Benzimidazole → HCID 59803191, compound

HRID 1801597Notes

Reaction equation

[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.Br[C:11]1[CH:12]=[C:13]([CH:24]=[CH:25][C:26]=1[Cl:27])[CH2:14][NH:15][C@@H:16]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH3:17].C(=O)([O-])[O-].[K+].[K+]>[Cu]I.CN1C(=O)CCC1>[N:1]1([C:11]2[CH:12]=[C:13]([CH:24]=[CH:25][C:26]=2[Cl:27])[CH2:14][NH:15][C@@H:16]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH3:17])[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1

Participants

Conditions

Temperature: 150 °C

Procedure

To a mixture of 1H-benzo[d]imidazole (0.106 g, 0.90 mmol) and (R)—N-(3-bromo-4-chlorobenzyl)-1-phenylethanamine 75 (0.247 g, 0.76 mmol) was added potassium carbonate (0.141 g, 1.0 mmol), copper(I) iodide (0.023 g, 0.12 mmol), and NMP (0.8 mL). The reaction mixture was degassed and heated to 150° C. for 3 d, diluted with EtOAc, filtered, and concentrated in vacuo. Purification by flash column chromatography on silica gel (eluted with 40% to 100% EtOAc in hexanes) gave (1R)—N-(3-(1H-benzo[d]imidazol-1-yl)-4-chlorobenzyl)-1-phenylethanamine 76 (0.053 g, 19% yield) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 1.38 (d, J=6.7 Hz, 3H), 3.69 (s, 2H), 3.82 (q, J=6.7 Hz, 1H), 7.20-7.43 (m, 11H), 7.55 (d, J=8.2 Hz, 1H), 7.79 (d, J=7.2 Hz, 1H), 8.04 (s, 1H). Mass spectrum: calculated for C22H20ClN3 361.1. found 362.2 (M++1).

Workup

customThe reaction mixture was degassed
additiondiluted with EtOAc
filtrationfiltered
concentrationconcentrated in vacuo
customPurification by flash column chromatography on silica gel (eluted with 40% to 100% EtOAc in hexanes)

Sources & evidence

ORD record: ord-aa9c42ae833f4e3d9e6d551d869c0b6b
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08349831B2

Reaction notes

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