Morpholine → 4-[(6-Chloro-2-naphthyl)sulfonyl]-1-[methyl[1-(4-pyridinyl)-4-piperidinyl]amino]-6-(4-morpholinylcarbonyl)-2-piperazinone Hydrochloride

HRID 2086308Notes

Reaction equation

HRID 2086308 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([S:12]([N:15]1[CH2:20][C:19](=[O:21])[N:18]([N:22]([CH3:35])[CH:23]3[CH2:28][CH2:27][N:26]([C:29]4[CH:34]=[CH:33][N:32]=[CH:31][CH:30]=4)[CH2:25][CH2:24]3)[CH:17]([C:36]([OH:38])=O)[CH2:16]1)(=[O:14])=[O:13])[CH:6]=[CH:5]2.[NH:39]1[CH2:44][CH2:43][O:42][CH2:41][CH2:40]1.O.ON1C2C=CC=CC=2N=N1.CCN=C=NCCCN(C)C>CN(C=O)C>[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([S:12]([N:15]1[CH2:16][CH:17]([C:36]([N:39]3[CH2:44][CH2:43][O:42][CH2:41][CH2:40]3)=[O:38])[N:18]([N:22]([CH3:35])[CH:23]3[CH2:24][CH2:25][N:26]([C:29]4[CH:30]=[CH:31][N:32]=[CH:33][CH:34]=4)[CH2:27][CH2:28]3)[C:19](=[O:21])[CH2:20]1)(=[O:13])=[O:14])[CH:6]=[CH:5]2

Participants

6

Reactant 4

HCID 8083MorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 27960291-Hydroxybenzotriazole hydrateHCID 227272374-[(6-Chloro-2-naphthyl)sulfonyl)-1-[methyl[1-(4-pyridinyl)-4-piperidinyl]amino]-6-oxo-2-piperazinecarboxylic Acid

Product 1

HCID 227272404-[(6-Chloro-2-naphthyl)sulfonyl]-1-[methyl[1-(4-pyridinyl)-4-piperidinyl]amino]-6-(4-morpholinylcarbonyl)-2-piperazinone HydrochlorideYield 99.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 4-[(6-chloro-2-naphthyl)sulfonyl)-1-[methyl[1-(4-pyridinyl)-4-piperidinyl]amino]-6-oxo-2-piperazinecarboxylic acid (0.22 g) obtained in Example 110, morpholine (0.048 g) and 1-hydroxy-1H-benzotriazole monohydrate (0.085 g) in DMF (4.4 ml) was combined with WSC (0.12 g) and stirred at room temperature for 18 hours. The reaction mixture was concentrated under reduced pressure, and partitioned between saturated aqueous sodium bicarbonate and methylene chloride. The organic phase was dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified on a CHP-20 column (water→1% 1N hydrochloric acid-containing 30% aqueous solution of acetonitrile) to obtain the title compound (0.13 g) as a colorless powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. custompartitioned between saturated aqueous sodium bicarbonate and methylene chloride
  3. dry with materialThe organic phase was dried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified on a CHP-20 column (water→1% 1N hydrochloric acid-containing 30% aqueous solution of acetonitrile)

Sources & evidence

ORD record
ord-26ddf95ae9ac45749aefe10ddbadc067
Source dataset
uspto-grants-2004_04
Patent number
US06723722B1

Reaction notes

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