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 2086313노트

반응식

HRID 2086313 반응식
[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

참가 물질

6

반응물 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

생성물 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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-1f71618128974b01a282b7990d7e821c
출처 데이터셋
uspto-grants-2004_04
특허 번호
US06723722B1

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