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-morpholin-4-ylquinolin-3-yl]carbamate → 3-Amino-N-{4-[(3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-morpholin-4-ylquinoline-2-carboxamide

HRID 924443Notes

Reaction equation

HRID 924443 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][O:57][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[CH2:55][CH2:56][O:57][CH2:58][CH2:59]1)[CH:36]=2

Participants

5

Reactant 2

HCID 86726893Benzyl [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-morpholin-4-ylquinolin-3-yl]carbamateHCID 178418361HCID 178418361, compound

Product 1

HCID 867268943-Amino-N-{4-[(3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}-7-morpholin-4-ylquinoline-2-carboxamide

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-morpholin-4-ylquinolin-3-yl]carbamate (0.0035 g, 0.0042 mmol) in 3 mL of MeOH was hydrogenated under a balloon of hydrogen, in the presence of 3 mg of 10% Pd on carbon, at room temperature for 1 h. The reaction mixture was diluted with 5 mL of MeOH then filtered. The filtrate was concentrated under reduced pressure. 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 volatile solvents were removed under reduced pressure. The residue was dissolved in 4 mL of MeOH and treated with 0.5 mL of NH4OH solution, then filtered. 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 C25H32N7O3 [M+H]+: m/z=478.3. found: 478.3.

Workup

  1. filtrationthen filtered
  2. concentrationThe filtrate was concentrated under reduced pressure
  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. customThe volatile solvents were removed under reduced pressure
  5. dissolutionThe residue was dissolved in 4 mL of MeOH
  6. additiontreated with 0.5 mL of NH4OH solution
  7. filtrationfiltered
  8. customThe filtrate was purified by preparative HPLC (XBridge™ C18 column
  9. washeluting with a gradient of MeCN/water containing 0.1% NH4OH, at a flow rate of 30 mL/min.)

Sources & evidence

ORD record
ord-bfe698618f714d0b8d9fb0826e3e36c2
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

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