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

HRID 1592543Notes

Reaction equation

HRID 1592543 reaction equation
[CH3:1][C:2]1[C:3]([CH2:9][N:10]([CH:19]2[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)[CH:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)[CH3:12])=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1.C[Si]([N:29]=[C:30]=[O:31])(C)C>CC(O)C>[CH3:1][C:2]1[C:3]([CH2:9][N:10]([CH:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)[CH3:12])[CH:19]2[CH2:20][CH2:21][N:22]([C:30]([NH2:29])=[O:31])[CH2:23][CH2:24]2)=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1

Participants

4

Reactant 2

HCID 70696Trimethylsilyl isocyanateHCID 67271817(3,5-Dimethyl-pyridin-2-ylmethyl)-piperidin-4-yl-(1-pyridin-2-yl-ethyl)-amine

Product 1

HCID 589971304-[(3,5-Dimethyl-pyridin-2-ylmethyl)-(1-pyridin-2-yl-ethyl)-amino]-piperidine-1-carboxylic acid amideYield 90.7%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

To a solution of (3,5-Dimethyl-pyridin-2-ylmethyl)-piperidin-4-yl-(1-pyridin-2-yl-ethyl)-amine (194 mg, 0.60 mmol) in 2-propanol (3 mL) was added trimethylsilyl-isocyanate (85 μL, 0.63 mmol). The resultant solution was stirred at room temperature overnight then concentrated. Purification of the crude material by column chromatography on silica gel (10:1:1 CH2Cl2-MeOH—NH4OH) gave COMPOUND 262 (200 mg, 88%) as a white solid. 1H NMR (CDCl3) δ 0.96-1.02 (m, 1H), 1.45-1.49 (m, 4H), 1.52-1.86 (m, 2H), 2.26 (s, 3H), 2.27 (s, 3H), 2.53-2.62 (m, 1H), 2.71-2.80 (m, 1H), 2.89-2.96 (m, 1H), 3.77-3.97 (m, 5H), 4.37 (s, 2H), 7.10-7.25 (m, 2H), 7.39 (d, 1H, J=7.8 Hz), 7.57-7.62 (m, 1H), 8.19 (br s, 1H), 8.51 (d, 1H-J=3.9 Hz); 13C NMR (CDCl3) δ 13.61, 15.79, 16.16, 27.90, 28.13, 42.22, 42.27, 49.35, 52.87, 55.61, 119.60, 121.54, 129.51, 130.57, 133.80, 136.93, 144.14, 146.25, 152.72, 156.04, 160.52; ES-MS m/z 368 (M+H). Anal. Calcd. For C21H29N5O.0.8H2O: C, 66.05; H, 8.08; N, 18.34. Found: C, 65.9281; H, 7.73; N, 18.18.

Workup

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

Sources & evidence

ORD record
ord-5a66ba262c364bde8d1a2f11ac0f9b18
Source dataset
uspto-grants-2007_11
Patent number
US07291631B2

Reaction notes

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