Triethylamine → 9-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-one

HRID 1972470ノート

反応式

HRID 1972470 の反応式
[O:1]=[C:2]1[CH2:9][CH:8]2[N:10]([CH2:11][C@H:12]3[CH2:17][N:16](C([O-])=O)[CH2:15][CH2:14][N:13]3C([O-])=O)[CH:4]([CH2:5][O:6][CH2:7]2)[CH2:3]1.[OH:24][CH:25]1[CH2:32][CH:31]2[N:33]([CH2:34][C@H:35]3[CH2:40][N:39](C([O-])=O)[CH2:38][CH2:37][N:36]3C([O-])=O)[CH:27]([CH2:28][O:29][CH2:30]2)[CH2:26]1.O1CCOCC1.C(N(CC)CC)C.[N+:60]([C:63]1[S:67][C:66]([S:68](Cl)(=[O:70])=[O:69])=[CH:65][CH:64]=1)([O-:62])=[O:61]>CCOC(C)=O.Cl.C(Cl)Cl>[N+:60]([C:63]1[S:67][C:66]([S:68]([N:16]2[CH2:15][CH2:14][NH:13][C@@H:12]([CH2:11][N:10]3[CH:8]4[CH2:9][CH:2]([OH:1])[CH2:3][CH:4]3[CH2:5][O:6][CH2:7]4)[CH2:17]2)(=[O:70])=[O:69])=[CH:65][CH:64]=1)([O-:62])=[O:61].[N+:60]([C:63]1[S:67][C:66]([S:68]([N:39]2[CH2:38][CH2:37][NH:36][C@@H:35]([CH2:34][N:33]3[CH:31]4[CH2:32][C:25](=[O:24])[CH2:26][CH:27]3[CH2:28][O:29][CH2:30]4)[CH2:40]2)(=[O:70])=[O:69])=[CH:65][CH:64]=1)([O-:62])=[O:61]

参加物

10

反応物 5

HCID 8471TriethylamineHCID 312751,4-DioxaneHCID 217873475-Nitrothiophene-2-sulfonyl chlorideHCID 86670350(2S)-2-((7-oxo-3-oxa-9-azabicyclo[3.3.1]non-9-yl)methyl)-1,4-piperazinedicarboxylateHCID 86670351(2S)-2-((7-hydroxy-3-oxa-9-azabicyclo[3.3.1]non-9-yl)methyl)-1,4-piperazinedicarboxylate

生成物 2

HCID 665826279-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-oneHCID 706562379-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-ol

試薬・触媒・溶媒 3

HCID 313Hydrochloric Acid溶媒HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
70 °C

実験手順

A 100-mL round-bottomed flask was charged with (2S)-2-((7-oxo-3-oxa-9-azabicyclo[3.3.1]non-9-yl)methyl)-1,4-piperazinedicarboxylate and (2S)-2-((7-hydroxy-3-oxa-9-azabicyclo[3.3.1]non-9-yl)methyl)-1,4-piperazinedicarboxylate (endo) (0.5 g) in EtOAc (20 mL) and 4N HCl in dioxane (0.85 mL, 3.4 mmol) was added. The reaction was heated to 70° C. for 2 h and after this time the precipitate was filtered, collected and dried. This material was dissolved in CH2Cl2 (10 mL). Triethylamine (0.75 mL, 5.4 mmol) followed by 5-nitrothiophene-2-sulfonyl chloride (0.26 g, 1.13 mmol, Enamine Building Blocks, Kiev, Ukraine) as a solution in CH2Cl2 (5 mL) were then added. After 10 min at room temperature, the reaction was concentrated onto silica and purified via column chromatography (40 g silica gel, 0 to 10% MeOH in CH2Cl2) to give 9-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-ol (endo) and 9-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-one (0.54 g).

後処理

  1. additionwas added
  2. filtrationafter this time the precipitate was filtered
  3. customcollected
  4. customdried
  5. dissolutionThis material was dissolved in CH2Cl2 (10 mL)
  6. additionwere then added
  7. concentrationthe reaction was concentrated onto silica
  8. custompurified via column chromatography (40 g silica gel, 0 to 10% MeOH in CH2Cl2)

出典と根拠

ORDレコード
ord-6adb357220bd4774b02cab9578e88527
出典データセット
uspto-grants-2013_04
特許番号
US08431563B2

反応ノート

読み込み中…