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

Reaction equation

HRID 446498 reaction equation
[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

Participants

7

Reactant 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

Product 2

HCID 517165Ammonium AcetateYield 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-ylcarbamateYield 53.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-6e891253fcb44f4384c50f4d1ce20e8f
Source dataset
uspto-grants-2013_07
Patent number
US08476253B2

Linked notes

Loading…