Ethyl isonicotinate → Ethyl 1-[[4-[(6-chloro-2-naphthyl)sulfonyl]-1-[methyl[1-(4-pyridinyl)-4-piperidinyl]amino]-6-oxo-2-piperazinyl]carbonyl]-4-piperidinecarboxylate

HRID 2086313Notes

Reaction equation

HRID 2086313 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](O)=[O:37])[CH2:16]1)(=[O:14])=[O:13])[CH:6]=[CH:5]2.[C:39]([O:47][CH2:48][CH3:49])(=[O:46])[C:40]1[CH:45]=[CH:44][N:43]=[CH:42][CH:41]=1.O.ON1C2C=CC=CC=2N=N1.CCN=C=NCCCN(C)C>CN(C=O)C>[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:30]=[CH:31][N:32]=[CH:33][CH:34]=4)[CH2:25][CH2:24]3)[CH:17]([C:36]([N:43]3[CH2:44][CH2:45][CH:40]([C:39]([O:47][CH2:48][CH3:49])=[O:46])[CH2:41][CH2:42]3)=[O:37])[CH2:16]1)(=[O:14])=[O:13])[CH:6]=[CH:5]2

Participants

6

Reactant 4

HCID 15291Ethyl isonicotinateHCID 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 22727045Ethyl 1-[[4-[(6-chloro-2-naphthyl)sulfonyl]-1-[methyl[1-(4-pyridinyl)-4-piperidinyl]amino]-6-oxo-2-piperazinyl]carbonyl]-4-piperidinecarboxylate

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-piperazine carboxylic acid (0.18 g) obtained in Example 110, ethyl isonicotinate (0.068 ml) and 1-hydroxy-1H-benzotriazole monohydrate (0.068 g) in DMF (4.4 ml) was combined with WSC (0.096 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 ethyl 1-[[4-[(6-chloro-2-naphthyl)sulfonyl]-1-[methyl[1-(4-pyridinyl)-4-piperidinyl]amino]-6-oxo-2-piperazinyl]carbonyl]-4-piperidinecarboxylate as a colorless powder. Then a mixture of this material with 1N sodium hydroxide (1.14 ml) and methanol (4.0 ml) was stirred at 40° C. for 30 minutes. The reaction mixture was cooled, and the reaction system was adjusted at pH 5 with 1N hydrochloric acid, and concentrated under reduced pressure. The residue was purified on a CHP-20 column (water→1% conc. aqueous ammonia-containing 25% aqueous solution of acetonitrile) to obtain the title compound (0.07 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-1f71618128974b01a282b7990d7e821c
Source dataset
uspto-grants-2004_04
Patent number
US06723722B1

Reaction notes

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