2-Methoxyphenyl Isothiocyanate → N-[1-(Cyclopropylmethyl)-2-(4-ethoxybenzyl)-1H-benzimidazol-5-yl]-N'-(2-methoxyphenyl)-N-methylthiourea

HRID 1796491Notes

Reaction equation

[N:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[O:10][CH3:11])=[C:2]=[S:3].[CH:12]1([CH2:15][N:16]2[C:20]3[CH:21]=[CH:22][C:23]([NH:25][CH3:26])=[CH:24][C:19]=3[N:18]=[C:17]2[CH2:27][C:28]2[CH:33]=[CH:32][C:31]([O:34][CH2:35][CH3:36])=[CH:30][CH:29]=2)[CH2:14][CH2:13]1>CN(C=O)C>[CH:12]1([CH2:15][N:16]2[C:20]3[CH:21]=[CH:22][C:23]([N:25]([CH3:26])[C:2]([NH:1][C:4]4[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=4[O:10][CH3:11])=[S:3])=[CH:24][C:19]=3[N:18]=[C:17]2[CH2:27][C:28]2[CH:29]=[CH:30][C:31]([O:34][CH2:35][CH3:36])=[CH:32][CH:33]=2)[CH2:14][CH2:13]1

Participants

Conditions

Temperature: 50 °C

Procedure

1-Isothiocyanato-2-methoxybenzene (100 mg, 0.61 mmol) was added to a solution of 1-(cyclopropylmethyl)-2-(4-ethoxybenzyl)-N-methyl-1H-benzimidazol-5-amine (100 mmol, 0.30 mmol) in DMF (5 mL). The reaction mixture was heated at 50° C. overnight. The crude product isolated following removal of the solvent was purified by chromatography on silica gel (EtOAc/CH2Cl2 1:1) giving the desired product (85 mg, 57%) 1HNMR (CDCl3): free base δ 8.26 (dd, J=2.0, 8.4 Hz, 1H), 7.74 (d, J=2.0 Hz, 1H), 7.50 (s, 1H), 7.43 (d, J=8.4 Hz, 1H), 7.20 (dd, J=1.6, 8.4 Hz, 1H), 7.15 (d, J=8.4 Hz, 2H), 7.08–7.02 (m, 1H), 6.98–6.92 (m, 1H), 6.83 (d, J=8.4 Hz, 2H), 6.75 (d, J=8.4 Hz, 1H), 4.29 (s, 2H), 4.00 (q, J=7.0 Hz, 2H), 3.96 (d, J=6.8 Hz, 2H), 3.80 (s, 3H), 3.58 (s, 3H), 1.37 (t, J=7.0 Hz, 3H), 1.10–1.00 (m, 1H), 0.59–0.52 (m, 2H), 0.32–0.25 (m, 2H). MS (ESI) (M+H)+=501.

Workup

customThe crude product isolated
customremoval of the solvent
customwas purified by chromatography on silica gel (EtOAc/CH2Cl2 1:1)

Sources & evidence

ORD record: ord-097af48fb6994334aa0e1f828ac0df6b
Source dataset: uspto-grants-2006_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07030139B2

Reaction notes

Loading…