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Triethylamine → 1-{2-[{6-[(4-{[4-({[(2S)-1'-{2-[(5R)-3-[3,5-Bis(trifluoromethyl)benzoyl]-5-(4-fluorophenyl)-1,3-oxazolidin-5-yl]ethyl}-2,3-dihydrospiro[indene-1,4'-piperidin]-2-yl]oxy}acetyl)piperazin-1-yl]carbonyl}phenyl)amino]hexanoyl}(methyl)amino]ethyl}piperidin-4-yl biphenyl-2-ylcarbamate

HRID 446598
ノート
印刷プレビュー

反応式

HRID 446598 の反応式
[F:1][C:2]([F:49])([F:48])[C:3]1[CH:4]=[C:5]([CH:41]=[C:42]([C:44]([F:47])([F:46])[F:45])[CH:43]=1)[C:6]([N:8]1[CH2:12][C@@:11]([CH2:20][CH2:21][N:22]2[CH2:27][CH2:26][C:25]3([C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[CH2:29][C@@H:28]3[O:36][CH2:37][C:38]([OH:40])=[O:39])[CH2:24][CH2:23]2)([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)[O:10][CH2:9]1)=[O:7].C(N(CC)CC)C.C(Cl)(=O)C(C)(C)C.[C:64]1([C:106]2[CH:111]=[CH:110][CH:109]=[CH:108][CH:107]=2)[CH:69]=[CH:68][CH:67]=[CH:66][C:65]=1[NH:70][C:71](=[O:105])[O:72][CH:73]1[CH2:78][CH2:77][N:76]([CH2:79][CH2:80][N:81]([CH3:104])[C:82](=[O:103])[CH2:83][CH2:84][CH2:85][CH2:86][CH2:87][NH:88][C:89]2[CH:94]=[CH:93][C:92]([C:95]([N:97]3[CH2:102][CH2:101][NH:100][CH2:99][CH2:98]3)=[O:96])=[CH:91][CH:90]=2)[CH2:75][CH2:74]1>C(Cl)Cl>[CH:38]([O-:40])=[O:39].[NH4+:8].[C:64]1([C:106]2[CH:111]=[CH:110][CH:109]=[CH:108][CH:107]=2)[CH:69]=[CH:68][CH:67]=[CH:66][C:65]=1[NH:70][C:71](=[O:105])[O:72][CH:73]1[CH2:74][CH2:75][N:76]([CH2:79][CH2:80][N:81]([C:82](=[O:103])[CH2:83][CH2:84][CH2:85][CH2:86][CH2:87][NH:88][C:89]2[CH:94]=[CH:93][C:92]([C:95]([N:97]3[CH2:98][CH2:99][N:100]([C:38](=[O:39])[CH2:37][O:36][C@@H:28]4[C:25]5([CH2:26][CH2:27][N:22]([CH2:21][CH2:20][C@:11]6([C:13]7[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=7)[O:10][CH2:9][N:8]([C:6](=[O:7])[C:5]7[CH:41]=[C:42]([C:44]([F:45])([F:46])[F:47])[CH:43]=[C:3]([C:2]([F:49])([F:1])[F:48])[CH:4]=7)[CH2:12]6)[CH2:23][CH2:24]5)[C:35]5[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=5)[CH2:29]4)[CH2:101][CH2:102]3)=[O:96])=[CH:91][CH:90]=2)[CH3:104])[CH2:77][CH2:78]1
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 8471TriethylamineHCID 62493Pivaloyl chlorideHCID 666714801-{2-[Methyl(6-{[4-(piperazin-1-ylcarbonyl)phenyl]amino}hexanoyl)amino]ethyl}piperidin-4-yl biphenyl-2-ylcarbamateHCID 86663420{[(2S)-1'-{2-[(5R)-3-[3,5-Bis(trifluoromethyl)benzoyl]-5-(4-fluorophenyl)-1,3-oxazolidin-5-yl]ethyl}-2,3-dihydrospiro[indene-1,4'-piperidin]-2-yl]oxy}acetic acid

生成物 2

HCID 2723923
Ammonium formate
収率 0.1%
HCID 870995651-{2-[{6-[(4-{[4-({[(2S)-1'-{2-[(5R)-3-[3,5-Bis(trifluoromethyl)benzoyl]-5-(4-fluorophenyl)-1,3-oxazolidin-5-yl]ethyl}-2,3-dihydrospiro[indene-1,4'-piperidin]-2-yl]oxy}acetyl)piperazin-1-yl]carbonyl}phenyl)amino]hexanoyl}(methyl)amino]ethyl}piperidin-4-yl biphenyl-2-ylcarbamate収率 126.1%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

The compound (74 mg, 0.106 mmol) obtained in Example 1j was dissolved in methylene chloride (1.5 mL), triethylamine (17 μL., 0.121 mmol) and pivaloyl chloride (13 μL, 0.105 mmol) were added under ice cooling, and the mixture was stirred at room temperature for 25 minutes. A solution of the compound (66 mg, 0.101 mmol) obtained in Example 92b in methylene chloride (1.5 mL) was added dropwise to the reaction mixture under ice cooling, and the mixture was stirred at room temperature for 2.5 days. The solvent was evaporated under reduced pressure, and the resulting residue was purified by NH silica gel column chromatography (ethyl acetate:methanol=100:0→40:1, v/v) and further by reverse phase preparative column chromatography (Waters; XTerra Prep MS C18 OBD, 5 μm, 30×100 mm) (acetonitrile:0.1% aqueous ammonium formate solution=60:40, v/v) to give the title compound (89 mg; yield, 66%) as a white solid.

後処理

  1. stirringthe mixture was stirred at room temperature for 2.5 days
  2. customThe solvent was evaporated under reduced pressure
  3. customthe resulting residue was purified by NH silica gel column chromatography (ethyl acetate:methanol=100:0→40:1, v/v) and further by reverse phase preparative column chromatography (Waters; XTerra Prep MS C18 OBD, 5 μm, 30×100 mm) (acetonitrile

出典と根拠

ORDレコード
ord-6570b8e178e547609c4152c095e9e6b8
出典データセット
uspto-grants-2013_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08476253B2

反応ノート

読み込み中…

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