1-Hydroxybenzotriazole → 1-[trans-4-(N-tert-Butoxycarbonylglycylamino)-N-tert-Butoxycarbonyl-L-Prolyl]4-(4-Phenylbutanoyl)piperazine

HRID 2185473Notes

Reaction equation

HRID 2185473 reaction equation
Cl.CN(C)CCCN=C=NCC.[C:13]([O:17][C:18]([NH:20][CH2:21][C:22]([NH:24][C@H:25]1[CH2:29][N:28]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[C@H:27]([C:37](O)=[O:38])[CH2:26]1)=[O:23])=[O:19])([CH3:16])([CH3:15])[CH3:14].[C:40]1([CH2:46][CH2:47][CH2:48][C:49]([N:51]2[CH2:56][CH2:55][N:54](C([O-])=O)[CH2:53][CH2:52]2)=[O:50])[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.ON1C2C=CC=CC=2N=N1>ClCCl.C(N(CC)CC)C>[C:13]([O:17][C:18]([NH:20][CH2:21][C:22]([NH:24][C@H:25]1[CH2:29][N:28]([C:30]([O:32][C:33]([CH3:36])([CH3:34])[CH3:35])=[O:31])[C@H:27]([C:37]([N:54]2[CH2:55][CH2:56][N:51]([C:49](=[O:50])[CH2:48][CH2:47][CH2:46][C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[CH2:52][CH2:53]2)=[O:38])[CH2:26]1)=[O:23])=[O:19])([CH3:15])([CH3:16])[CH3:14]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 21341559trans-4-(N-tert-butoxycarbonylglycyl)amino-N-tert-butoxycarbonyl-L-prolineHCID 224587744-(4-Phenylbutanoyl)l-piperazinecarboxylate

Product 1

HCID 701756021-[trans-4-(N-tert-Butoxycarbonylglycylamino)-N-tert-Butoxycarbonyl-L-Prolyl]4-(4-Phenylbutanoyl)piperazineYield 100.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

Triethylamine (72 μL) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (98.9 mg) were added to a solution of trans-4-(N-tert-butoxycarbonylglycylamino)-N-tert-butoxycarbonyl-L-proline (Compound D103 (B), 144.9 mg), 4-(4-phenylbutanoyl)l-piperazinecarboxylate (B, 100 mg), and 1-hydroxybenzotriazole (65 mg) in dichloromethane at room temperature. After stirring at room temperature for 20 hr, the reaction mixture was partitioned between ethyl acetate and 1 N hydrochloric acid. The organic layer was washed with saturated sodium hydrogen carbonate and brine. After drying over anhydrous sodium sulfate, the organic layer was evaporated in vacuo. The residue was purified by silica gel column chromatography (chloroform:methanol=50:1 to 20:1) to give the titled compound (220 mg) as a white powder: 1H-NMR(400 MHz, CDCl3) δ 1.46 (s, 18H), 1.99 (t, 2H), 2.33 (m, 2H), 2.69 (t, 2H), 3.39-3.85 (m, 13H), 7.18-7.31(m, 5H).

Workup

  1. customthe reaction mixture was partitioned between ethyl acetate and 1 N hydrochloric acid
  2. washThe organic layer was washed with saturated sodium hydrogen carbonate and brine
  3. dry with materialAfter drying over anhydrous sodium sulfate
  4. customthe organic layer was evaporated in vacuo
  5. customThe residue was purified by silica gel column chromatography (chloroform:methanol=50:1 to 20:1)

Sources & evidence

ORD record
ord-7680b2d3fe0341098b38d11cabbb514b
Source dataset
uspto-grants-2002_06
Patent number
US06399629B1

Reaction notes

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