HCID 86726910, compound → HCID 86726909, compound

HRID 924465Notes

Reaction equation

HRID 924465 reaction equation
C(OC([NH:8][C@H:9]1[C@H:14]([O:15][Si](C(C)(C)C)(C)C)[C@@H:13]([CH3:23])[CH2:12][N:11]([C:24]2[CH:29]=[CH:28][N:27]=[CH:26][C:25]=2[NH:30][C:31]([C:33]2[C:42]([NH:43]C(=O)OCC3C=CC=CC=3)=[CH:41][C:40]3[C:35](=[CH:36][C:37]([N:54]4[CH2:59][CH2:58][N:57]([CH3:60])[CH2:56][CH2:55]4)=[CH:38][CH:39]=3)[N:34]=2)=[O:32])[CH2:10]1)=O)(C)(C)C.[H][H]>CO.[Pd]>[NH2:43][C:42]1[C:33]([C:31]([NH:30][C:25]2[CH:26]=[N:27][CH:28]=[CH:29][C:24]=2[N:11]2[CH2:12][C@H:13]([CH3:23])[C@@H:14]([OH:15])[C@H:9]([NH2:8])[CH2:10]2)=[O:32])=[N:34][C:35]2[C:40]([CH:41]=1)=[CH:39][CH:38]=[C:37]([N:54]1[CH2:59][CH2:58][N:57]([CH3:60])[CH2:56][CH2:55]1)[CH:36]=2

Participants

5

Reactant 2

HCID 86726910HCID 86726910, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 86726909HCID 86726909, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent2×

Procedure

A mixture of benzyl [2-({[4-((3R,4R,5S)-3-[(tert-butoxycarbonyl)amino]-4-{[tert-butyl(dimethyl)silyl]oxy}-5-methylpiperidin-1-yl)pyridin-3-yl]amino}carbonyl)-7-(4-methylpiperazin-1-yl)quinolin-3-yl]carbamate (0.0055 g, 0.0066 mmol) in 3 mL of MeOH was hydrogenated in the presence of 3 mg of 10% Pd on carbon under a balloon of hydrogen at room temperature for 1 h. The mixture was diluted with 5 mL of MeOH then filtered. The filtrate was concentrated and the resulting residue was treated with 2 mL of MeOH and 2 mL of 4 M HCl in dioxane at room temperature for 1 h. The solution was concentrated under reduced pressure, the residue was dissolved in 4 mL of MeOH and 0.5 mL of NH4OH solution, then filtered through a diatomaceous earth plug. The filtrate was purified by preparative HPLC (XBridge™ C18 column, eluting with a gradient of MeCN/water containing 0.1% NH4OH, at a flow rate of 30 mL/min.) to afford the title compound. LCMS calc. for C26H35N8O2 [M+H]+: m/z=491.3. found: 491.3.

Workup

  1. filtrationthen filtered
  2. concentrationThe filtrate was concentrated
  3. additionthe resulting residue was treated with 2 mL of MeOH and 2 mL of 4 M HCl in dioxane at room temperature for 1 h
  4. concentrationThe solution was concentrated under reduced pressure
  5. dissolutionthe residue was dissolved in 4 mL of MeOH
  6. filtration0.5 mL of NH4OH solution, then filtered through a diatomaceous earth plug
  7. customThe filtrate was purified by preparative HPLC (XBridge™ C18 column
  8. washeluting with a gradient of MeCN/water containing 0.1% NH4OH, at a flow rate of 30 mL/min.)

Sources & evidence

ORD record
ord-ebaac60688f640f58844e555e674da99
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

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