Benzyl {(3S)-1-[3-({[3-{[(benzyloxy)carbonyl]amino}-7-(cyanomethyl)quinolin-2-yl]carbonyl}amino)pyridin-4-yl]piperidin-3-yl}carbamate → 3-Amino-N-{4-[(3S)-3-aminopiperidin-1-yl]pyridin-3-yl}-7-(cyanomethyl)quinoline-2-carboxamide

HRID 924375Notes

Reaction equation

HRID 924375 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][CH:18]=[C:17]([CH2:22][C:23]#[N: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][CH:18]=[C:17]([CH2:22][C:23]#[N:24])[CH:16]=2

Participants

4

Reactant 1

HCID 86726860Benzyl {(3S)-1-[3-({[3-{[(benzyloxy)carbonyl]amino}-7-(cyanomethyl)quinolin-2-yl]carbonyl}amino)pyridin-4-yl]piperidin-3-yl}carbamate

Product 1

HCID 778442733-Amino-N-{4-[(3S)-3-aminopiperidin-1-yl]pyridin-3-yl}-7-(cyanomethyl)quinoline-2-carboxamideYield 9%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a solution of benzyl {(3S)-1-[3-({[3-{[(benzyloxy)carbonyl]amino}-7-(cyanomethyl)quinolin-2-yl]carbonyl}amino)pyridin-4-yl]piperidin-3-yl}carbamate (65.8 mg, 0.0982 mmol) in MeOH (2.0 mL), 10 wt % Pd on carbon (15.4 mg, 0.0145 mmol) was added. The mixture was 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 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 (3.4 mg, 9%). LCMS calc. for C22H24N7O (M+H)+: m/z=402.2. found 402.2. 1H NMR (400 MHz, DMSO-d6) δ 9.41 (s, 1H), 8.27 (d, J=5.3 Hz, 1H), 7.85 (s, 1H), 7.75 (d, J=8.7 Hz, 1H), 7.57 (s, 1H), 7.41 (d, J=8.5 Hz, 1H), 7.17 (d, J=5.3 Hz, 1H), 6.98 (s, 2H), 4.23 (s, 2H), 3.25-3.18 (m, 1H), 3.18-3.03 (m, 2H), 2.78-2.58 (m, 1H), 2.47-2.41 (m, 1H), 2.08-1.95 (m, 1H), 1.95-1.76 (m, 2H), 1.22 (s, 1H) ppm.

Workup

  1. filtrationThe reaction mixture was filtered through a pad of diatomaceous earth (eluted with MeOH)
  2. concentrationconcentrated 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-efa4b0ca940f4695ab3ca4492bc63cbd
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

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