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 2086313ノート

反応式

HRID 2086313 の反応式
[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

参加物

6

反応物 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

生成物 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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-1f71618128974b01a282b7990d7e821c
出典データセット
uspto-grants-2004_04
特許番号
US06723722B1

反応ノート

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