Hydrochloric Acid → 1-{2-[{6-[{4-[{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)(methy)amino]propyl}(methyl)carbamoyl]benzyl}(methyl)amino]hexanoyl}(methyl)amino]ethyl}piperidin-4-yl biphenyl-2-ylcarbamate

HRID 446568Notes

Reaction equation

HRID 446568 reaction equation
[C:1]1([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8]([O:10][CH:11]1[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][N:19]([CH3:40])[C:20](=[O:39])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][N:26]([CH2:28][C:29]2[CH:38]=[CH:37][C:32](C(OC)=O)=[CH:31][CH:30]=2)[CH3:27])[CH2:13][CH2:12]1)=[O:9].[OH-:47].[Na+].Cl.[F:50][C:51]([F:104])([F:103])[C:52]1[CH:53]=[C:54]([CH:96]=[C:97]([C:99]([F:102])([F:101])[F:100])[CH:98]=1)[C:55]([N:57]1[CH2:61][C@@:60]([CH2:69][CH2:70][N:71]2[CH2:76][CH2:75][C:74]3([C:84]4[C:79](=[CH:80][CH:81]=[CH:82][CH:83]=4)[CH2:78][C@@H:77]3[O:85][CH2:86][C:87]([N:89]([CH3:95])[CH2:90][CH2:91][CH2:92][NH:93][CH3:94])=[O:88])[CH2:73][CH2:72]2)([C:62]2[CH:67]=[CH:66][C:65]([F:68])=[CH:64][CH:63]=2)[O:59][CH2:58]1)=[O:56].[CH3:105]O>O.C1(C)C=CC=CC=1>[C:1]1([C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8](=[O:9])[O:10][CH:11]1[CH2:12][CH2:13][N:14]([CH2:17][CH2:18][N:19]([C:20](=[O:39])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][N:26]([CH2:28][C:29]2[CH:38]=[CH:37][C:32]([C:94](=[O:47])[N:93]([CH2:92][CH2:91][CH2:90][N:89]([C:87](=[O:88])[CH2:86][O:85][C@@H:77]3[C:74]4([CH2:73][CH2:72][N:71]([CH2:70][CH2:69][C@:60]5([C:62]6[CH:63]=[CH:64][C:65]([F:68])=[CH:66][CH:67]=6)[O:59][CH2:58][N:57]([C:55](=[O:56])[C:54]6[CH:53]=[C:52]([C:51]([F:50])([F:103])[F:104])[CH:98]=[C:97]([C:99]([F:101])([F:100])[F:102])[CH:96]=6)[CH2:61]5)[CH2:76][CH2:75]4)[C:84]4[C:79](=[CH:80][CH:81]=[CH:82][CH:83]=4)[CH2:78]3)[CH3:95])[CH3:105])=[CH:31][CH:30]=2)[CH3:27])[CH3:40])[CH2:15][CH2:16]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 887MethanolHCID 14798Sodium HydroxideHCID 66671734Methyl 4-{[{6-[(2-{4-[(biphenyl-2-ylcarbamoyl)oxy]piperidin-1-yl}ethyl)(methyl)amino]-6-oxohexyl}(methyl)amino]methyl}benzoateHCID 866634192-{[(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}-N-methyl-N-[3-(methylamino)propyl]acetamide

Product 1

HCID 469286381-{2-[{6-[{4-[{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)(methy)amino]propyl}(methyl)carbamoyl]benzyl}(methyl)amino]hexanoyl}(methyl)amino]ethyl}piperidin-4-yl biphenyl-2-ylcarbamateYield 48%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

The compound (90 mg, 0.14 mmol) obtained in Example 74a was dissolved in a mixed solvent of methanol (1.4 mL) and water (1.4 mL), a 1 N aqueous sodium hydroxide solution (0.214 mL, 0.214 mmol) was added, and the mixture was stirred at room temperature for 3 hours and then at 50° C. for 2 hours. A 1 N aqueous hydrochloric acid solution (0.300 mL) and toluene were added, and then the solvent was evaporated under reduced pressure. The resulting residue and the compound (74 mg, 0.095 mmol) obtained in Example 1k were used to give the title compound (63 mg; yield, 48%) as a white solid according to the method described in Example 11e.

Workup

  1. waitat 50° C. for 2 hours
  2. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-9adb6f170a4b42b88f35e975c093cdaf
Source dataset
uspto-grants-2013_07
Patent number
US08476253B2

Reaction notes

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