Phenyl N-hydroxycarbamate → 4-[(3,5-Dimethyl-pyridin-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-piperidine-1-carboxylic acid hydroxyamide

HRID 1592626Notes

Reaction equation

HRID 1592626 reaction equation
[CH3:1][C:2]1[C:3]([CH2:9][N:10]([CH:21]2[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]2)[CH:11]2[C:20]3[N:19]=[CH:18][CH:17]=[CH:16][C:15]=3[CH2:14][CH2:13][CH2:12]2)=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1.C1([O:33][C:34]([NH:36][OH:37])=O)C=CC=CC=1>C1COCC1>[OH:37][NH:36][C:34]([N:24]1[CH2:23][CH2:22][CH:21]([N:10]([CH2:9][C:3]2[C:2]([CH3:1])=[CH:7][C:6]([CH3:8])=[CH:5][N:4]=2)[CH:11]2[C:20]3[N:19]=[CH:18][CH:17]=[CH:16][C:15]=3[CH2:14][CH2:13][CH2:12]2)[CH2:26][CH2:25]1)=[O:33]

Participants

4

Reactant 2

HCID 148233Phenyl N-hydroxycarbamateHCID 67272658(3,5-Dimethyl-pyridin-2-ylmethyl)-piperidin-4-yl-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine

Product 1

HCID 589969624-[(3,5-Dimethyl-pyridin-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-piperidine-1-carboxylic acid hydroxyamideYield 34%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (3,5-dimethyl-pyridin-2-ylmethyl)-piperidin-4-yl-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine (150.0 mg, 0.428 mmol) in THF (5 mL) was added hydroxylamine carboxylic acid phenyl ester (75 mg, 0.449 mmol) and stirred for 17.5 h at reflux. The mixture was cooled to ambient temperature and concentrated in vacuo. Purification by flash chromatography on silica gel using CH2Cl2/MeOH/NH4OH (89:10:1) followed by purification by radial chromatography using CH2Cl2/MeOH/NH4OH (94:5:1) afforded COMPOUND 369 (59 mg, 34%) as white solid. 1H NMR (CDCl3) δ1.54-1.72 (m, 3H), 1.81-2.05 (m, 5H), 2.23 (s, 3H), 2.37 (s, 3H), 2.53-2.79 (m, 5H), 3.85-4.07 (m, 5H), 6.95-7.00 (m, 2H), 7.14 (s, 1H), 7.25 (d, 1H, J=4.2 Hz), 8.10 (s, 1H), 8.40 (d, 1H, J=3.7 Hz); 13C NMR (CDCl3) δ 17.90, 18.58, 21.71, 29.04, 29.37, 30.08, 31.25, 43.84, 53.30, 57.64, 60.19, 121.29, 131.51, 133.03, 134.11, 136.25, 138.92, 145.97, 146.88, 158.41, 160.63; ES-MS m/z 410 (M+H). Anal Calcd. For C23H31N5O200.1(H2O)90.3CH2Cl2): C, 64.07; H, 7.34; N, 16.03. Found: C, 64.13; H, 7.44; N, 15.69.

Workup

  1. temperatureat reflux
  2. concentrationconcentrated in vacuo
  3. customPurification by flash chromatography on silica gel
  4. customfollowed by purification by radial chromatography

Sources & evidence

ORD record
ord-f8e3ddd3714542c7a8b63a4f964eb191
Source dataset
uspto-grants-2007_11
Patent number
US07291631B2

Reaction notes

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