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

반응식

HRID 446498 반응식
[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

참가 물질

7

반응물 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

생성물 2

HCID 517165Ammonium Acetate수율 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-ylcarbamate수율 53.1%

시약·촉매·용매 1

HCID 887Methanol용매2회

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-6e891253fcb44f4384c50f4d1ce20e8f
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08476253B2

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