Methyl Isocyanate → n-(1-{5-[5-(4-Isopropoxyphenoxy)-1,3,4-thiadiazol-2-yl]thien-2-yl}ethyl)-n'-methylurea

HRID 404903Notes

Reaction equation

[CH:1]([O:4][C:5]1[CH:24]=[CH:23][C:8]([O:9][C:10]2[S:14][C:13]([C:15]3[S:19][C:18]([CH:20]([NH2:22])[CH3:21])=[CH:17][CH:16]=3)=[N:12][N:11]=2)=[CH:7][CH:6]=1)([CH3:3])[CH3:2].[CH3:25][N:26]=[C:27]=[O:28]>C(Cl)Cl>[CH:1]([O:4][C:5]1[CH:24]=[CH:23][C:8]([O:9][C:10]2[S:14][C:13]([C:15]3[S:19][C:18]([CH:20]([NH:22][C:27]([NH:26][CH3:25])=[O:28])[CH3:21])=[CH:17][CH:16]=3)=[N:12][N:11]=2)=[CH:7][CH:6]=1)([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 25 °C

Procedure

A solution of Example 24G (0.044 g, 0.122 mmol) in CH2Cl2 (2 mL) was treated with methyl isocyanate (0.035 g, 0.61 mmol). The reaction was stirred at 25° C. for 1 hour and was concentrated under reduced pressure on a rotary evaporator. The residual white solids (0.046 g) were purified by flash chromatography on silica gel eluting with a solvent gradient from 50% to 70% ethyl acetate in hexanes to provide 0.025 g (49%) of the title compound as a white solid, 1H NMR (300 MHz, DMSO-d6) δ ppm 7.48 (d, J=3.68 Hz, 1H) 7.39 (d, J=9.19 Hz, 2H) 7.02 (d, J=9.19 Hz, 2H) 6.96 (dd, J=3.86, 0.92 Hz, 1H) 6.53 (d, J=8.09 Hz, 1H) 5.75 (q, J=4.78 Hz, 1H) 4.94-5.05 (m, 1H) 4.63 (heptet, J=5.88 Hz, 1H) 2.56 (d, J=4.78 Hz, 3H) 1.42 (d, J=6.99 Hz, 3H) 1.28 (d, J=5.88 Hz, 6H); MS (ESI) m/z 419 (M+H+.

Workup

concentrationwas concentrated under reduced pressure on a rotary evaporator
customThe residual white solids (0.046 g) were purified by flash chromatography on silica gel eluting with a solvent gradient from 50% to 70% ethyl acetate in hexanes

Sources & evidence

ORD record: ord-eabaeba5b02a466286063c9cb2daed78
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08748627B2

Reaction notes

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