Hydrochloric Acid → 3-Amino-N-{4-[(3R,4S,5S)-3-amino-5-methyl-4-(1H-1,2,3-triazol-1-yl)piperidin-1-yl]pyridin-3-yl}-7-ethylquinoline-2-carboxamide

HRID 924518Notes

Reaction equation

HRID 924518 reaction equation
C(OC([NH:8][C@H:9]1[C@@H:14]([N:15]2[CH:19]=[CH:18][N:17]=[N:16]2)[C@@H:13]([CH3:20])[CH2:12][N:11]([C:21]2[CH:26]=[CH:25][N:24]=[CH:23][C:22]=2[NH:27][C:28]([C:30]2[C:39]([NH:40]C(=O)OCC3C=CC=CC=3)=[CH:38][C:37]3[C:32](=[CH:33][C:34]([CH:51]=[CH2:52])=[CH:35][CH:36]=3)[N:31]=2)=[O:29])[CH2:10]1)=O)(C)(C)C.Cl.O1CCOCC1>CO.C1COCC1.[Pd]>[NH2:40][C:39]1[C:30]([C:28]([NH:27][C:22]2[CH:23]=[N:24][CH:25]=[CH:26][C:21]=2[N:11]2[CH2:12][C@H:13]([CH3:20])[C@H:14]([N:15]3[CH:19]=[CH:18][N:17]=[N:16]3)[C@H:9]([NH2:8])[CH2:10]2)=[O:29])=[N:31][C:32]2[C:37]([CH:38]=1)=[CH:36][CH:35]=[C:34]([CH2:51][CH3:52])[CH:33]=2

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 86726957Benzyl {2-[({4-[(3R,4S,5S)-3-[(tert-butoxycarbonyl)amino]-5-methyl-4-(1H-1,2,3-triazol-1-yl)piperidin-1-yl]pyridin-3-yl}amino)carbonyl]-7-vinylquinolin-3-yl}carbamate

Product 1

HCID 867269583-Amino-N-{4-[(3R,4S,5S)-3-amino-5-methyl-4-(1H-1,2,3-triazol-1-yl)piperidin-1-yl]pyridin-3-yl}-7-ethylquinoline-2-carboxamideYield 69.7%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of benzyl {2-[({4-[(3R,4S,5S)-3-[(tert-butoxycarbonyl)amino]-5-methyl-4-(1H-1,2,3-triazol-1-yl)piperidin-1-yl]pyridin-3-yl}amino)carbonyl]-7-vinylquinolin-3-yl}carbamate (5.2 mg, 0.007 mmol) in MeOH (0.29 mL) and THF (0.29 mL) was added a mixture of palladium (2.9 mg) (10% Pd on carbon). The reaction mixture was deoxygenated under reduced pressure and hydrogen was introduced via a balloon. The reaction mixture was stirred at room temperature under hydrogen for 1 h. The mixture was filtered and concentrated under vacuum to give an intermediate. The intermediate was treated with 4.0 M HCl in dioxane (0.074 mL, 0.30 mmol) and stirred at room temperature for 30 min. The solution was then concentrated under reduced pressure. The residue was diluted with MeOH and NH4OH, filtered and purified by preparative LCMS (pH=10 method; XBridge™ preparative C18 5 μm OBD™ column, 30×10 mm, 60 mL/min., eluting with a gradient of MeCN and water with 0.1% NH4OH) to give the desired product as yellow powder (2.3 mg, 66%). LCMS calc. for C25H30N9O (M+H)+: m/z=472.3. Found: 472.3.

Workup

  1. customThe reaction mixture was deoxygenated under reduced pressure and hydrogen
  2. additionwas introduced via a balloon
  3. filtrationThe mixture was filtered
  4. concentrationconcentrated under vacuum
  5. customto give an intermediate
  6. stirringstirred at room temperature for 30 min
  7. concentrationThe solution was then concentrated under reduced pressure
  8. additionThe residue was diluted with MeOH and NH4OH
  9. filtrationfiltered
  10. custompurified by preparative LCMS (pH=10 method
  11. washXBridge™ preparative C18 5 μm OBD™ column, 30×10 mm, 60 mL/min., eluting with a gradient of MeCN and water with 0.1% NH4OH)

Sources & evidence

ORD record
ord-be28017cf84c4dd09d950894beece945
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

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