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

HRID 924395Notes

Reaction equation

HRID 924395 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)=[CH:29][CH:30]=3)[N:25]=2)=[O:23])[CH2:10]1)=O)(C)(C)C.[NH:47]1[CH2:51][CH2:50][CH2:49][CH2:48]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[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]([CH2:45][N:47]1[CH2:51][CH2:50][CH2:49][CH2:48]1)[CH:27]=2

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 260Hydrogen BromideHCID 31268PyrrolidineHCID 5049666Sodium triacetoxyborohydrideHCID 86726870Benzyl (2-{[(4-{(3S)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}pyridin-3-yl)amino]carbonyl}-7-formylquinolin-3-yl)carbamate

Product 1

HCID 778443383-Amino-N-{4-[(3S)-3-aminopiperidin-1-yl]pyridin-3-yl}-7-(pyrrolidin-1-ylmethyl)quinoline-2-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Benzyl (2-{[(4-{(3S)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}pyridin-3-yl)amino]carbonyl}-7-formylquinolin-3-yl)carbamate (0.008 g, 0.01 mmol) (from Example 15, step 5) was mixed with pyrrolidine, DCM (0.20 mL) and sodium triacetoxyborohydride (0.020 g, 0.094 mmol). The reaction mixture was stirred at room temperature for 2 h. HBr in AcOH (8.0 M; 0.20 mL, 1.6 mmol) was added and the reaction mixture was stirred at room temperature for 30 min. After concentration to remove the solvent, the crude product was diluted with MeOH and neutralized with a small amount 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 C25H32N7O (M+H)+: m/z=446.2. Found: 446.1.

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 30 min
  2. concentrationAfter concentration
  3. customto remove the solvent
  4. additionthe crude product was diluted with MeOH
  5. filtrationThe mixture was filtered
  6. custompurified by preparative LC-MS (pH=10 method
  7. 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-9887078b4db64cb78c53e657d406b58e
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

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