Hydrochloric Acid → (R,S)-[4-[2-Methoxycarbonylamino-4-oxo-4-(4-pyridin-4-ylpiperazin-1-yl)butyryl]-3-methoxycarbonylmethyl-2-oxopiperazin-1-yl]acetic Acid Hydrochloride

HRID 1066571Notes

Reaction equation

HRID 1066571 reaction equation
FC(F)(F)[C:3](O)=[O:4].[NH2:8][C@@H:9]([CH2:28][C:29](=[O:42])[N:30]1[CH2:35][CH2:34][N:33]([C:36]2[CH:41]=[CH:40][N:39]=[CH:38][CH:37]=2)[CH2:32][CH2:31]1)[C:10]([N:12]1[CH2:17][CH2:16][N:15]([CH2:18][C:19]([OH:21])=[O:20])[C:14](=[O:22])[C@@:13]1([CH:25]=[C:26]=[O:27])OC)=[O:11].C(=O)([O-])O.[Na+].[Cl:48][C:49]([O:51][CH3:52])=[O:50].Cl>O1CCOCC1.O>[ClH:48].[CH3:52][O:51][C:49]([NH:8][C@@H:9]([CH2:28][C:29](=[O:42])[N:30]1[CH2:31][CH2:32][N:33]([C:36]2[CH:37]=[CH:38][N:39]=[CH:40][CH:41]=2)[CH2:34][CH2:35]1)[C:10]([N:12]1[CH2:17][CH2:16][N:15]([CH2:18][C:19]([OH:21])=[O:20])[C:14](=[O:22])[C@H:13]1[CH2:25][C:26]([O:4][CH3:3])=[O:27])=[O:11])=[O:50]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6586Methyl chloroformateHCID 516892Sodium BicarbonateHCID 86756995(r,s)-[4-[2-Amino-4-oxo-4-[4-(pyridin-4-yl)piperazin-1-yl]butyryl]-3-methoxy-carbonylmethyl-2-oxopiperazin-1-yl]acetic acid trifluoroacetic acid salt

Product 1

HCID 70066898(R,S)-[4-[2-Methoxycarbonylamino-4-oxo-4-(4-pyridin-4-ylpiperazin-1-yl)butyryl]-3-methoxycarbonylmethyl-2-oxopiperazin-1-yl]acetic Acid Hydrochloride

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a mixture of (R,S)-[4-[2-amino-4-oxo-4-[4-(pyridin-4-yl)piperazin-1-yl]butyryl]-3-methoxy-carbonylmethyl-2-oxopiperazin-1-yl]acetic acid trifluoroacetic acid salt (0.30 g) produced in Working Example 21, an aqueous solution of sodium hydrogen carbonate (0.18 g), water (3 ml) and 1,4-dioxane (3 ml) was added methyl chloroformate (0.051 ml) and the solution was stirred for 1 hour at room temperature. To the reaction solution was added 1N hydrochloric acid and the solution was adjusted to pH 3, which was then concentrated. The concentrate was purified by means of CHP-20 column chromatography (eluent:H2O→10% acetonitrile aqueous solution). The objected fraction was concentrated and subjected to lyophilization to give the titled compound (0.25 g) as a white amorphous powdery product.

Workup

  1. customproduced in Working Example 21
  2. concentrationwas then concentrated
  3. customThe concentrate was purified by means of CHP-20 column chromatography (eluent:H2O→10% acetonitrile aqueous solution)
  4. concentrationThe objected fraction was concentrated

Sources & evidence

ORD record
ord-561f9804f7b3411b840f0d64bac6a786
Source dataset
uspto-grants-2001_06
Patent number
US06242600B1

Reaction notes

Loading…