Hydrochloric Acid → 2-{(2-Cyclopropyl-ethyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-cycloheptanecarboxylic acid methyl ester

HRID 731388ノート

反応式

HRID 731388 の反応式
[CH3:1][O:2][C:3]([C@@H:5]1[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][C@@H:6]1[NH:12][CH2:13][CH2:14][CH:15]1[CH2:17][CH2:16]1)=[O:4].[CH3:18][S:19]([NH:22][C:23]1[CH:38]=[CH:37][C:26]2[NH:27][C:28]([CH2:33][C:34](O)=[O:35])=[N:29][S:30](=[O:32])(=[O:31])[C:25]=2[CH:24]=1)(=[O:21])=[O:20].CN1CCOCC1.Cl.CN(C)CCCN=C=NCC.Cl>CN(C)C=O>[CH3:1][O:2][C:3]([CH:5]1[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH:6]1[N:12]([CH2:13][CH2:14][CH:15]1[CH2:16][CH2:17]1)[C:34](=[O:35])[CH2:33][C:28]1[NH:27][C:26]2[CH:37]=[CH:38][C:23]([NH:22][S:19]([CH3:18])(=[O:21])=[O:20])=[CH:24][C:25]=2[S:30](=[O:31])(=[O:32])[N:29]=1)=[O:4]

参加物

7

反応物 5

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 248585392H-1,2,4-Benzothiadiazine-3-acetic acid, 7-[(methylsulfonyl)amino]-, 1,1-dioxideHCID 69067063cis-2-(2-Cyclopropyl-ethylamino)-cycloheptanecarboxylic acid methyl ester

生成物 1

HCID 576712102-{(2-Cyclopropyl-ethyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-cycloheptanecarboxylic acid methyl ester

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
25 °C

実験手順

The crude cis-2-(2-cyclopropyl-ethylamino)-cycloheptanecarboxylic acid methyl ester (260.5 mg, 1.09 mmol) was mixed with (7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetic acid (prepared as described in Example 1j, 399 mg, 1.2 mmol) and dissolved in N,N-dimethylformamide (9 mL). N-Methylmorpholine (264 μL, 2.4 mmol) was added followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (230 mg, 1.2 mmol). The resulting mixture was shaken at 25° C. overnight. A 1.0 M aqueous hydrochloric acid solution (11 mL) was added (pH=2) and the mixture was extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine (40 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was further dried in vacuo for 5.5 h to afford the crude product, 2-{(2-cyclopropyl-ethyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-cycloheptanecarboxylic acid methyl ester, containing 2-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetylamino]-cycloheptanecarboxylic acid methyl ester as a side product, as a brown oil. This crude product was directly used in the next step without further purification. LC-MS (ESI) calcd for C24H34N4O7S2 554.19, found 555.3 [M+H+] and LC-MS (ESI) calcd for C19H26N4O7S2 486.12, found 487.3 [M+H+]+.

後処理

  1. extractionthe mixture was extracted with ethyl acetate (3×50 mL)
  2. washThe combined organic layers were washed with brine (40 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was further dried in vacuo for 5.5 h

出典と根拠

ORDレコード
ord-cd59557c1ffd42b6a023d633a1caddc4
出典データセット
uspto-grants-2009_09
特許番号
US07582626B2

反応ノート

読み込み中…