Acetic Acid → 3-Amino-N-{4-[(3S)-3-aminopiperidin-1-yl]pyridin-3-yl}-7-(1-fluoroethyl)quinoline-2-carboxamide

HRID 924394Notes

Reaction equation

HRID 924394 reaction equation
C(OC([NH:8][C@H:9]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[CH:20]=[CH:19][N:18]=[CH:17][C:16]=2[NH:21][C:22]([C:24]2[C:33]([NH:34]C(=O)OCC3C=CC=CC=3)=[CH:32][C:31]3[C:26](=[CH:27][C:28]([CH:45](O)[CH3:46])=[CH:29][CH:30]=3)[N:25]=2)=[O:23])[CH2:10]1)=O)(C)(C)C.C(N(S(F)(F)[F:54])CC)C.C([O-])(O)=O.[Na+].Br.CC(O)=O>C(Cl)Cl>[NH2:34][C:33]1[C:24]([C:22]([NH:21][C:16]2[CH:17]=[N:18][CH:19]=[CH:20][C:15]=2[N:11]2[CH2:12][CH2:13][CH2:14][C@H:9]([NH2:8])[CH2:10]2)=[O:23])=[N:25][C:26]2[C:31]([CH:32]=1)=[CH:30][CH:29]=[C:28]([CH:45]([F:54])[CH3:46])[CH:27]=2

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 260Hydrogen BromideHCID 123472(Diethylamino)sulfur trifluorideHCID 516892Sodium BicarbonateHCID 86726871Benzyl [2-{[(4-{(3S)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}pyridin-3-yl)amino]carbonyl}-7-(1-hydroxyethyl)quinolin-3-yl]carbamate

Product 1

HCID 778442773-Amino-N-{4-[(3S)-3-aminopiperidin-1-yl]pyridin-3-yl}-7-(1-fluoroethyl)quinoline-2-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

Benzyl [2-{[(4-{(3S)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}pyridin-3-yl)amino]carbonyl}-7-(1-hydroxyethyl)quinolin-3-yl]carbamate (8.0 mg, 0.012 mmol) (from Example 15, step 6) was dissolved in DCM (0.3 mL), cooled to −78° C., and then treated with diethylaminosulfur trifluoride (50 mg, 0.3 mmol). The resulting reaction mixture allowed to warm to room temperature and stirred at room temperature for 2 h. The reaction mixture was poured into ice-water containing NaHCO3, extracted three times with DCM, dried over Na2SO4, filtered and concentrated under reduced pressure. HBr in AcOH (8.0 M; 0.20 mL, 1.6 mmol) was added to the residue. The reaction mixture was stirred at room temperature for 30 min., and then concentrated under reduced pressure. The residue was diluted with MeOH and neutralized with small amounts of NH4OH. The mixture was filtered and purified by preparative LC-MS (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 NH4OH) to give the title compound. LCMS calc. for C22H26FN6O (M+H)+: m/z=409.1. Found: 409.0.

Workup

  1. customThe resulting reaction mixture
  2. temperatureto warm to room temperature
  3. extractionextracted three times with DCM
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. stirringThe reaction mixture was stirred at room temperature for 30 min.
  8. concentrationconcentrated under reduced pressure
  9. additionThe residue was diluted with MeOH and neutralized with small amounts of NH4OH
  10. filtrationThe mixture was filtered
  11. custompurified by preparative LC-MS (pH=10 method
  12. washXBridge™ preparative C18 5 μm OBD™ column, 30×10 mm, 60 mL/min., eluting with a gradient of MeCN and water with NH4OH)

Sources & evidence

ORD record
ord-921ae9769cb140ec9524bbbcdc915b8f
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

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