N-Methylaniline → tert-Butyl {2-[4-(methyl-phenyl-carbamoyl)-butylsulfanyl]-benzoimidazol-1-yl}-acetate

HRID 2389475Notes

Reaction equation

HRID 2389475 reaction equation
Br[CH2:2][CH2:3][CH2:4][CH2:5][C:6](Cl)=[O:7].C([O-])([O-])=O.[K+].[K+].[CH3:15][NH:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[SH:23][C:24]1[N:28]([CH2:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[C:27]2[CH:37]=[CH:38][CH:39]=[CH:40][C:26]=2[N:25]=1>C(#N)C>[CH3:15][N:16]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:6]([CH2:5][CH2:4][CH2:3][CH2:2][S:23][C:24]1[N:28]([CH2:29][C:30]([O:32][C:33]([CH3:35])([CH3:36])[CH3:34])=[O:31])[C:27]2[CH:37]=[CH:38][CH:39]=[CH:40][C:26]=2[N:25]=1)=[O:7]

Participants

6

Reactant 4

HCID 7515N-MethylanilineHCID 11430Potassium CarbonateHCID 5211735-Bromovaleryl chlorideHCID 178451223HCID 178451223, compound

Product 1

HCID 86620025tert-Butyl {2-[4-(methyl-phenyl-carbamoyl)-butylsulfanyl]-benzoimidazol-1-yl}-acetateYield 77%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a suspension of 5-bromovaleryl chloride (24.8 mg, 16.6 μl, 0.12 mmol) and K2CO3 (31.2 mg, 0.23 mmol) in acetonitrile (3 ml) is added N-methylaniline (14.5 mg, 14.7 μl, 0.14 mmol). After 1 h of stirring, tert-butyl (2-mercapto-benzoimidazol-1-yl)-acetate (Intermediate 3-I, 30 mg, 0.11 mmol) is added and the resulting mixture is refluxed overnight. The crude suspension is filtered over a fritted funnel and the solvent evaporated in vacuo. The crude yellow oil is purified by flash-chromatography on silica gel (AcOEt/heptane, 2:1 containing 3% of Et3N), yielding the title compound (38.4 mg) in 75% as a yellowish oil: tR=6.84 min (LC-1), ESI-MS (pos.): m/z 455.46 [M+H]+, ESI-MS (neg.): m/z 452.19 [M−H]+; 1H-NMR (DMSO-d6): δ (ppm) 1.38 (s, 9H, tBu), 1.56 (m, 4H, CH2CH2), 2.03 (m, 2H, CH2C═O), 3.17 (m, 2H, SCH2), 3.31 (s, 3H, NMe), 4.92 (s, 2H, CH2CO2), 7.12-7.16 (m, 2Harom), 7.26-7.30 (m, 3Harom), 7.36-7.46 (m, 3Harom), 7.51 (m, 1Harom).

Workup

  1. temperaturethe resulting mixture is refluxed overnight
  2. filtrationThe crude suspension is filtered over a fritted funnel
  3. customthe solvent evaporated in vacuo
  4. customThe crude yellow oil is purified by flash-chromatography on silica gel (AcOEt/heptane, 2:1 containing 3% of Et3N)

Sources & evidence

ORD record
ord-ef08ea5ef1f140d7b0df2d35f4a31b96
Source dataset
uspto-grants-2012_09
Patent number
US08273740B2

Reaction notes

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