Ethyl isocyanate → (3-{4-[1-(6-Cyano-pyridin-2-ylmethyl)-3-ethyl-ureido]-piperidin-1-yl}-butyl)-carbamic acid tert-butyl ester

HRID 1711146Notes

Reaction equation

[C:1]([O:5][C:6](=[O:28])[NH:7][CH2:8][CH2:9][CH:10]([N:12]1[CH2:17][CH2:16][CH:15]([NH:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([C:26]#[N:27])[N:21]=2)[CH2:14][CH2:13]1)[CH3:11])([CH3:4])([CH3:3])[CH3:2].[CH2:29]([N:31]=[C:32]=[O:33])[CH3:30]>ClCCCl>[C:1]([O:5][C:6](=[O:28])[NH:7][CH2:8][CH2:9][CH:10]([N:12]1[CH2:13][CH2:14][CH:15]([N:18]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([C:26]#[N:27])[N:21]=2)[C:32]([NH:31][CH2:29][CH3:30])=[O:33])[CH2:16][CH2:17]1)[CH3:11])([CH3:2])([CH3:3])[CH3:4]

Participants

Conditions

Temperature: 55 °C

Procedure

(3-{4-[(6-Cyano-pyridin-2-ylmethyl)-amino]-piperidin-1-yl}-butyl)-carbamic acid tert-butyl ester (0.067 g, 0.17 mmol) and ethyl isocyanate (20 μL, 0.25 mmol) were combined in 1,2-dichloroethane (5 ml) and the resulting mixture was stirred at 55° C. for 16 h. The solvent was removed in vacuo and the crude residue was purified by column chromatography on silica gel (CH2Cl2:MeOH:NH4OH, 93:6:1, v/v/v) to give (3-{4-[1-(6-cyano-pyridin-2-ylmethyl)-3-ethyl-ureido]-piperidin-1-yl}-butyl)-carbamic acid tert-butyl ester (0.075 g, 95%) as a white foam. 1H NMR (CDCl3) δ 0.93 (d, 3H, J=6.0 Hz), 1.12 (t, 3H, J=7.5 Hz), 1.40 (s+m, 13H), 1.65 (m, 1H), 1.92 (m, 2H), 2.18 (br t, 1H, J=9.0 Hz), 2.52 (m, 2H), 2.69-2.85 (m, 3H), 3.09 (m, 1H), 3.21-3.33 (m, 3H), 4.12 (m, 1H), 4.44 (s, 2H), 5.33 (br s, 1H), 5.95 (br s, 1H), 7.57 (d, 1H, J=9.0 Hz), 7.61 (d, 1H, J=9.0 Hz), 7.83 (t, 1H, J=7.5 Hz).

Workup

customThe solvent was removed in vacuo
customthe crude residue was purified by column chromatography on silica gel (CH2Cl2:MeOH:NH4OH, 93:6:1, v/v/v)

Sources & evidence

ORD record: ord-c0f72abd268249be9f358c8583e1f873
Source dataset: uspto-grants-2010_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07790747B2

Reaction notes

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