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

HRID 251161Notes

Reaction equation

HRID 251161 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH3:27])[C:5]([CH2:8][N:9]([CH2:16][C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[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:28]([C:35]([NH:37][OH:38])=O)C1C=CC=CC=1>C1COCC1>[OH:38][NH:37][C:35]([N:13]1[CH2:14][CH2:15][CH:10]([N:9]([CH2:8][C:5]2[C:4]([CH3:27])=[CH:3][C:2]([Cl:1])=[CH:7][N:6]=2)[CH2:16][C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH:20]=[CH:19][N:18]=2)[CH2:11][CH2:12]1)=[O:28]

Participants

4

Reactant 2

HCID 148233Phenyl N-hydroxycarbamateHCID 67272447(5-Chloro-3-methyl-pyridin-2-ylmethyl)-isoquinolin-1-ylmethyl-piperidine-4-yl-amine

Product 1

HCID 589970224-[(5-Chloro-3-methyl-pyridin-2-ylmethyl)-isoquinolin-1-ylmethyl-amino]-piperidine-1-carboxylic acid hydroxyamideYield 51%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (5-Chloro-3-methyl-pyridin-2-ylmethyl)-isoquinolin-1-ylmethyl-piperidine-4-yl-amine (140 mg, 0.37 mmol) and N-(phenoxycarbonyl)hydroxylamine (112 mg, 0.74 mmol) in anhydrous THF (4 mL) was stirred for 16 hours at 70° C. The solution was then cooled and concentrated under reduced pressure and dried in vacuo. The crude material was purified by column chromatography with silica gel (50:1:0.1 CH2Cl2/MeOH/NH4OH) to give COMPOUND 308 as a white solid (82 mg, 51%). 1H NMR (CDCl3): δ 1.73 (q, 2H, J=11.1 Hz), 1.96 (s, 3H), 1.99 (br, 2H), 2.70 (br, 3H), 3.85 (s, 2H), 4.05 (d, 2H, J=13.2 Hz), 4.26 (s, 2H), 6.65 (br, 1H(OH)), 6.81 (br s, 1H(NH)), 7.33 (s, 1H), 7.42 (t, 1H, J=7.2 Hz), 7.54 (d, 1H, J=4.8 Hz), 7.62 (t, 1H, J=7.8 Hz), 7.77 (d, 1H, J=7.8 Hz), 7.95 (d, 1H, J=7.2 Hz), 8.26 (s, 1H), 8.39 (d, 1H, J=3.6 Hz). 13C NMR (CDCl3) δ 18.75, 28.62 (2C), 45.17 (2C), 56.17, 56.61, 61.23, 122.76, 127.88, 128.44, 128.59, 129.29, 132.10, 132.65, 137.35, 138.33, 139.35, 141.74, 145.51, 156.93, 160.35, 162.80. ES-MS m/z 441 (M+H). Anal. Calcd. for C23H26N5O2Cl.0.2H2O: C, 62.28; H, 6.00; N, 15.79; Cl, 7.99. Found: C, 62.31; H, 5.83; N, 15.50; Cl, 8.06.

Workup

  1. temperatureThe solution was then cooled
  2. concentrationconcentrated under reduced pressure
  3. customdried in vacuo
  4. customThe crude material was purified by column chromatography with silica gel (50:1:0.1 CH2Cl2/MeOH/NH4OH)

Sources & evidence

ORD record
ord-6ae9481925af41daac236472b85771fb
Source dataset
uspto-grants-2011_01
Patent number
US07863293B2

Reaction notes

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