Phenyl N-hydroxycarbamate → 4-[(1H-Benzoimidazol-4-ylmethyl)-(3-methyl-pyridin-2-ylmethyl)-amino]-piperidine-1-carboxylic acid hydroxyamide

HRID 251149Notes

Reaction equation

HRID 251149 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[C:9]([CH2:10][N:11]([CH2:18][C:19]3[C:24]([CH3:25])=[CH:23][CH:22]=[CH:21][N:20]=3)[CH:12]3[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]3)[C:4]=2[N:3]=[CH:2]1.[O:26]([C:33]([NH:35][OH:36])=O)C1C=CC=CC=1>C1COCC1>[OH:36][NH:35][C:33]([N:15]1[CH2:14][CH2:13][CH:12]([N:11]([CH2:10][C:9]2[C:4]3[N:3]=[CH:2][NH:1][C:5]=3[CH:6]=[CH:7][CH:8]=2)[CH2:18][C:19]2[C:24]([CH3:25])=[CH:23][CH:22]=[CH:21][N:20]=2)[CH2:17][CH2:16]1)=[O:26]

Participants

4

Reactant 2

HCID 148233Phenyl N-hydroxycarbamateHCID 67273179(1H-Benzoimidazol-4-ylmethyl)-(3-methyl-pyridin-2-ylmethyl)-piperidin-4-yl-amine

Product 1

HCID 589970024-[(1H-Benzoimidazol-4-ylmethyl)-(3-methyl-pyridin-2-ylmethyl)-amino]-piperidine-1-carboxylic acid hydroxyamideYield 55%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a THF solution (3 mL) of the amine from above (100 mg, 0.300 mmol) was added N-(Phenoxycarbonyl)hydroxylamine (54.8 mg, 0.360 mmol), and the resultant solution was heated to 80° C. for 7 h and stirred at room temperature for 66 h. The solution was concentrated to dryness and the crude material was purified by flash chromatography on silica gel (CH2Cl2/MeOH/NH4OH, 80:10:10) to afford COMPOUND 288 (49 mg, 55%) as a white solid. 1H NMR (CDCl3) δ 1.36-1.55 (m, 2H), 1.75 (d, 2H, J=11.7 Hz), 2.34 (s, 3H), 2.50-2.74 (m, 3H), 3.92 (s, 2H), 3.95 (d, 2H, J=15 Hz), 4.02 (s, 2H), 6.83 (br s, 1H), 7.04 (d, 1H, J=7.2 Hz), 7.11-7.23 (m, 2H), 7.52 (d, 1H, J=7.2 Hz), 7.74 (d, 1H, J=7.8 Hz), 8.18 (s, 1H), 8.53 (d, 1H, J=4.5 Hz); 13C NMR (CDCl3) δ 18.78, 27.46, 43.88, 52.09, 53.87, 54.58, 56.25, 118.67, 121.91, 122.15, 122.64, 124.55, 132.19, 133.51, 139.04, 141.08, 143.03, 145.87, 157.78, 161.25; ES-MS m/z 395 (M+H). Anal. Calcd. for C21H26N6O.0.5H2O.0.2 CH2Cl2: C, 58.76; H, 6.41; N, 19.21. Found: C, 58.65; H, 6.36; N, 19.19.

Workup

  1. concentrationThe solution was concentrated to dryness
  2. customthe crude material was purified by flash chromatography on silica gel (CH2Cl2/MeOH/NH4OH, 80:10:10)

Sources & evidence

ORD record
ord-cf63662183294e799c45159dfc37481a
Source dataset
uspto-grants-2011_01
Patent number
US07863293B2

Reaction notes

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