Benzyl [(3S)-1-(3-{[(3-{[(benzyloxy)carbonyl]amino}-6-fluoro-7-vinylquinolin-2-yl)carbonyl]amino}pyridin-4-yl)piperidin-3-yl]carbamate → 3-Amino-N-{4-[(3S)-3-aminopiperidin-1-yl]pyridin-3-yl}-7-ethyl-6-fluoroquinoline-2-carboxamide

HRID 924383Notes

Reaction equation

HRID 924383 reaction equation
C(OC([NH:11][C:12]1[C:13]([C:25]([NH:27][C:28]2[CH:29]=[N:30][CH:31]=[CH:32][C:33]=2[N:34]2[CH2:39][CH2:38][CH2:37][C@H:36]([NH:40]C(=O)OCC3C=CC=CC=3)[CH2:35]2)=[O:26])=[N:14][C:15]2[C:20]([CH:21]=1)=[CH:19][C:18]([F:22])=[C:17]([CH:23]=[CH2:24])[CH:16]=2)=O)C1C=CC=CC=1>CO.[Pd]>[NH2:11][C:12]1[C:13]([C:25]([NH:27][C:28]2[CH:29]=[N:30][CH:31]=[CH:32][C:33]=2[N:34]2[CH2:39][CH2:38][CH2:37][C@H:36]([NH2:40])[CH2:35]2)=[O:26])=[N:14][C:15]2[C:20]([CH:21]=1)=[CH:19][C:18]([F:22])=[C:17]([CH2:23][CH3:24])[CH:16]=2

Participants

4

Reactant 1

HCID 86726866Benzyl [(3S)-1-(3-{[(3-{[(benzyloxy)carbonyl]amino}-6-fluoro-7-vinylquinolin-2-yl)carbonyl]amino}pyridin-4-yl)piperidin-3-yl]carbamate

Product 1

HCID 778442743-Amino-N-{4-[(3S)-3-aminopiperidin-1-yl]pyridin-3-yl}-7-ethyl-6-fluoroquinoline-2-carboxamideYield 14%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a solution of benzyl [(3S)-1-(3-{[(3-{[(benzyloxy)carbonyl]amino}-6-fluoro-7-vinylquinolin-2-yl)carbonyl]amino}pyridin-4-yl)piperidin-3-yl]carbamate (242.7 mg, 0.3597 mmol) in MeOH (7.00 mL), 10 wt % Pd on carbon (66.7 mg, 0.0627 mmol) was added. The mixture was then stirred at room temperature under hydrogen (1 atm.) for 15 h. The reaction mixture was filtered through a pad of diatomaceous earth (eluted with MeOH) and was then concentrated under reduced pressure. The resulting residue was purified using RP-HPLC (XBridge™ C18 column, eluting with a gradient of MeCN/water containing 0.1% NH4OH, at a flow rate of 30 mL/min.) to give the title compound as a yellow solid (20.2 mg, 14%). LCMS calc. for C22H26FN6O (M+H)+: m/z=409.2. found 409.2. 1H NMR (500 MHz, DMSO-d6) δ 9.38 (s, 1H), 8.28 (d, J=5.2 Hz, 1H), 7.73 (d, J=7.5 Hz, 1H), 7.53-7.44 (m, 2H), 7.17 (d, J=5.2 Hz, 1H), 6.95 (s, 2H), 3.56-3.13 (m, 2H), 3.13-3.01 (m, 1H), 2.82-2.67 (m, 3H), 2.55 (m, J=9.6 Hz, 1H), 2.03-1.94 (m, 1H), 1.94-1.79 (m, 2H), 1.37-1.32 (m, 1H), 1.29 (t, J=7.5 Hz, 3H) ppm.

Workup

  1. filtrationThe reaction mixture was filtered through a pad of diatomaceous earth (eluted with MeOH)
  2. concentrationwas then concentrated under reduced pressure
  3. customThe resulting residue was purified
  4. washeluting with a gradient of MeCN/water containing 0.1% NH4OH, at a flow rate of 30 mL/min.)

Sources & evidence

ORD record
ord-54e6a97f1faa44e7ae4cd609269745c2
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

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