Toluene → 1-{2-[{6-[({5-[{3-[({[(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)(methyl)amino]propyl}(methyl)carbamoyl]-2-thienyl}methyl)amino]hexanoyl}(methyl)amino]ethyl}piperidin-4-yl biphenyl-2-ylcarbamate

HRID 446498

反応式

HRID 446498 の反応式
[C:1]1([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8](=[O:28])[O:9][CH:10]1[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][N:18]([C:20](=[O:27])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][NH2:26])[CH3:19])[CH2:12][CH2:11]1.[F:35][C:36]([F:98])([F:97])[C:37]1[CH:38]=[C:39]([CH:90]=[C:91]([C:93]([F:96])([F:95])[F:94])[CH:92]=1)[C:40]([N:42]1[CH2:46][C@@:45]([CH2:54][CH2:55][N:56]2[CH2:61][CH2:60][C:59]3([C:69]4[C:64](=[CH:65][CH:66]=[CH:67][CH:68]=4)[CH2:63][C@@H:62]3[O:70][CH2:71][C:72]([N:74]([CH3:89])[CH2:75][CH2:76][CH2:77][N:78]([CH3:88])[C:79]([C:81]3[S:82][C:83]([CH:86]=O)=[CH:84][CH:85]=3)=[O:80])=[O:73])[CH2:58][CH2:57]2)([C:47]2[CH:52]=[CH:51][C:50]([F:53])=[CH:49][CH:48]=2)[O:44][CH2:43]1)=[O:41].C1(C)C=CC=CC=1.[C:106]([O:109][BH-](OC(=O)C)OC(=O)C)(=[O:108])[CH3:107].[Na+]>CO>[C:106]([O-:109])(=[O:108])[CH3:107].[NH4+:7].[C:1]1([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8](=[O:28])[O:9][CH:10]1[CH2:11][CH2:12][N:13]([CH2:16][CH2:17][N:18]([C:20](=[O:27])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][NH:26][CH2:86][C:83]2[S:82][C:81]([C:79](=[O:80])[N:78]([CH2:77][CH2:76][CH2:75][N:74]([C:72](=[O:73])[CH2:71][O:70][C@@H:62]3[C:59]4([CH2:58][CH2:57][N:56]([CH2:55][CH2:54][C@:45]5([C:47]6[CH:52]=[CH:51][C:50]([F:53])=[CH:49][CH:48]=6)[O:44][CH2:43][N:42]([C:40](=[O:41])[C:39]6[CH:90]=[C:91]([C:93]([F:96])([F:94])[F:95])[CH:92]=[C:37]([C:36]([F:35])([F:98])[F:97])[CH:38]=6)[CH2:46]5)[CH2:61][CH2:60]4)[C:69]4[C:64](=[CH:65][CH:66]=[CH:67][CH:68]=4)[CH2:63]3)[CH3:89])[CH3:88])=[CH:85][CH:84]=2)[CH3:19])[CH2:14][CH2:15]1

参加物

7

反応物 4

HCID 1140TolueneHCID 5049666Sodium triacetoxyborohydrideHCID 666715721-{2-[(6-Aminohexanoyl)(methyl)amino]ethyl}piperidin-4-yl biphenyl-2-ylcarbamateHCID 86663421N-{3-[({[(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)(methyl)amino]propyl}-5-formyl-N-methylthiophene-2-carboxamide

生成物 2

HCID 517165Ammonium Acetate収率 0.1%HCID 469292961-{2-[{6-[({5-[{3-[({[(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)(methyl)amino]propyl}(methyl)carbamoyl]-2-thienyl}methyl)amino]hexanoyl}(methyl)amino]ethyl}piperidin-4-yl biphenyl-2-ylcarbamate収率 53.1%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒2 回

実験手順

The compound (73 mg, 0.157 mmol) obtained in Example 1a and the compound (144 mg, 0.157 mmol) obtained in Example 1l were dissolved in methanol (2 mL), and the mixture was stirred at room temperature for 15 minutes. Toluene was added, then the solvent was evaporated under reduced pressure, sodium triacetoxyborohydride (100 mg, 0.471 mmol) was added to a solution of the resulting residue in methanol (2 mL), and the mixture was stirred at room temperature for 2.5 hours. The solvent was evaporated under reduced pressure, and the resulting residue was purified by NH silica gel column chromatography (ethyl acetate:methanol=60:1→20:1, v/v) and further purified by reverse phase preparative column chromatography (Waters; XTerra Prep MS C18 OBD, 5 μm, 30×100 mm) (acetonitrile:0.1% aqueous ammonium acetate solution=40:60→100:0, v/v) to give the title compound (57 mg; yield, 27%) as a light yellow solid.

後処理

  1. stirringthe mixture was stirred at room temperature for 2.5 hours
  2. customThe solvent was evaporated under reduced pressure
  3. customthe resulting residue was purified by NH silica gel column chromatography (ethyl acetate:methanol=60:1→20:1, v/v)
  4. customfurther purified 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-6e891253fcb44f4384c50f4d1ce20e8f
出典データセット
uspto-grants-2013_07
特許番号
US08476253B2

関連ノート

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