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Trimethylsilyl isocyanate → 4-[(3,5-Dimethyl-pyridin-2-ylmethyl)-(3-isopropyl-pyridin-2-ylmethyl)-amino]-piperidine-1-carboxylic acid amide

HRID 251157
Notes
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Reaction equation

HRID 251157 reaction equation
[CH3:1][C:2]1[C:3]([CH2:9][N:10]([CH2:17][C:18]2[C:23]([CH:24]([CH3:26])[CH3:25])=[CH:22][CH:21]=[CH:20][N:19]=2)[CH:11]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1.C[Si]([N:31]=[C:32]=[O:33])(C)C>CC(O)C>[CH3:1][C:2]1[C:3]([CH2:9][N:10]([CH2:17][C:18]2[C:23]([CH:24]([CH3:26])[CH3:25])=[CH:22][CH:21]=[CH:20][N:19]=2)[CH:11]2[CH2:16][CH2:15][N:14]([C:32]([NH2:31])=[O:33])[CH2:13][CH2:12]2)=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

4

Reactant 2

HCID 70696Trimethylsilyl isocyanateHCID 58997074(3,5-Dimethyl-pyridin-2-ylmethyl)-(3-isopropyl-pyridin-2-ylmethyl)-piperidin-4-yl-amine

Product 1

HCID 589970564-[(3,5-Dimethyl-pyridin-2-ylmethyl)-(3-isopropyl-pyridin-2-ylmethyl)-amino]-piperidine-1-carboxylic acid amideYield 73%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

(3,5-Dimethyl-pyridin-2-ylmethyl)-(3-isopropyl-pyridin-2-ylmethyl)-piperidin-4-yl-amine (145 mg, 0.41 mmol) was dissolved in i-PrOH (4 mL) and treated with trimethylsilylisocyanate (78 μL, 0.58 mmol) at room temperature for 16 hours. The solution was then concentrated under reduced pressure and dried in vacuo. The crude material was purified by column chromatography with silica gel (15:1:0.1 CH2Cl2/MeOH/NH4OH) to give COMPOUND 301 as a colorless oil (118 mg, 73%). 1H NMR (CDCl3) δ 0.93 (d, 6H, J=6.6 Hz), 1.66 (q, 2H, J=11.1 Hz), 1.89 (br d, 2H, J=12.3 Hz), 2.17 (s, 3H), 2.28 (s, 3H), 2.68 (br t, 3H, J=12.3 Hz), 2.82 (sept, 1H, J=6.6 Hz), 3.77 (s, 2H), 3.83 (s, 2H), 4.00 (br d, 2H, J=12.6 Hz), 4.45 (br, 2H(NH2)), 7.15 (m, 1H), 7.24 (s, 1H), 7.50 (d, 1H, J=7.2 Hz), 8.19 (s, 1H), 8.32 (d, 1H, J=3.6 Hz). 13C NMR (CDCl3) δ 17.91, 18.07, 23.21 (2C), 26.93 (2C), 27.00, 44.49 (2C), 53.97 (2C), 56.89, 122.79, 131.89, 132.84, 133.47, 138.68, 144.03, 145.03, 146.26, 154.10, 155.91, 157.78. ES-MS m/z 396 (M+H). Anal. Calcd. for C23H33N5O.0.8CH2Cl2: C, 67.39; H, 8.51; N, 17.08. Found: C, 67.33; H, 8.23; N, 17.27.

Workup

  1. concentrationThe solution was then concentrated under reduced pressure
  2. customdried in vacuo
  3. customThe crude material was purified by column chromatography with silica gel (15:1:0.1 CH2Cl2/MeOH/NH4OH)

Sources & evidence

ORD record
ord-7f9915a614f4474aa5ca5dea9ccbff2d
Source dataset
uspto-grants-2011_01
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07863293B2

Reaction notes

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