1-Hydroxybenzotriazole → N-(N-Acetyl-tyrosinyl-valinyl-pipecolyl)-4-amino-5-benzyloxy-2-oxotetrahydrofuran

HRID 2257395Notes

Reaction equation

HRID 2257395 reaction equation
[C:1]([NH:4][C@H:5]([C:14]([NH:16][C@H:17]([C:21]([OH:23])=O)[CH:18]([CH3:20])[CH3:19])=[O:15])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=1)(=[O:3])[CH3:2].[NH:24]1[CH2:46][CH2:45][CH2:44][CH2:43][CH:25]1[C:26]([NH:28][CH:29]1[CH:33]([O:34][CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[O:32][C:31](=[O:42])[CH2:30]1)=[O:27].ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>CN(C)C=O.C(OCC)(=O)C.ClCCl>[C:1]([NH:4][C@H:5]([C:14]([NH:16][C@H:17]([C:21]([N:24]1[CH2:46][CH2:45][CH2:44][CH2:43][CH:25]1[C:26]([NH:28][CH:29]1[CH:33]([O:34][CH2:35][C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)[O:32][C:31](=[O:42])[CH2:30]1)=[O:27])=[O:23])[CH:18]([CH3:19])[CH3:20])=[O:15])[CH2:6][C:7]1[CH:8]=[CH:9][C:10]([OH:13])=[CH:11][CH:12]=1)(=[O:3])[CH3:2]

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 22875497N-Acetyl-tyrosinyl-valineHCID 66756117N-Pipecolyl-4-amino-5-benzyloxy-2-oxotetrahydrofuran

Product 1

HCID 66756123N-(N-Acetyl-tyrosinyl-valinyl-pipecolyl)-4-amino-5-benzyloxy-2-oxotetrahydrofuranYield 45.7%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

N-Acetyl-tyrosinyl-valine (464 mg, 1.44 mmol) and N-Pipecolyl-4-amino-5-benzyloxy-2-oxotetrahydrofuran (412 mg, 1.3 mmol) were dissolved in 5 ml each of dimethylformamide and dichloromethane and cooled to 0° C. To the cooled solution was added 1-hydroxybenzotriazole (HOBT; 210 mg, 1.56 mmol) followed by the addition of 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride (EDC; 326 mg, 1.7 mmol). After stirring for 18 hours, the mixture was diluted with ethyl acetate and washed with water, 10% sodium hydrogen sulfate, 10% sodium bicarbonate, and water. The organic layer was concentrated to give a crude solid that was purified by flash chromatography (SiO2) eluting with 94:6:1 (dichloromethane:isopropanol:pyridine) to give 370 mg of the title compound.

Workup

  1. washwashed with water, 10% sodium hydrogen sulfate, 10% sodium bicarbonate, and water
  2. concentrationThe organic layer was concentrated
  3. customto give a crude solid that
  4. customwas purified by flash chromatography (SiO2)
  5. washeluting with 94:6:1 (dichloromethane:isopropanol:pyridine)

Sources & evidence

ORD record
ord-c68a662606244e05978782afb0a86643
Source dataset
uspto-grants-1997_08
Patent number
US05656627

Reaction notes

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