Phenyl N-hydroxycarbamate → 4-[(5-Chloro-3-methyl-pyridin-2-ylmethyl)-(3-isopropyl-pyridin-2-ylmethyl)-amino]-piperidine-1-carboxylic acid hydroxyamide

HRID 251123Notes

Reaction equation

HRID 251123 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH3:26])[C:5]([CH2:8][N:9]([CH2:16][C:17]2[C:22]([CH:23]([CH3:25])[CH3:24])=[CH:21][CH:20]=[CH:19][N:18]=2)[CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[N:6][CH:7]=1.[O:27]([C:34]([NH:36][OH:37])=O)C1C=CC=CC=1>C1COCC1>[OH:37][NH:36][C:34]([N:13]1[CH2:12][CH2:11][CH:10]([N:9]([CH2:8][C:5]2[C:4]([CH3:26])=[CH:3][C:2]([Cl:1])=[CH:7][N:6]=2)[CH2:16][C:17]2[C:22]([CH:23]([CH3:24])[CH3:25])=[CH:21][CH:20]=[CH:19][N:18]=2)[CH2:15][CH2:14]1)=[O:27]

Participants

4

Reactant 2

HCID 148233Phenyl N-hydroxycarbamateHCID 67272269(5-Chloro-3-methyl-pyridin-2-ylmethyl)-(3-isopropyl-pyridin-2-ylmethyl)-piperidin-4-yl-amine

Product 1

HCID 589969324-[(5-Chloro-3-methyl-pyridin-2-ylmethyl)-(3-isopropyl-pyridin-2-ylmethyl)-amino]-piperidine-1-carboxylic acid hydroxyamideYield 78.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (5-Chloro-3-methyl-pyridin-2-ylmethyl)-(3-isopropyl-pyridin-2-ylmethyl)-piperidin-4-yl-amine (0.263 g, 0.71 mmol) in dry THF (7 mL) was added N-(phenoxycarbonyl)hydroxylamine (0.216 g, 1.41 mmol) and the resultant solution was stirred at 60° C. overnight. The mixture was cooled to room temperature and concentrated. Purification of the crude material by column chromatography on silica gel (10:1:1 CH2Cl2-MeOH—NH4OH) provided 241 mg (64%) of COMPOUND 264 as a white solid. 1H NMR (CDCl3) δ 0.99 (d, 6H, J=6.9 Hz), 1.60-1.66 (m, 2H), 1.92 (d, 2H, J=11.1 Hz), 2.14 (s, 3H), 2.66-2.88 (m, 4H), 3.78 (s, 2H), 3.81 (s, 2H), 4.04 (d, 2H, J=12.9 Hz), 6.65 (br s, 1H), 6.81 (br s, 1H), 7.16 (dd, 1H, J=7.8, 4.8 Hz), 7.42 (d, 1H, J=1.5 Hz), 7.52 (dd, 1H, J=7.8, 1.5 Hz), 8.32-8.34 (m, 2H); 13C NMR (CDCl3) δ 19.64, 24.80, 28.47, 28.74, 45.43, 55.31, 58.83, 124.66, 132.29, 135.42, 136.61, 139.11, 145.69, 146.12, 147.20, 156.93, 162.45; ES-MS m/z 432 (35Cl) & 434 (37Cl) (M+H). Anal. Calcd. For C22H30N5O2Cl.0.2CH2Cl2.0.5H2O: C, 58.22; H, 6.91; N, 15.29; Cl, 10.84. Found: C, 58.51; H, 6.68; N, 15.29; Cl, 10.55.

Workup

  1. concentrationconcentrated
  2. customPurification of the crude material by column chromatography on silica gel (10:1:1 CH2Cl2-MeOH—NH4OH)

Sources & evidence

ORD record
ord-033e3160f40848d6a7c2dd2e604fbcb2
Source dataset
uspto-grants-2011_01
Patent number
US07863293B2

Reaction notes

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