff62ad16688501
Source dataset
uspto-grants-2002_06
Patent number
US06399629B1

Reaction notes

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